Cardiology Guide

9WhZ_ebe]o=k_Z[
&DUGLRORJ\*XLGH
,1',$
,1',$
CIMS®
Cardiology Guide
Publisher of CIMS/IDR Chief Executive Officer - MIMS Group

Masaki Takahata
CIMS Medica India Pvt. Ltd.
Business Director - India
(Previously known as UBM Medica India Pvt Ltd.)
Joe Thomas
Registered Office:
Margosa Building, #2,13th Cross, Margosa Road, Scientific Content Layout & Design
Malleshwaram, Bangalore - 560 003 Anarghya Arun Kharkwal
Ph: +91-80-4346 4500; Fax: +91-80-4346 45230 Nikki Ng Rashmi Suresh
Sahana S Sivaramakrishnan R
Corporate Office: Shashirekha D
Umesh MC Business Queries
Boomerang (Kanakia Spaces), Wing-B1, #403, Chandiwali
West & South Zone
Farm Road, Chandiwali, Powai, Mumbai - 400 072 Information Systems Ninad Virale
Ph: +91-22-6612 2600; Fax: +91-22-6612 2626 India Prateek Pandey
Ashutosh Mishra
Regional Office:
Production & Logistics
#709, 7th Floor, Devika Tower, Singapore
Swapnil Vichare
Nehru Place, New Dlehi- 110 019 Shannen Ng
Tel: +91-11-4285 4300; Fax: +91-11-4285 4310 Subscription Queries & Book Sales
E-mail: enquiry.in@cims.co.in Naren Tamang +91-9717173989
URL: www.cimsasia.com Anisha Nagpal +91-8169864404
For all India advertisement enquiry
contact our centralized number
+91-22-66122600
E-mail: enquiry.in@cims.co.in
CIMS Cardiology Guide provides detailed prescribing information covering

management of cardiometabolic diseases.
Editorial matter published herein is prepared by our own professional
editorial staff. Although great effort has been made in compiling and
checking the information contained in CIMS Cardiology Guide to ensure
that they are accurate; the authors, publishers, and editors shall not be
responsible or in any way liable for any errors, omissions or inaccuracies
in this publication whether arising from negligence or otherwise howsoever
or for any consequences arising therefrom. The inclusion or exclusion of
any product name either in text or visual does not mean that the publisher
advocates or rejects its use either generally or in any particular field/s.
The publisher, authors and editors also expressly disclaim any and all
Drug References Worldwide liability to any person whosoever in respect of any loss, damage, death,
.................................................................................... personal injury or other consequences whatsoever, howsoever caused or
arising, suffered by any such person by their use or reliance upon, in any
MIMS – Australia, China, Hong Kong, Indonesia,
way, the information contained in this publication.
Korea, Malaysia, Myanmar, New Zealand, Philippines,
Singapore, Thailand, Vietnam Advertisements are subject to editorial acceptance and have no influence
on editorial content or presentation.
CIMS, IDR Tripple i – India
Affiliation Nil. CIMS Medica India Pvt. Ltd. is an independent publisher
and is not affiliated with any pharmaceutical manufacturer or professional
association.
© 2022 CIMS Medica India Pvt. Ltd. (Previously known as UBM Medica
India Pvt. Ltd.) All rights reserved. No portion of this publication may be
reproduced in any language, stored in or introduced into a retrieval system,
or transmitted, in any form or by any means (electronic, electrostatic,
magnetic tape, mechanical, photocopying, recording or otherwise), without
the prior written permission of the publisher.
HONORARY EDITORIAL
FOREWORD
ADVISORY BOARD - ASIA
Malaysia
In the tradition of providing focused information to • Dr Jeyamalar Rajadurai
specialists, we proudly present to you CIMS Cardiology MBBS (Mal), MRCP (UK), FRCP (Lond), FACC, FESC,
FNHAM, FASCC
Guide. This new guide is designed specifically to cater Consultant Cardiologist
Subang Jaya Medical Centre
to the needs of physicians who treat common
• Dato’ Dr Tamil Selvan Muthusamy
cardiometabolic disorders. MBBS (Malaya), MRCP (UK), CCST Cardiology (UK)
Consultant Cardiologist
Cardiac Vascular Sentral Kuala Lumpur (CVSKL)
CIMS Cardiology Guide contains disease management • Dr David Choon Siew Kit
MBChB (UK), FRCS (England), FAMM
guidelines, a collection of up-to-date information on Department of Orthopaedic Surgery
general guidelines on diagnosis of cardiometabolic University Malaya Specialist Centre
• Datuk Dr Yunus Gul Bin Alif Gul
diseases and detailed charts on its management. MBBCh (Ireland), BAO, LRCPI, LRCSI, FRCS (Gen Surg)
These guidelines shall provide clarity, and delves into Consultant, General & Gastrointestinal Surgery
Prince Court Medical Centre
specific cardiovascular disorders with detailed
descriptions that range from aetiology and Hong Kong
pathophysiology to evidence informed approaches to • Dr Andy Wai-Kwong Chan
diagnosis and management. We have sourced global MBBS (HK), MRCP (UK), FRCP (Lond),
FRCP (Edin), FRCP (Glasg), FRCP (Irel), FHKCP,
guidelines such as AHA/ACC, ESC, ACCP, ACCF/ FHKAM (Med), FACC
AHA, ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS, Honorary Consultant (Cardiology)
Department of Medicine and Geriatrics,
WHO to develop the same. United Christian Hospital
Clinical Associate Professor (Honorary) in
Family Medicine
With all these features, we believe that you will find The Chinese University of Hong Kong
Honorary Secretary, Hong Kong College of Cardiology
CIMS Cardiology Guide guide a helpful and highly • Hon Prof Chu-Pak Lau
indispensable reference, as with all the products of MD, MBBS, FRCP, FRACP, FHKAM (Medicine), FHKCP
Specialist in Cardiology
CIMS Medica–A flagship of quality and excellence. Honorary Clinical Professor
Department of Medicine
The University of Hong Kong
Should there be any concern or suggestion you wish • Prof Hung-Fat Tse
MBBS, MD, PhD, FRCP (Edin, Glasg, Lond), FHKCP,
to convey to us in improving the quality and integrity FHKAM (Med), FACC, FESC
of CIMS Cardiology Guide, please feel free to inform Professor, Chair of Cardiovascular Medicine
William MW Mong Professor in Cardiology
our office via phone, fax or mail and let us know your Chief of Cardiology Division, Department of Medicine
thoughts and opinions. Queen Mary Hospital
The University of Hong Kong
• Dr Wong Kwok Yiu, Chris
MBChB, MRCP (UK), FHKAM (Med), FHKCP,
We hope that you find our CIMS Cardiology Guide very FRCP (Edin), FRCP (Glasg)
useful, practical and convenient. President
Hong Kong College of Cardiology
• Prof KS Woo
MBBS (HK), MD, FRACP, FACC, FRCP, FHKAM, FHKCP
Adjunct Professor, Institution of Future Cities
The Chinese University of Hong Kong
Specialist in Cardiology
Union Hospital
• Professor Yu Cheuk Man
MBChB, MRCP (UK), FRACP, FHKCP, FHKAM (Med),
FRCP (Lond), MD
Chairman, Department of Medicine & Therapeutics
The Chinese University of Hong Kong
Head, Division of Cardiology, Prince of Wales Hospital
Indonesia
• Dr Anna Ulfah Rahajoe, SpJP(K), FIHA, FESC,
FACC, FAsCC
President, Indonesian Heart Association (PERKI)
National Cardiovascular Center Harapan Kita
• Dr Aulia Sani, SpJP(K), FJCC, FIHA, FAsCC
HONORARY EDITORIAL CONTENTS
ADVISORY BOARD - ASIA
• Prof Dr Harmani Kalim, MPH, SpJP(K) DISEASE MANAGEMENT CHARTS
Senior Consultant Cardiologist
• Prof Dr H Jusuf Misbach, SpS(K), FAAN
President, Indonesian Neurological
Association (PERDOSSI) Acute Coronary Syndrome...................................... 1
Department of Neurology, Faculty of Medicine
Dr Cipto Mangunkusumo General Hospital
• Dr Pradana Soewondo, SpPD-KEMD Cardiovascular Disease Prevention...................... 31
President, Indonesian Society of
Endocrinology (PERKENI)
Department of Internal Medicine, Metabolic
Endocrinology Division, Faculty of Medicine Chronic Coronary Syndrome................................. 46
Dr Cipto Mangunkusumo General Hospital
• Dr Santoso Karo Karo, MPH, SpJP(K)
Consultant Cardiologist Dyslipidemia ......................................................... 78
• Prof Dr Slamet Suyono, SpPD-KEMD
Senior Consultant Endocrinologist Heart Failure – Acute........................................... 102
Department of Internal Medicine, Metabolic
Endocrinology Division, Faculty of Medicine
Dr Cipto Mangunkusumo General Hospital Heart Failure – Chronic....................................... 129
Philippines
• Dr Nelson S. Abelardo
MD, FPCP, FPCC Hypertension....................................................... 158
Professor of Medicine and Cardiology, College of
Medicine
University of the Philippines – Philippine General Hospital
Diplomate in Internal Medicine and Adult Cardiology
Ischemic stroke.................................................... 188
Chief of Cardiology, Manila Doctors Hospital
• Dr Erlyn C. Demerre
MD, FPCP, FPCC MI w/ ST-segment elevation................................ 206
Diplomate in Internal Medicine and Adult Cardiology and
Echocardiography
St. Luke’s Medical Center, Philippine Heart Center,
Cardinal Santos Medical Center
Venous Thromboembolism – Management ........ 232
• Dr Ma Paz Mildred F. Luque
MD, FPCP, FPCC
Diplomate in Internal Medicine and Adult Cardiology Venous Thromboembolism – Prevention............. 253
Specialist in Cardiac Rehabilitation
St. Luke’s Medical Center, Quezon City and Global City
Singapore
References.......................................................... 270
• Dr Bernard Ee
MBBS, MMed (Int Med), FRCP (Lond), FACC
Gleneagles Medical Center
• Dr Lim Yean Teng
MBBS, MMed (Int Med), MRCP (UK), FAMS (Cardiology),
FRCP (Edin), FACC, FSCAI
Mount Elizabeth Medical Centre
Thailand
• A/Prof Dr. Peera Buranakitjaroen
MD, MSC (Lond), D.Phil (Oxford)
Department of Medicine
Siriraj Hospital
• Prof Nithi Mahanonda
Associate Director
Bangkok Hospital Institute
Vietnam
• Prof Pham Gia Khai
MD, FACC, FESC, FrSc, FAFC
Honorary President, Vietnam Heart Association
Senior Lecturer, Hanoi Medical University
Senior Consultant, Vietnam Heart Institute - Bach Mai
Hospital
ABBREVIATION INDEX
2-D echo 2-dimensional transthoracic HF heart failure pCO2 partial pressure of carbon
echocardiography HFS hip fracture surgery dioxide
3-KAT 3-ketoacyl-CoA thiolase HIT heparin-induced PE pulmonary embolism
A-fib atrial fibrillation thrombocytopenia PEG percutaneous endoscopic
AAA abdominal aortic aneurysm HR heart rate gastrostomy
ABC airway, breathing, IABCP intra-aortic balloon PET positron emission
circulation counterpulsation tomography
ABI ankle-brachial index IART intraatrial reentrant PH pulmonary hypertension
ACEI angiotensin-converting pO2 partial pressure of oxygen
tachycardia
enzyme inhibitors IC intermittent claudication PT prothrombin time
ACS acute coronary syndromes ICD implantable cardioverter PTCA percutaneous transluminal
ALI acute limb ischemia coronary angioplasty
defibrillator
ALP alkaline phosphatase PTT partial thromboplastin time
ICH intracerebral hemorrhage
ALT alanine aminotransferase PVD peripheral vascular disease
AMI acute myocardial infarction ICP intracranial pressure
IE infective endocarditis PVE prosthetic valve
aPTT activated partial
IPC intermittent pneumatic endocarditis
thromboplastin time PVOD pulmonary veno-occlusive
AVNRT atrioventricular node compression
ISA intrinsic sympathomimetic disease
reentry tachycardia PVR pulmonary vascular
AVRT atrioventricular reentrant activity
IST inappropriate sinus resistance
tachycardia r-PA reteplase
BC blood culture tachycardia
IVC inferior vena cava RH right heart
BNP brain natriuretic peptide
IVDA intravenous drug abuser rt-PA recombinant tissue
BPP biophysical profile
CBC complete blood count JNC 7 7th Report of the Joint plasminogen activator
CCD clinical cardiovascular RR respiratory rate
National Committee
RV right ventricle
disease JNC 8 8th Report of the Joint
SANRT sinoatrial nodal reentrant
CCU cardiac care unit National Committee
CK-MB creatine kinase-myocardial tachycardia
JVP jugular venous pressure
SaO2 arterial oxygen
band LAD left anterior descending
CLI critical limb ischemia LBBB left-bundle branch block concentration
CPK creatine phosphokinase LFT liver function test(s) SBP systolic blood pressure
CPP cerebral perfusion pressure LVEF left ventricular ejection sCT spiral computed
CRF chronic renal failure fraction tomography
CRP C-reactive protein SF-36Q medical outcomes short
LVH left ventricular hypertrophy
CT computed tomography MAP mean arterial pressure form 36 questionnaire
CTEPH chronic thromboembolic MDS monophasic dampedsine SOB shortness of breath
pulmonary hypertension MIC minimum inhibitory SPECT single-photon emission CT
CTPA computed tomographic STEMI ST-segment elevation
concentration
pulmonary angiography MPAP mean pulmonary arterial myocardial infarction
CVP central venous pressure SVT supraventricular
pressure
DBP diastolic blood pressure tachycardia
MRA magnetic resonance
DHA docosahexaenoic acid t-PA tissue plasminogen
DIC disseminated intravascular angiography
activator
coagulation MSA membrane stabilizing
TC total cholesterol
ED emergency department activity TEE transesophageal
EF ejection fraction MSSA Methicillin-susceptible
echocardiogram
EPS electrophysiological study Staphylococcus aureus TG triglyceride(s)
FB foreign body N/V nausea/vomiting THR total hip replacement
FBAO foreign body airway NBTV nonbacterial thrombotic TIA transient ischemic attack
obstruction vegetation TNK-tPA tenecteplase
GECS graduated elastic NG nasogastric TOD target organ damage
compression stockings NMTT N-methylthiotetrazole TTE transthoracic
GP glycoprotein NOAC novel oral anticoagulant echocardiography
HACEK Haemophilus NSTEMI non ST-elevation UA unstable angina
parainfluenzae, aprophilus, myocardial infarction UFH unfractionated heparin
& paraphrophilus; NST non-stress test US ultrasonography
Actinobacillus NVE native valve endocarditis VF ventricular fibrillation
actinomycetemcomitans, NYHA New York Heart Association VKA vitamin K antagonists
PAD peripheral arterial disease vs versus
Cardiobacterium hominis,
PAl-1 plasminogen activator-1 VT ventricular tachycardia
Eikenella corrodens, & PaO2 partial arterial pressure of VTE venous thromboembolism
Kingella sp oxygen WIQ walking impairment
Hct hematocrit questionnaire
PCI percutaneous coronary
HDL-C high-density lipoprotein WHO World Heath Organization
intervention
cholesterol
Acute Coronary Syndromes w/out
Persistent ST-Segment Elevation (1 of 30)
1
Patient presents w/ ischemic-type chest discomfort
Pre-hospital & Emergency Department management includes:

• Activate EMS (Emergency Medical Services) system
• 12-lead ECG
• Administer O2: 3-4 L/min if O2 sat <90%
• Aspirin*: 150-300 mg chew & swallow
• Nitrate: 1-3 doses of sublingual Glyceryl trinitrate (GTN) or Isosorbide dinitrate
(ISDN); IV if pain continues
• Opioid (IV): 1-5 mg Morphine if pain continues
• Cardiac biomarkers (Troponins, CK-MB)
• Rest if related to effort
• Standby for resuscitation if needed
2
DIAGNOSIS
Is UA/NSTEMI
Initial ECG & cardiac or STEMI ECG reveals
markers are non-diagnostic suggested? ST-segment
elevation myocardial
infarction (STEMI)
Unstable angina (UA)/Non-ST-
segment elevation myocardial
3 infarction (NSTEMI) is confirmed
REPEAT TESTS Yes TREATMENT
UA/NSTEMI Please see Myocardial
Do results or ongoing chest
is confirmed Infarction w/ ST-
pain suggest UA/
Segment Elevation
NSTEMI?
disease management
chart for further
information
No
Diagnosis is
still uncertain
4 FURTHER TESTING 5
EVALUATION Intermediate-,
Low-risk Is patient at low, High- or Very
patients intermediate, high or high-risk
very high risk for patients
death or MI?
TREATMENT TREATMENT
Continued on Continued on
next page next page
*For patients w/ hypersensitivity or major GI intolerance to Aspirin, may give Clopidogrel, Ticagrelor or Prasugrel.
Not all products are available or approved for above use in all countries.
B1
Acute Coronary Syndromes w/out Persistent ST-Segment Elevation (2 of 30)
PATIENTS WITH CONFIRMED UA/NSTEMI

ACS
5
EVALUATION
Is patient at low, intermediate,
high or very high risk
Low-risk for death or MI? Intermediate-, High- or
patients Very high-risk patients
3 ACUTE TREATMENT
A Pharmacological therapy
REPEAT DIAGNOSTIC TESTS • Antiplatelet therapy:
(IF INDICATED) - Aspirin (if not yet given) plus any of the following
• 2nd troponin measurement should be [dual antiplatelet therapy (DAPT)]:
taken within 3-6 hours after symptom - Ticagrelor
onset if initial test is negative - Prasugrel1
• Monitor for new ECG changes - Clopidogrel2
- Glycoprotein IIb/IIIa inhibitor (Tirofiban or Eptifibatide)
may be considered
• Anticoagulant therapy
- Fondaparinux or
- Low-molecular-weight Heparin (LMWH) or
5 - Unfractionated Heparin (UFH) or
- Direct thrombin inhibitor (Bivalirudin)
EVALUATION • Antianginal agents (as indicated)
Has the patient Yes - Beta-blocker
developed high- - Nitrate
risk criteria? - Calcium antagonist
• High-intensity statin
B Supportive therapy
No
7
6 INVASIVE
STRATEGIES
STRESS TEST Yes Is invasive therapy to No
• Consider conservative be performed?
management without
angiography in low-risk 7 INVASIVE STRATEGIES
patients • Coronary angiography
• Revascularization
A Continue antiplatelet therapy A Continue anti-

• Aspirin plus any of the following: platelet therapy
- Ticagrelor4
- Prasugrel
- Clopidogrel4
- Cangrelor5
• Glycoprotein IIb/IIIa inhibitor3
LONG-
TERM
TREATMENT
1Use of Aspirin & Prasugrel is only recommended for P2Y12 inhibitor-naive patients undergoing PCI.
2If
See next page
risk of bleeding is high, use Aspirin & Clopidogrel.
3May be considered in patients post-PCI if there is a significant amount or size of thrombus seen.
4 If risk of bleeding is high, use Aspirin & Ticagrelor or Aspirin & Clopidogrel.
5May be considered in P2Y inhibitor-naive patients at time of PCI.
12
B2
LONG-TERM (OUTPATIENT) TREATMENT
ACS
C Patient & caregiver education A Pharmacological therapy
D Risk factor management • Antiplatelet agents
• Smoking cessation - Aspirin plus any of the following:
- Ticagrelor/Prasugrel/Clopidogrel
• BP control
• Beta-blocker
• Lipid management
• Fondaparinux/Enoxaparin* for 3-8 days or UFH for 3 days
• Diabetes management • Lipid-lowering agents (statins, Ezetimibe, PCSK9 inhibitor)
• Weight management • ACE inhibitor
- Patients w/ CHF, LV dysfunction (EF <40%), hypertension or DM
• Angiotensin II antagonist (for patients intolerant to ACE inhibitors)
• Aldosterone receptor antagonist (mineralocorticoid receptor
antagonist)
- For patients w/ reduced LV function
• Therapy for ischemic symptoms (as indicated)
- Beta-blocker - Calcium antagonist
- Nitrate - Trimetazidine
- Ranolazine - Ivabradine
- Nicorandil
Acute anginal episodes
• Short-acting sublingual nitrates
FOLLOW-UP
Low- & intermediate-risk medically
treated patients & revascularized patients
• Follow-up appointment in 2-6 weeks
High- & Very high-risk patients
• Follow-up appointment in 1-2 weeks
*Not recommended for patients w/ indications for PCI or CABG. UFH may be considered instead.
1 ISCHEMIC-TYPE CHEST DISCOMFORT OR ANGINAL EQUIVALENT

• Retrosternal chest pain
- Pain is usually described as heaviness, pressure, tightness, cramping or burning in nature
- Pain may occur at rest or during activity that may be associated w/ physical exertion or emotional stress
- The pain which is usually central or in the left chest may radiate to the jaw, neck, left or both arms, back or shoulder
• Accompanying symptoms may include: Nausea & vomiting (N/V), dyspnea, diaphoresis, lightheadedness,
abdominal (epigastric) pain, dizziness, fatigue, weakness & loss of consciousness
• Atypical pattern: Pain develops in the arm, shoulder, wrist, jaw or back without occurrence in the chest
- Discomfort that presents solely as jaw, neck, ear, arm or epigastric pain & is associated w/ exertion or stress
or is relieved promptly w/ Glyceryl trinitrate (GTN) should be considered equivalent to angina
• Pain is usually not relieved by rest or GTN
• Established risk factors (eg smoking, dyslipidemia, hypertension, diabetes & history of coronary artery disease)
- Please see page 6 for Risk Stratification
B3
2 DIAGNOSIS
Patients w/ suspected acute coronary syndrome must be evaluated quickly
Definitions
ACS
Acute Coronary Syndrome (ACS)

• Any constellation of symptoms compatible w/ acute myocardial ischemia usually caused by sudden reduction
in coronary blood flow
ACS encompasses the following:
• Unstable Angina (UA)
- Ischemic discomfort that presents without persistent ST-segment elevation on the ECG & without the
presence of cardiac markers in the blood
• Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)
- Diagnosed if cardiac markers are positive w/ ST-segment depression or w/ nonspecific or normal ECGs
• ST-Segment Elevation Myocardial Infarction (STEMI)
- Please see Myocardial Infarction w/ ST-Segment Elevation disease management chart for further information
Signs & Symptoms
• Patient typically presents w/ ischemic-type chest pain as described above, except that the episodes may be
more severe & prolonged, may occur at rest or may be caused by less exertion than previous episodes
• Atypical presentations are often observed in younger (25-40 years old) & older (>75 years old) patients, in
women, & in patients w/ DM, chronic renal failure or dementia
- Eg pain that occurs predominantly at rest, epigastric pain, recent onset of unexplainable indigestion, belching,
stabbing chest pain, chest pain w/ some pleuritic features or increasing dyspnea
• Common features of UA:
- Rest angina: Angina occurring at rest & prolonged, usually >20 minutes
- New-onset severe angina: Patient usually has marked limitation on ordinary physical activity (angina occurs
on walking 1-2 blocks on level or climbing 1 flight of stairs under normal conditions & at a normal pace)
- Increasing or crescendo angina: Previously diagnosed effort-related angina that has become distinctly more
frequent, longer in duration or more easily provoked (by less effort than before)
- Post-MI angina
Physical Exam
• Major objectives:
- Identify precipitating causes (eg uncontrolled hypertension, thyrotoxicosis or GI bleeding) & comorbid
conditions (eg lung disease or cancer)
- Assess the hemodynamic impact of the ischemic event
- Exclude noncardiac causes of chest pain (eg pneumothorax, pulmonary embolism, pneumonia, pleural
effusion, esophageal discomfort, gallstones, pancreatitis, or musculoskeletal origin)
- Assess for nonischemic cardiac disorders (eg pericarditis, valvular disease, aortic dissection, acute pericarditis,
cardiac tamponade)
• Measure vital signs (BP in both arms, HR, RR & temperature)
• Perform thorough CV & chest exam including auscultation of heart, neck veins, liver & peripheral pulses to
check for murmurs, bruits or pulse deficits which signify severe underlying coronary artery disease (CAD)
• LV dysfunction & shock should be suspected if patient has cold extremities, hypotension, pulmonary rales,
S3 gallop, displaced apex beat or S1<S2 at apex
• Aortic dissection may be present if there is pain in the back, unequal pulses, or a murmur of aortic regurgitation
• Acute pericarditis is suggested by a pericardial friction rub
• Cardiac tamponade may present as pulsus paradoxus
• If pneumothorax is present, patient may have acute dyspnea, pleuritic chest pain & differential breath sounds
• Chest pain caused by musculoskeletal chest wall syndromes may be found by performing palpation of the chest wall
ECG
In patients w/ ongoing chest pain, ECG should be obtained immediately (within 10 minutes of patient
entering hospital) & as soon as possible in patients w/ resolved symptoms at the time of evaluation
• ECG is key in the assessment of patients presenting w/ suspected ACS & an ECG taken during an episode of
chest pain is particularly valuable; ECG should be repeated (15- to 30-minute intervals at the 1st hour) as
necessary or if there is high suspicion for ACS
- Serial ECGs can identify ST-segment elevation indicative of STEMI which warrants immediate reperfusion
& detect evolving ischemic changes in initial non-diagnostic ECGs
• Comparison w/ a previous ECG, if available, is important, especially in patients w/ coexisting cardiac pathology
(eg LV hypertrophy or a previous MI)
• Continuous multilead ST-segment monitoring is an acceptable alternative to serial 12-lead ECG recordings
in patients w/ high clinical suspicion for ACS but w/ initial ECG that is nondiagnostic
B4
2 DIAGNOSIS (CONT’D)
ECG (Cont’d)
UA/NSTEMI
ACS
• ST-segment depression (especially horizontal or downsloping) >0.1 mV in ≥2 contiguous leads
- Highly suggestive of ACS
• Inverted T-waves >0.1 mV w/ predominant R-waves
- Less specific for ACS
• T-wave inversion: Marked >0.2 mV symmetrical T-wave inversion in the precordial lead
Other ECG Presentations
• Persistent ST-segment elevation or new or presumed new left bundle-branch block (LBBB) has a high specificity
for evolving STEMI
- Patient should then be immediately evaluated for reperfusion therapy
- Please see Myocardial Infarction w/ ST-Segment Elevation disease management chart for further
information
• A completely normal ECG does not exclude the possibility of ACS
- If normal ECG occurs during episode of chest pain, an alternative diagnosis should be suspected
Biochemical Indicators for Detecting Myocardial Necrosis
Cardiac Troponin T or I (Quantitative)
• High-sensitivity cardiac troponin I (hs-cTn I) assay is mandatory at presentation on patients w/ symptoms of
possible or suspected ACS & have normal or non-diagnostic findings on ECG
- Rule in MI if there is a significant rise &/or fall of cTn w/ at least 1 value >99th percentile URL together w/
other clinical criteria
- For values <99th percentile, algorithms for ruling out ACS include the HEART (history, ECG, age, risk factor,
troponin) pathway, European Society of Cardiology (ESC) 3-hour pathway & the ESC 1-hour pathway
- Cut-off levels for the different hs-cTn are assay specific; gender-specific cut-offs are also available
• cTn T & I are preferred markers for myocardial injury & necrosis because of high sensitivity & specificity
- Detected in blood at 6 hours using conventional assays (earlier w/ hs-cTn assays) & level may remain elevated
for up to 14 days
- Troponins accurately identify myocardial necrosis but should be used in conjunction w/ other criteria of MI
which include ischemic symptoms &/or ECG & imaging findings
Myoglobin &/or Creatine Kinase - Myocardial Band (CK-MB)
• May be measured in patients w/ recent (<6 hours) symptoms as an early marker of MI & in patients w/ recurrent
ischemia after recent (<2 weeks) infarction to detect further infarction
Other Biomarkers
• Myosin-binding protein C & copeptin are alternatives to cardiac troponin & CK-MB
Other Diagnostic Tests As Indicated
• CBC, creatinine, BUN, estimated glomerular filtration rate, C-reactive protein, blood glucose, B-type natriuretic
protein (BNP), N-terminal pro-BNP, lipid profile, thyroid function
- Detect the presence of anemia, thyrotoxicosis, DM, CAD
- Identify infection: Several studies have shown an associated increased risk for ACS within 1-2 weeks after
acute respiratory infection; absence of infection may be prognostic
• Chest X-ray to identify pulmonary congestion/edema & thoracic causes of symptoms
• Chest computed tomography (CT) to exclude pulmonary embolism & aortic dissection
- D-dimer determination should be considered instead of imaging studies to rule out pulmonary embolism
• Coronary CT angiography may be considered instead of invasive angiography in order to exclude CAD in
patients w/ normal or inconclusive troponin or ECG results
• Echocardiography may be used to assess LV function & eliminate other CV causes of chest pain
• MRI may be used to determine myocardial viability & exclude differential diagnoses (eg pulmonary embolism
or aortic dissection)
• Rest myocardial scintigraphy may be helpful in patients w/ chest pain without ECG changes or evidence of
ongoing MI
B5
3 REPEAT TESTS
ECG
• Perform serial ECGs or if patient experiences new episode of chest pain, obtain 12-lead ECG & compare w/
ACS
ECG taken without symptoms

• ECG recordings may be repeated at least 6-9 hours & 24 hours after presentation
- >24-hour rhythm monitoring is recommended in NSTEMI patients at increased risk for cardiac arrhythmia;
<24-hour monitoring is sufficient for those at low risk for cardiac arrhythmia
• For patients w/ highly suspicious ongoing ischemia, additional ECG leads (V3R, V4R, V7-V9) are
recommended
Biochemical Markers
• cTn test of <99th percentile should be repeated 3 hours later (2 hours later if hs-cTn)
- If >99th percentile or >50% change in levels within a 3-hour period*, patient is admitted
- If <99th percentile & <50% change in levels within a 3-hour period*, consider the following:
- Admit patient if still w/ pain &/or HEART score >3** or TIMI score ≥2**; exclude other diagnosis
- Discharge patient for early outpatient cardiology consult if without pain & HEART score <3** or TIMI
score is 0 or 1**
*If initial baseline cTn or hs-cTn is markedly >99th percentile, a change of >20% is significant; if baseline is less than or around the 99th
percentile, a change of at least 50% is required to be significant.
**Use HEART score for scoring if cTn is used. Use modified HEART score or Thrombolysis in Myocardial Infarction (TIMI) score if
hs-cTn is used.
4 FURTHER TESTING
• May be performed prior to discharge or as an outpatient to ascertain diagnosis
• Stress test to provoke ischemia
- Consider evaluation of LV function if ischemia is present
- If stress test is negative & history is still suggestive of ischemic pain, may consider nuclear scan, cardiac MRI
or diagnostic coronary angiogram
- If stress test is negative & history is not suggestive of ischemic pain, alternative diagnosis should be sought
• Treadmill ECG, stress myocardial perfusion imaging, or stress echocardiography before discharge or within
72 hours after discharge is suggested in patients w/ possible ACS who have normal serial ECGs & cardiac
troponins
• Treat patient appropriately
5 EVALUATION FOR RISK STRATIFICATION

Medical history, physical exam, ECG, biochemical cardiac markers & assessment of renal function can be
used to estimate the risk of death & nonfatal cardiac ischemic events
• Assessment of risk is useful in selection of site of care (eg ICU, monitored unit, outpatient) & in selection of
treatment
- Risk assessment should be done repeatedly
• Patients w/ high likelihood of ACS secondary to CAD are at greater risk of untoward cardiac events than
patients at less risk of CAD
- High likelihood signs & symptoms: Chest or left arm pain or discomfort as chief symptom reproducing prior
documented angina, known or prior history of CAD including MI, presence of transient mitral regurgitation,
murmur, hypotension, diaphoresis, pulmonary edema or rales, elevated cardiac markers, & ECG result of
new or presumably new, transient ST-segment deviation or T-wave inversion in multiple precordial leads
• Prognostic information to predict short- or mid-term risk of ischemic events, commonly use the Global
Registry of Acute Coronary Events (GRACE), the Thrombolysis in Myocardial Infarction (TIMI) risk score,
the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT)
risk score, & the National Cardiovascular Data Registry-Acute Coronary Treatment and Intervention Outcomes
Network (NCDR-ACTION) registry
B6
5 EVALUATION FOR RISK STRATIFICATION (CONT’D)

Very High-Risk Criteria
• Acute heart failure
ACS
• Arrhythmias (life-threatening) or cardiac arrest
• Hemodynamic instability or cardiogenic shock
• Mechanical complications of MI
• Recurrent dynamic ST-T wave changes w/ or without intermittent ST-elevation
• Recurrent or ongoing chest pain refractory to medical treatment
High-Risk Criteria
• Dynamic ST- or T-wave changes (symptomatic or silent)
• Rise or fall in cardiac troponin compatible w/ MI
• GRACE score >140
• TIMI risk score >4
Intermediate-Risk Criteria
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73m2)
• Left ventricular ejection fraction (LVEF) <40% or congestive heart failure
• Early post-infarction angina
• Previous revascularization (PCI/CABG)
• GRACE score >109 & <140
• TIMI risk score 3 & 4
Low-Risk Criteria
• Any characteristics not mentioned in above criteria
6 STRESS TEST
• Stress test may be performed in patients w/ low & intermediate risk who have no ischemia at rest or w/ low
level activity for a minimum of 12-24 hours; prior to discharge; or as an outpatient
• Confirms or establishes diagnosis of CAD & assesses risk for future CV events
• Patients w/ significant ischemia during exam should be considered for coronary angiography
7 INVASIVE STRATEGIES
• The timing of invasive strategy can be classified into the following:
- Immediate invasive strategy (<2 hours) in patients w/ at least one of the following: Acute heart failure w/
refractory angina or ST deviation, hemodynamic instability, life-threatening arrhythmias, MI mechanical
complications, ongoing or recurrent chest pain unresponsive to medical therapy, recurrent dynamic ST- or
T-wave changes
- Early invasive strategy (<24 hours) in patients w/ at least one of the following: Changes in cardiac troponin
level compatible w/ MI, dynamic ST- or T-wave changes, GRACE score of >140
- Invasive strategy (<72 hours) in patients w/ at least one of the following: DM, early post-infarction angina,
eGFR <60 mL/min/1.73 m2, LVEF <40%, previous CABG, recent PCI, GRACE score <140 & >109
Coronary Angiography
• Recommended in patients w/ intermediate- to high-risk features not responsive to intensive medical therapy
- Angiography is contraindicated when risks of revascularization do not outweigh the benefits (eg liver/
pulmonary/renal failure, cancer) & in patients (especially women) w/ acute chest pain & a low risk of ACS
who have negative troponin
• Recommended to be done immediately in patients w/ refractory or recurrent angina associated w/ dynamic
ST-deviation, heart failure, life-threatening arrhythmias or hemodynamic instability despite intensive medical
therapy
• A radial approach is preferred for both coronary angiography & PCI
B7
7 INVASIVE STRATEGIES (CONT'D)

Revascularization
• Relieve angina or ongoing MI & prevent progression of MI to death
ACS
• PCI vs CABG: Choice of revascularization procedure will depend on extent & severity of lesion based on
coronary angiography, condition of patient, & coexisting illness, particularly in patients w/ multivessel CAD
• Appropriate use criteria for revascularization recommended by the American College of Cardiology (ACC),
American Association for Thoracic Surgery (AATS), American Heart Association (AHA), American Society
of Echocardiography (ASE), American Society of Nuclear Cardiology (ASNC), Society for Cardiovascular
Angiography and Interventions (SCAI), Society of Cardiovascular Computed Tomography (SCCT), & the
Society of Thoracic Surgeons (STS):
- Patients w/ evidence of cardiogenic shock w/ ≥1 coronary arteries for immediate revascularization
- Risk versus benefit ratio should be considered in this group of patients
- Stable patients at immediate-/high-risk for clinical event & w/ ≥1 coronary arteries for revascularization
- May be considered in stable patients w/ low risk for clinical events & w/ ≥1 coronary arteries for
revascularization
• PCI is found to be beneficial in patients w/ 1- to 2-vessel CAD, w/ or without significant proximal left anterior
descending CAD, but w/ a large area of viable myocardium & high-risk criteria on non-invasive testing
- A drug-eluting stent may be offered to those undergoing revascularization by PCI
• CABG is recommended in patients w/ disease of the left main coronary artery, involvement of multiple vessels,
& other high-risk patients such as those w/ ventricular dysfunction or diabetes
A PHARMACOLOGICAL THERAPY
Antiplatelet Agents1
• In patients w/ ACS treated only w/ medical therapy, PCI or CABG, 12 months of dual antiplatelet therapy
(DAPT) (Aspirin plus a P2Y12 receptor inhibitor) is recommended
- Consider continuing therapy >12 months in patients w/ previous MI & tolerant of DAPT w/ no bleeding complication
- Consider at least 1 month of DAPT in patients treated only w/ medical therapy & at high risk of bleeding
- Consider stopping therapy after 6 months in patients treated w/ PCI or CABG & at high risk of bleeding
• For long-term treatment, adding a 2nd antithrombotic agent to Aspirin should be considered in patients at
high risk of ischemic events without high risk for bleeding & may be considered in patients w/ moderate risk
Aspirin
• Should be given promptly & continued daily in all patients w/ suspected ACS, unless there are contraindications
- Initial loading dose of 160-325 mg (non-enteric formulation & should be chewed), followed by 75-100 mg
(soluble/enteric coated formulation) daily to be continued indefinitely
- 75-100 mg of Aspirin is recommended in patients being treated w/ DAPT
• Exerts antithrombotic effect by irreversible inhibition of cyclooxygenase-1 within platelets which prevents
production of platelet-aggregating substance, thromboxane A2
• Administration of daily Aspirin has been shown to consistently decrease risk of death & MI in patients w/ UA
• May be withheld 7-10 days prior to elective CABG
Cangrelor
• Recommended for patients who may be considered for P2Y12-inhibitor-naive patients undergoing PCI
• An IV adenosine triphosphate analogue that binds reversibly & w/ high affinity to the platelet P2Y12 receptor
& has a short plasma half-life
• Produces a highly effective inhibition of ADP-induced platelet aggregation immediately after IV bolus
administration & allows for restoration of platelet function within 1-2 hours of infusion discontinuation in
NSTE-ACS patients
Clopidogrel
• Recommended in combination w/ Aspirin in UA/NSTEMI patients wherein Ticagrelor or Prasugrel is
unavailable or contraindicated
- Initial dose of 300 mg, followed by 75 mg daily for at least 1 month & ideally up to 12 months
- In patients w/ definite NSTEMI undergoing an invasive management, an initial dose of 600 mg followed by
75 mg daily may be considered
• Prodrug that actively biotransforms into molecules that bind irreversibly to the P2Y12 receptor which reduces
platelet adhesion & aggregation
• When combined w/ Aspirin, Clopidogrel has been shown to reduce CV death, MI & stroke in patients w/
UA/NSTEMI
• Has a better safety profile as compared to Ticlopidine but w/ the same consistency & degree of P2Y12 inhibition
& risk of bleeding
• In ACS patients on long-term Clopidogrel, switching to Ticagrelor from Clopidogrel may be considered early
following hospital admission regardless of the loading dose & timing of Clopidogrel therapy
• If possible, discontinue at least 5 days before elective CABG
1P2Y receptor inhibitors (Cangrelor, Clopidogrel, Prasugrel, Ticagrelor) are listed in alphabetical order.
12
B8
A PHARMACOLOGICAL THERAPY (CONT’D)

Antiplatelet Agents1
(Cont’d)
Prasugrel
ACS
• Recommended in combination w/ Aspirin in P2Y12 inhibitor-naive patients in whom coronary anatomy is
known & who will undergo PCI
- Initial dose of 60 mg to be given at the time of PCI, followed by 10 mg daily for 12 months
• Should be considered the preferred P2Y12 inhibitor in NSTEMI patients who will undergo PCI
- In the Intracoronary stenting & Antithrombotic regimen Rapid Early Action for Coronary Treatment
(ISAR-REACT) 5 trial, Prasugrel showed significantly lower incidence in mortality, MI or stroke without
any increase in bleeding, & less treatment discontinuation due to side effects in patients w/ planned invasive
evaluation when compared to Ticagrelor
• Thienopyridine prodrug that requires conversion to its active metabolite that inhibit platelet activation &
aggregation
• Studies have shown that it is superior to Clopidogrel in reducing ischemic events including stent thrombosis
- Has faster & consistent onset of action & degree of P2Y12 inhibition as compared to Clopidogrel
- Studies have shown that it has increased risk for major bleeding, including fatal bleeding
• Not recommended in patients w/ prior history of stroke or TIA; administer w/ caution in patients >75 years
old & weigh <60 kg
• May be withheld for at least 7 days prior to elective CABG
Ticagrelor
• Recommended in combination w/ Aspirin in UA/NSTEMI/STEMI patients w/ intermediate to high risk of
ischemic events regardless of initial choice of therapy (invasive or conservative, including pre-treatment w/
Clopidogrel)
- Initial dose of 180 mg, then 90 mg 12 hourly for 12 months
- Ticagrelor 60 mg 12 hourly for >12 months in combination w/ Aspirin may be preferred over Clopidogrel or Prasugrel
in patients w/ MI & high risk of ischemia & tolerant of DAPT w/ no bleeding complication
- Studies show that Aspirin ≥300 mg/day decreases the efficacy of Ticagrelor; Aspirin 75-100 mg is recommended
in patients being treated w/ DAPT
• A member of the chemical class cyclopentyltriazolopyrimidines (CPTP), Ticagrelor is a reversible, direct-acting
oral antagonist of the P2Y12 receptor that does not require transformation to an active metabolite
• Superior to Clopidogrel in reducing clinical events
- Studies have shown that it has lower rates of MI, definite stent thrombosis, vascular death & all-cause mortality
- Has faster & consistent onset & offset of action as compared to Clopidogrel
- Studies have shown that it has an increased risk of non-procedure-related bleeding but without an increased
rate of overall major bleeding
• Preferred over Clopidogrel for maintenance P2Y12 inhibitor therapy in the following subset of patients w/
ACS:
- Patients on medical therapy alone, ie without fibrinolytic therapy or revascularization, treated w/ DAPT
- Patients treated w/ DAPT following implantation of a coronary stent
• May be withheld for at least 3 days prior to elective CABG
Glycoprotein IIb/IIIa Inhibitors
• Mainly used in patients w/ a large thrombus discovered during coronary angiography
• During PCI, it should be considered in bailout situations or thrombotic situations in patients previously treated
w/ Prasugrel or Ticagrelor
• Acts by occupying the GP IIb/IIIa receptors, preventing fibrinogen binding, thus reducing platelet aggregation
• Several trials showed a consistent reduction of thrombotic complications, especially peri-procedural MI in
patients undergoing PCI
• Abciximab
- Start & continue for 12 hours after PCI
- Indicated only in patients in whom PCI is planned
- Has a longer half-life than other GP IIb/IIIa inhibitors & excessive bleeding can occur in cardiac surgery
patients
• Tirofiban or Eptifibatide
- Start & continue for 24 hours after PCI
- May be used in patients w/ high-risk UA/NSTEMI in conjunction w/ standard therapy if PCI is not planned
& if bleeding risk is low
- Binds reversibly to GP IIb/IIIa receptor
1P2Y receptor inhibitors (Cangrelor, Clopidogrel, Prasugrel, Ticagrelor) are listed in alphabetical order.
12
B9

Antiplatelet Agents (Cont’d)
Vorapaxar
ACS
• A protease activated receptor-1 (PAR-1) antagonist that inhibits platelet activation

• Studies showed that Vorapaxar, when given w/ other antiplatelet agents, significantly reduced incidences of
MI, stroke, & death caused by cardiovascular disease
If CABG is to be performed, discontinue GP IIb/IIIa antagonist at the time of or 4 hours prior to procedure
Anticoagulants
• Anticoagulation is recommended for all UA/NSTEMI patients using any of the following: Unfractionated
Heparin, LMWH, Bivalirudin or Fondaparinux
• Prevents thrombus formation at the site of arterial injury, on the coronary guide wire, & in the catheters used
for PCI
• In patients who require oral anticoagulants, consider 1 month of triple therapy w/ Aspirin, Clopidogrel & an
oral anticoagulant in patients who have undergone coronary stent implantation
• In non-ST elevation-ACS patients w/ atrial fibrillation who underwent PCI, risk of bleeding is lower w/ the
use of direct oral anticoagulants & antiplatelet therapy than w/ standard triple therapy
Low-Molecular-Weight Heparin (LMWH)
• Recommended over UFH for UA/NSTEMI patients in whom early conservative or delayed invasive management
is contemplated
• Acute treatment w/ SC LMWH is considered at least as effective as IV UFH
• Enoxaparin twice daily has shown better outcomes (reduced death, MI or recurrent angina) when compared
to UFH & is considered preferable in UA/NSTEMI patients in the absence of renal failure unless CABG is
planned within 24 hours
- Calculating creatinine clearance is essential in Enoxaparin therapy
• Similar to Heparin, these compounds enhance the action of antithrombin III but they have a higher ratio of
anti-factor Xa to antithrombin activity than Heparin
• Advantages of LMWH over UFH
- Monitoring of anticoagulant aPTT is not required
- Ease of subcutaneous administration w/ LMWH
- Lower risk of Heparin-induced thrombocytopenia (HIT) than UFH but similar risk for bleeding
• LMWH should be discontinued if CABG is planned, use UFH instead during the operation
• Studies have shown significant reduction in total ischemic event rate, recurrent angina rate, need for
revascularization, MI or death during treatment period using combination of Aspirin & LMWH
Unfractionated Heparin (UFH)
• Dosing should be based on weight
• Activated partial thromboplastin time (aPTT) should be maintained at 50-70 seconds or 1.5-2x normal
• Enhances antithrombin III activity causing decrease in activity of clotting factors including thrombin & factor
Xa; UFH also has antiplatelet function
Factor Xa Inhibitors
• In patients w/ non-ST elevation-ACS & atrial fibrillation undergoing PCI or medical management, direct oral
anticoagulants (eg Apixaban, Dabigatran, Rivaroxaban) are preferred over VKA if without contraindications
Apixaban
• May be considered in patients w/ atrial fibrillation together w/ Clopidogrel for at least 6 months
- Combination therapy has less bleeding & fewer hospitalizations w/ no significant differences in the incidence
of ischemic events when compared to regimens that included Aspirin, Warfarin, or both
Fondaparinux
• A parenteral selective factor Xa inhibitor which is a synthetic polysaccharide molecule
• Recommended over Enoxaparin (LMWH) for UA/NSTEMI patients in whom early conservative or delayed
invasive management is to be used
• Acts by selective antithrombin-mediated inhibition of factor Xa
• Can be given once daily because of 100% bioavailability & elimination half-life of 17 hours
• No incidence of HIT has been reported
• Should not be given if patient is likely to undergo CABG within 24 hours or if CrCl is <30 mL; use UFH instead
• A large study comparing Fondaparinux w/ Enoxaparin in UA/NSTEMI patients showed less major bleeding
w/ the use of Fondaparinux but similar reduction in the risk of ischemic events in both groups
Rivaroxaban
• Consider low-dose Rivaroxaban for approximately 1 year after stopping parenteral anticoagulation in NSTEMI
patients without prior TIA or stroke history, & at high risk of ischemia & low risk of bleeding on Aspirin &
Clopidogrel
• For patients w/ recurrent ischemia, low-dose Rivaroxaban for >1 year may also be considered
B10

Direct Thrombin Inhibitors
Argatroban
ACS
• For prophylaxis or treatment of thrombosis in patients w/ HIT, including those undergoing PCI
• Can be used in patients w/ renal insufficiency
Bivalirudin
• Recommended as an alternative anticoagulant for urgent & elective PCI
• It can also be used for treating HIT complicated by thrombotic events
• Binds directly to thrombin (factor IIa), inhibiting the thrombin-induced conversion of fibrinogen to fibrin
• Bivalirudin compared w/ UFH, in the setting of PCI, decreased the rate of major adverse cardiac events (eg
death, MI or repeat revascularization) & rate of bleeding
• Bivalirudin is comparable to UFH in protecting patients against ischemia during PCI & also showed lower
bleeding complications
Antianginal Agents
• Antianginal agents required in the hospital, should be continued in patients who did not undergo coronary
revascularization, in patients who had unsuccessful revascularization & in patients w/ recurrent symptoms
after revascularization
- Adjustment of doses may be required
Acute Anginal Episodes
• All patients should be given short-acting sublingual nitrates & instructed on the proper use
Beta-Blockers
• Recommended to be given within the first 24 hours in ACS patients w/ ongoing ischemic symptoms in the
absence of contraindications (eg signs of HF, evidence of low-output state, increased risk for cardiogenic shock)
& should be started early in treatment especially in patients who will undergo cardiac or noncardiac surgery
• May be used to manage BP, angina & rhythm if needed
• Acts by inhibition of catecholamine action that results in reduction of myocardial contractility, sinus node
rate & AV node conduction
- This causes a blunted effect on HR & contractility responses to chest pain, exertion & other stimuli
• Decreases myocardial O2 demand (by blocking the beta1-adrenergic receptor)
- Reduction in HR also increases diastolic perfusion time, which may enhance LV perfusion
- Studies of beta-blockers in UA have been small but larger randomized trials w/ other CAD patients (AMI, recent
MI, stable angina w/ daily life ischemia & heart failure) have shown reductions in mortality &/or morbidity rates
- Improve prognosis in patients after MI thus should be continued after ACS
• Oral therapy should be dosed to HR of 50-60 bpm
• May lead to significant increase in survival
Nitrates
• Sublingual nitrate followed by IV therapy should be used for the immediate relief of ischemia & associated
symptoms
- IV nitrate is recommended in patients whose symptoms are not relieved w/ 3 doses of sublingual nitrate,
dynamic ECG changes are present, have left ventricular failure or have concomitant hypertension
- Once patient has been pain-free for 12-24 hours of IV nitrate, attempt should be made to reduce IV dose
& replace w/ topical/oral therapy
• Topical or oral nitrates are acceptable alternatives for those without ongoing refractory ischemic symptoms
- Oral/topical nitrates may be given after 12-24 hours of pain-free period after IV administration
• Use is contraindicated in patients w/ recent intake of phosphodiesterase inhibitors (ie Sildenafil, Vardenafil)
• Induce relaxation of the vascular smooth muscle in veins, arteries & arterioles which results in vasodilation
- This reduces RV & LV preload along w/ afterload reduction which decreases cardiac work & myocardial O2
demand
Calcium Antagonists
• May be used to control ongoing or recurring ischemia-related symptoms in patients who are already given
adequate doses of nitrates & beta-blockers
- May be considered in patients who are unable to tolerate adequate doses of one or both of these agents, in
those w/ contraindications to beta-blockade, or in those w/ variant angina
- Avoid Ca antagonists in those w/ significantly impaired LV function or AV conduction especially Verapamil
• Ca antagonists exert negative inotropic effects, reduce smooth muscle tension in the peripheral vascular
system which is associated w/ vasodilation
- Decrease coronary vascular resistance & increase coronary blood flow
- Cause dilation of the epicardial conduit vessels & the arteriolar resistance vessels
B11

Antianginal Agents (Cont'd)
Calcium Antagonists (Cont'd)
ACS
• Clinical trials have shown Ca antagonists (eg Diltiazem, Verapamil) to be as effective as beta-blockers in
relieving angina & improving exercise tolerance
- Meta-analysis of Ca antagonists in UA has shown that this class of drug does not prevent the development
of acute MI or reduce mortality
• Verapamil & Diltiazem are the preferred Ca antagonists
- Nifedipine or other Dihydropyridines should not be used without concomitant beta-blocker therapy
(especially short-acting agents)
- The choice of an individual Ca antagonist is based primarily on the type of agent, hemodynamic state of the
patient, risk of side effects on cardiac contractility, AV conduction & sinus node function & physician’s
familiarity w/ the specific agent
Opioids
• Eg IV Morphine or Diamorphine
• Recommended for patients whose symptoms are not relieved after 3 doses of sublingual nitrate or whose
symptoms recur despite adequate anti-ischemic therapy
- May be administered along w/ IV nitrate, w/ careful BP monitoring, & in the absence of hypotension or
intolerance
• Potent analgesic & anxiolytic opioids also cause venodilation & may produce modest reductions in HR &
systolic BP, thus reducing myocardial O2 demand
High-intensity Statins
• Assess fasting lipid profile in all patients & within 24 hours of hospitalization for those patients who present
w/ an acute event
• High-intensity statin therapy should be started upon admission in all NSTE-ACS patients & maintained long
term if there are no contraindications
- Long-term lipid management includes addition of Ezetimibe to a maximally tolerated statin dose after
4-6 weeks if LDL-C is not at goal; if despite this LDL-C is still not at goal, then PCSK9 inhibitors may be
considered
ACE Inhibitors1
• Recommended in patients w/ chronic heart failure (CHF), LV dysfunction (EF <40%), hypertension, DM or
stable chronic kidney disease
• Exhibit cardioprotective effects by promoting vasodilatory, antiproliferative, antiaggregatory & antithrombotic
effects
• Studies have shown reduction in cardiac events in patients w/ LV dysfunction w/ known CAD
- Meta-analysis of 3 major trials supported benefit in using ACE inhibitors across the risk spectrum studied;
these provide general benefit in stable CAD, but the benefit is proportional to disease-related risk, w/ low-risk
patients having the least benefit
Angiotensin II Antagonists1
• May be used in patients w/ MI or heart failure & reduced LV systolic function (EF <40%) who cannot take
ACE inhibitors
Aldosterone Antagonists (Mineralocorticoid Receptor Antagonists)1
• Eg Spironolactone, Eplerenone
• Considered in patients after MI who have been treated w/ ACE inhibitors & beta-blockers & have decreased LV
systolic function (EF <40%) & either w/ DM or heart failure
• Contraindicated in severe renal failure & hyperkalemia
Other Agents
Ivabradine
• Approved for chronic stable angina & stable chronic heart failure but is currently being considered for patients
w/ UA w/ contraindications to beta-blockers
• Selectively inhibits cardiac pacemaker current If which controls spontaneous diastolic depolarization in the
sinoatrial node
• Has been associated w/ decreased risk for revascularization
Nicorandil
• May be used as an alternative to nitrates in stable angina patients but there is less data available for use in ACS
• Activates the potassium ATP channel & increases coronary blood flow by dilation of coronary arteries &
reduces myocardial O2 demand by reduction in afterload & to a lesser extent, preload
• The addition of this drug to conventional therapy significantly reduced the number of episodes of transient
MI (mostly silent) & of ventricular & supraventricular tachycardia in a small pilot study
- Another study showed decrease in occurrence rate of coronary death, non-fatal MI, or unplanned hospital
admission due to cardiac pain in chronic stable angina, but not in the setting of NSTEMI
1Pleasesee Hypertension & Heart Failure - Chronic disease management charts for dosing recommendations of ACE inhibitors,
Angiotensin II antagonists & Aldosterone antagonists.
B12

Other Agents (Cont'd)
Ranolazine
ACS
• Can be used alone or in combination w/ Amlodipine, beta-blockers or nitrates for the treatment of chronic
angina that is not responsive to standard antianginal treatment
• Contraindicated in patients w/ QT-prolonging conditions
• Exerts antianginal effects by inhibiting the late sodium current without reducing HR or BP & reduces the
adverse effects of intracellular sodium & calcium overload that accompany myocardial ischemia
• Results of a large study suggested safety & symptom relief but no significant reduction in CV death, MI or
recurrent ischemia
Trimetazidine
• Exerts metabolic effects without hemodynamic changes
• In small trials, use has been shown to improve LV function & has been associated w/ decreased mortality
Proton Pump Inhibitors
• Given to patients at high risk of GI bleeding who are receiving Aspirin monotherapy, DAPT, dual or triple
antithrombotic therapy or oral anticoagulation monotherapy
B SUPPORTIVE THERAPY
Bed Rest
• Usually prescribed initially in patients w/ UA/NSTEMI while ischemia is ongoing
- Patient can be mobilized to bedside commode or chair when symptom-free
• Ambulation as tolerated may begin once patient has been hemodynamically stable without recurrent symptoms
for 12-24 hours
- Subsequent activity should not be inappropriately restricted
- Focus should be on the prevention of recurrent symptoms & activity may be increased once patient responds
to therapy
Supplemental O2
• Give supplemental O2 to all patients w/ overt pulmonary congestion or arterial O2 saturation <90% or respiratory
distress or other high-risk features of hypoxemia
• Consider in all patients w/ ACS for the 1st 6 hours of therapy
C PATIENT & CAREGIVER EDUCATION

• Patient counseling tends to improve patient compliance & outcomes
• Assess the functional capacity & the ability to carry out daily activities or work of the patient
• Educate the patient & caregivers about UA & CVD
- Discuss the nature of the disease, drug regimens, lifestyle modifications & symptoms of angina
• Before hospital discharge, provide instructions w/ respect to medication type, purpose, dose, frequency &
side effects
• Patient & caregivers should be instructed on what steps to take if anginal symptoms occur
- Patient should be instructed to take sublingual nitrate & to seek emergency medical attention if 3 doses of
nitrate fail to relieve pain
- Explain to patient that if anginal symptoms change (eg pain more frequent, or occurs at rest, etc), they
should contact their physician
• Education should be a part of every patient encounter & should be tailored to the patient’s level of
understanding
- May be best to develop a plan w/ the patient & hold discussions over time so that patient is not overwhelmed
by changing several behaviors all at one time (eg smoking, diet, exercise, etc)
• Enlisting family members into the educational process to assist in achieving risk-factor modifications may be helpful
- Eg cooking low-fat meals for the entire family or family exercise to further support the patient in changing
risk behavior
- Particularly important when screening of family members reveals common risk factors (eg hyperlipidemia,
hypertension & obesity)
• Inform schedule for follow-up after discharge
- Low-risk medically treated patients & revascularized patients should return in 2-6 weeks
- Higher risk patients should return within 2 weeks
B13
C PATIENT & CAREGIVER EDUCATION (CONT'D)

• Annual influenza vaccination is recommended
• Patient’s need for treatment of chronic musculoskeletal pain or discomfort should be assessed; pain relief
should begin w/ Paracetamol, small doses of narcotics or nonacetylated salicylates
ACS
• Antioxidant vitamins (eg vitamin E, C or beta-carotene) & folic acid w/ or without vitamins B6 & B12, should
not be used for secondary prevention in UA/NSTEMI patients
Activity
• Daily walking may be encouraged immediately after discharge
• Exercise training can be started within 1-2 weeks after PCI or CABG to relieve ischemia
• Discuss safety & timing of resumption of sexual activity
- Usually 1-2 weeks for low-risk patients & 4 weeks for post-CABG
• Give advice on resumption of driving (usually 1 week) if stressful driving conditions are avoided
• Recommend timing of returning to work
• Air travel may resume within 2 weeks of discharge, if patient travels w/ companion, carries sublingual GTN
& takes airport transport to avoid rushing
D RISK FACTOR MANAGEMENT

• It is important to assess the presence of coronary heart disease (CHD) risk factors & to treat these effectively
- There is evidence that the treatment of risk factors reduces the risk of coronary disease events
- The presence of these risk factors appear to relate to poor outcomes in patients w/ established ACS
Smoking Cessation
• There are observational studies that show cigarette smoking increases the risk for CV disease events, insulin
resistance & DM
- Dose-dependent relationship exists between cigarettes smoked & CV risks
• Primary goal is complete smoking cessation
• Assess patient’s tobacco use & strongly urge patient & family to stop smoking
• Identify which patients are willing to quit
- Quit plan should be developed & pharmacological therapy (eg nicotine replacement, Bupropion, Varenicline),
counseling & formal cessation programs should be provided, if needed
• Aside from smoking cessation, avoidance of exposure to environmental smoke is also recommended
BP Control
• Primary goal1: BP <130/80 mmHg
• BP should be monitored in all CHD patients
- Start & maintain lifestyle modification (weight control, physical activity, diet modification, etc) in all patients
w/ SBP ≥130 or DBP ≥80 mmHg
- Start BP drug therapy which is tailored to patient’s requirements & characteristics (eg race, age, need for
drugs w/ specific benefits) if above primary goals are exceeded
• Please see Hypertension disease management chart for further information
Lipid Management
• Lifestyle modification should be advised (diet <7% saturated fat intake & <200 mg/day cholesterol, physical
activity & weight management)
• Lipid-lowering therapy decreases vascular events & death after MI or UA in patients w/ average-high cholesterol
• Statins should be given to patients before discharge from hospital, regardless of baseline LDL-C & diet
modification
• Cholesterol-lowering therapy should be started or intensified in UA/NSTEMI patients
- May be initiated early (24-96 hours after hospital admission & continued after hospital discharge to provide
life-long benefits)
- Studies have shown that giving statins in acute treatment of UA/NSTEMI reduces major adverse cardiac
events due to its pleotropic effects
- Treatment goal is LDL-C level of <1.4 mmol/L (<55 mg/dL) & a reduction of at least 50% if baseline LDL-C
level is >1.8 mmol/L (>70 mg/dL)
- Consider adding Ezetimibe to further lower LDL-C in patients w/ LDL-C ≥1.8 mmol/L despite statin
therapy at maximally tolerated dose, & a PCSK9 inhibitor may be considered if LDL-C is not at goal w/
Ezetimibe & a maximally tolerated statin
• Nicotinic acid (Niacin) & fibric acid derivatives (Fenofibrate, Gemfibrozil) may be therapeutic options (after
LDL-C lowering therapy) for patients w/ HDL-C <40 mg/dL & triglycerides >200 mg/dL to reduce residual
risk in patients who have achieved LDL-C target goals
• Please see Dyslipidemia disease management chart for further information
1Recommendations for BP treatment goals may vary between countries. Please refer to available guidelines from local health authorities.
B14
D RISK FACTOR MANAGEMENT (CONT’D)

Diabetes Management
• Initiate appropriate pharmacological therapy & lifestyle modification to achieve near-normal fasting plasma
ACS
glucose [<6.1 mmol/L (110-180 mg/dL)] or near-normal HbA1c (<6.5-7%)
• Less stringent glucose control may be more appropriate in patients w/ more advanced CVD, older age, longer
diabetes duration, & significant comorbidities
• Please see Diabetes Mellitus disease management chart for further information
Weight Management
• Calculate BMI & measure waist circumference as part of patient assessment every visit
• Goal BMI for Asian adults: 18.5-22.9 kg/m2, BMI for American/European adults: 18.5-24.9 kg/m2
• Recommended waist circumference (measure horizontally at the iliac crest)
- Asian men: <35 in (90 cm); American/European men: <40 in (102 cm)
- Asian women: <31.5 in (80 cm); American/European women: <35 in (88 cm)
• Initial goal of weight loss therapy should decrease the body weight by 10% from baseline; further weight
reduction can be attempted if indicated after further assessment
• Risk of coronary disease & mortality is increased in obese patients
- Obesity also contributes to other CHD risk factors (eg hypertension, low HDL-C, glucose intolerance, etc)
- The presence of abdominal obesity particularly raises CV risk
• Encourage physical activity, caloric restrictions & behavioral programs to have the ideal body mass index
Increase in Physical Activity
• Minimum goal: 30-60 minutes per day of moderate aerobic physical activity preferably everyday but at least
5 days/week, if tolerable
• Assess risk preferably w/ exercise test prior to prescribing exercise program
- Cardiac rehabilitation & secondary prevention programs w/ supervised exercise training are recommended
for patients w/ multiple risk factors & those moderate- to high-risk patients
- Cardiac rehabilitation programs can contribute in decreasing mortality & improving physical & emotional
well-being of patients after MI
Diet Modification
• Diet low in saturated fat, low in salt, high in polyunsaturated fat & high in fresh fruits & vegetables may assist
in preventing recurrent CV events
• If attempting to lower cholesterol w/ diet modification, please see Dyslipidemia disease management chart
for more specific recommendations
B15
Dosage Guidelines
ACS
ANTIPLATELET AGENTS
Drug Dosage Remarks
Aspirin1 Loading dose: Chew Adverse Reactions
160-325 mg • GI effects (GI upset which may be minimized by
non-enteric-coated x 1 dose administering w/ food & w/ use of enteric-coated
followed by: formulation, also GI irritation including erosion,
Aspirin alone: 75-100 mg ulceration, etc); Hematologic effects (increased bleeding
PO 24 hrly time, decreased platelet adhesiveness, hemorrhage);
Maintenance dose if Hypersensitivity reactions
combined w/ Clopidogrel/ Special Instructions
Ticagrelor: 75-100 mg PO • Contraindicated in patients w/ active pathological
24 hrly bleeding (eg peptic ulcer, intracranial hemorrhage),
known allergy, hemophilia, hemorrhagic disorders,
severe renal or hepatic impairment
• Ensure that benefit outweighs the risk prior to use in
combination w/ Warfarin, Heparin, thrombolytics,
NSAIDs & other drugs that increase the risk of bleeding
Cangrelor 30 mcg/kg IV bolus prior to Adverse Reactions
PCI followed by 4 mcg/kg/ • Hematologic effect (hemorrhage/bleeding); Other effects
min continuous IV infusion (renal impairment, dyspnea, hypersensitivity reaction)
over at least 2 hr or for the Special Instructions
duration of the PCI,
whichever is longer • Contraindicated in patients w/ active pathological
bleeding
• An oral P2Y12 platelet inhibitor must be administered
after Cangrelor infusion to maintain platelet inhibition
Clopidogrel Loading dose: 300 mg PO Adverse Reactions
followed by 75 mg PO 24 hrly • Hematologic effects (hemorrhage, purpura, epistaxis;
PCI for ACS patients: blood dyscrasias, including neutropenia, thrombotic
300-600 mg PO loading dose thrombocytopenic purpura have occurred);
prior to or at the time of PCI, Dermatologic effects (rash, pruritus); GI effects
followed by 75 mg PO 24 hrly (abdominal pain, N/V, dyspepsia, constipation)
(in combination w/ Aspirin) Special Instructions
• Contraindicated in patients w/ active bleeding or severe
liver impairment
• Concurrent use of drugs known to inhibit CYP2C19
(eg Omeprazole, Esomeprazole, Cimetidine, Fluconazole,
Ketoconazole, Voriconazole, Etravirine, Felbamate,
Fluoxetine, Fluvoxamine & Ticlopidine) should be
avoided
- Separating the time of administration between the
drugs does not reduce the chance of interaction
• If possible, discontinue use 7-10 days prior to elective
surgery
1Combinations of Aspirin/Glycine & Aspirin/Clopidogrel are available.
All dosage recommendations are for non-pregnant & non-breastfeeding women,

& non-elderly adults w/ normal renal & hepatic function unless otherwise stated.
B16
Dosage Guidelines
ACS
ANTIPLATELET AGENTS (CONT’D)
Drug Dosage Remarks
Prasugrel Co-administered w/ Aspirin: Adverse Reactions
Loading dose: • GI effects (N/V, diarrhea); Dermatologic effect (rash);
60 mg PO followed by Hepatic effects (elevated LFT, rarely hepatitis &
Maintenance dose: cholestatic jaundice); Hematologic effects (neutropenia,
<60 kg: 5 mg PO 24 hrly x thrombotic thrombocytopenic purpura, agranulocytosis,
12 mth hemorrhage)
≥60 kg: 10 mg PO 24 hrly x Special Instructions
12 mth • Contraindicated in patients w/ active bleeding,
hemorrhagic diatheses, patients w/ history of leukopenia,
thrombocytopenia or agranulocytosis
• Use w/ caution in patients w/ hepatic impairment
• Use w/ caution when combining w/ Warfarin, Heparin,
thrombolytics, NSAIDs & other drugs that increase the
risk of bleeding
• Consider discontinuation 7 days prior to surgery
• Contraindicated in patients w/ history of stroke or TIA,
in severe hepatic impairment
• In patients w/ <60 kg body wt, reduce maintenance dose
to 5 mg PO 24 hrly
Ticagrelor Co-administered w/ Aspirin: Adverse Reactions
Single loading dose: 180 mg • Hematologic effect (bleeding); Resp effect (dyspnea); CNS
PO followed by effects (headache, dizziness); ENT effects (epistaxis,
Maintenance dose: 90 mg PO vertigo); GI effects (abdominal pain, N/V, constipation,
12 hrly x 12 mth diarrhea); Metabolic effect (hyperuricemia); Dermatologic
When an extended treatment effects (rash, pruritus); Other effect (post-procedural
is required for patients w/ a hemorrhage)
history of MI of at least 1 yr & Special Instructions
a high risk of an • Contraindicated in patients w/ active pathological
atherothrombotic event: bleeding, intracranial hemorrhage history, known allergy,
60 mg PO 12 hrly or severe hepatic impairment
• Use w/ caution in patients w/ increased risk for
bradycardia
• Avoid abrupt discontinuation of therapy or therapy lapses

B17
Dosage Guidelines
ACS

Drug Dosage Remarks
Ticlopidine 250 mg PO 12 hrly Adverse Reactions
• GI effects (N/V, diarrhea); Dermatologic effect (rash);
Hepatic effects (elevated LFT, rarely hepatitis &
cholestatic jaundice); Hematologic effects (neutropenia,
thrombotic thrombocytopenic purpura, agranulocytosis,
hemorrhage)
Special Instructions
• Contraindicated in patients w/ active bleeding,
hemorrhagic diatheses, patients w/ history of leukopenia,
thrombocytopenia or agranulocytosis
• Use w/ caution in patients w/ hepatic impairment & when
combining w/ Warfarin, Heparin, thrombolytics, NSAIDs
& other drugs that increase the risk of bleeding
• Consider discontinuation 10 days prior to surgery prior
to surgery
• CBC w/ differential & platelet counts should be taken at
the start of treatment then every 2 wk for the 1st 3 mth of
therapy & within 15 days of discontinuation (if
discontinued within the 1st 3 mth of treatment)
Triflusal 600 mg/day PO in single or Adverse Reactions
divided dose or 900 mg/day • GI effects (dyspepsia, N/V, abdominal pain, constipation,
PO in divided doses flatulence); Other effects (anorexia, headache)
• Contraindicated in patients w/ hypersensitivity to other
salicylates, active, antecedent or complicated peptic ulcer
or other active pathological bleeding
• Use w/ caution in patients w/ renal or hepatic
impairment, increased risk of bleeding from trauma or
other pathological conditions; ASA- or other
NSAIDs-induced lesions
• Discontinue use 7 days prior to surgery

B18
Dosage Guidelines
ACS
BETA-BLOCKERS (ORAL)
Drug Dosage Remarks
Acebutolol Initial dose: 200 mg PO 12 hrly or 400 mg PO 24 hrly Adverse Reactions
Max dose: 1200 mg/day • CNS effects (fatigue,
Alprenolol 200-400 mg/day PO in divided doses depression, dizziness,
confusion, sleep
Atenolol1 50-100 mg PO 24 hrly or 50 mg PO 12 hrly disturbances); CV effects
Max dose: 200 mg/day (heart failure, heart block,
coldness of extremities,
Betaxolol 10-20 mg PO 24 hrly
male impotence); Resp
Max dose: 40 mg/day effects (bronchospasm in
Bisoprolol Initial dose: 5 mg PO 24 hrly susceptible patients & drugs
May increase to 10 mg/day PO w/ beta1 selectivity should
be used w/ caution in these
Max dose: 20 mg/day
patients); GI effects (N/V,
Bopindolol 0.5-2 mg PO 24 hrly diarrhea, constipation);
Carteolol 5-10 mg/day PO 24 hrly or divided 12 hrly Metabolic effects (can
produce hyper- or
Max dose: 30 mg/day hypoglycemia, changes in
Carvedilol Initial dose: 12.5 mg PO 12 hrly x 2 days serum cholesterol &
Then increase to 25 mg PO 12 hrly triglycerides)
May increase dose every 2 wk thereafter, if required up Special Instructions
to: • Contraindicated in severe
Max dose: 100 mg/day PO bradycardia, preexisting
high degree of AV block,
Celiprolol 200-400 mg PO 24 hrly sick sinus syndrome &
Labetalol Initial dose: 100 mg PO 12 hrly severe, unstable LV failure
May increase dose after 2 wk to 200-400 mg/day PO • Use w/ caution in patients
Max dose: 2400 mg/day w/ bronchospasm, asthma
or obstructive airway
Metoprolol Regular release: 50-100 mg PO 6-8 hrly diseases, 1st degree block,
Max dose: 400 mg/day depression, PVD, & patients
Extended-release: 25-100 mg PO 24 hrly on insulin
Nadolol Initial dose: 40 mg PO 24 hrly • Beta-blockers may mask the
symptoms of
May increase dose wkly up to 160 mg/day until adequate hyperthyroidism &
response is achieved hypoglycemia & may
Max dose: 240 mg/day aggravate psoriasis
Nebivolol Initial dose: 2.5-5 mg PO 24 hrly • Patients on long-term
Max dose: 10 mg/day treatment should not
discontinue abruptly; should
Oxprenolol 80-160 mg/day PO in 2-3 divided doses discontinue gradually over
May increase dose every 1-2 wk until adequate response 1-2 wk
is achieved
Max dose: 320 mg/day
1Atenolol is available in combination w/ Nifedipine.

B19
Dosage Guidelines
ACS
BETA-BLOCKERS (ORAL) (CONT’D)

Drug Dosage Remarks
Penbutolol 20 mg PO 24 hrly Adverse Reactions
May increase up to 40-80 mg/ • CNS effects (fatigue, depression, dizziness, confusion,
day sleep disturbances); CV effects (heart failure, heart
Pindolol 2.5-5 mg PO 8 hrly block, coldness of extremities, male impotence); Resp
effects (bronchospasm in susceptible patients & drugs
May increase up to 10 mg PO w/ beta1 selectivity should be used w/ caution in these
8 hrly patients); GI effects (N/V, diarrhea, constipation);
Max dose: 40 mg/day Metabolic effects (can produce hyper- or
Propranolol Regular release: hypoglycemia, changes in serum cholesterol &
Initial dose: triglycerides)
20-40 mg PO 8-12 hrly Special Instructions
May increase at wkly interval • Contraindicated in severe bradycardia, preexisting
according to patient response high degree of AV block, sick sinus syndrome &
severe, unstable LV failure
• Use w/ caution in patients w/ bronchospasm, asthma
Extended-release: or obstructive airway diseases, 1st degree block,
Initial dose: 80 mg PO 24 hrly depression, PVD, & patients on insulin
Max dose: 320 mg/day • Beta-blockers may mask the symptoms of
Sotalol Initial dose: hyperthyroidism & hypoglycemia & may aggravate
80-160 mg/day PO 24 hrly or psoriasis
divided 12 hrly • Patients on long-term treatment should not
May increase dose gradually discontinue abruptly; should discontinue gradually
at 2-3 day intervals to over 1-2 wk
80-160 mg PO 12 hrly
CALCIUM ANTAGONISTS
Drug Dosage Remarks
Benzothiazepine
Diltiazem Regular release: Adverse Reactions
Initial dose: • CV effects (depression of cardiac function,
30-60 mg PO 6-8 hrly hypotension, worsening heart failure, edema, flushing,
May gradually increase to bradycardia); GI effect (constipation); CNS effects
360 mg/day PO in divided (headache, dizziness)
doses or up to 480 mg/day, if • HR-modulating Ca antagonists (eg Diltiazem,
needed Gallopamil & Verapamil): AV dissociation, AV block,
Extended-release: bradycardia & sinus node dysfunction
120-480 mg/day PO 24 hrly or • Short-acting dihydropyridine agents should be
12 hrly avoided because they have the potential to enhance
risk of adverse cardiac events
• Contraindicated in patients w/ overt decompensated
heart failure, though vasoselective dihydropyridines (eg
Amlodipine, Felodipine) are tolerated in patients w/
decreased LVEF
• HR-modulating Ca antagonists are contraindicated in
patients w/ bradycardia, sinus node dysfunction & AV
nodal block

B20
Dosage Guidelines
CALCIUM ANTAGONISTS (CONT’D)
ACS
Drug Dosage Remarks
Dihydropyridines
Amlodipine Initial dose: 2.5-5 mg PO 24 hrly Adverse Reactions
May increase to 10 mg PO 24 hrly if needed • CV effects (depression of cardiac function,
Max dose: 10 mg/day hypotension, worsening heart failure, edema,
Benidipine 4 mg PO 12 hrly flushing, bradycardia); GI effect (constipation);
Felodipine Initial dose: 2.5-5 mg PO 24 hrly CNS effects (headache, dizziness)
Max dose: 10 mg/day • HR-modulating Ca antagonists (eg Diltiazem,
Gallopamil & Verapamil): AV dissociation, AV
Nicardipine Regular release: block, bradycardia & sinus node dysfunction
Initial dose: 10-20 mg PO 8 hrly
May increase to 20-40 mg PO 8 hrly • Short-acting dihydropyridine should be avoided
Extended-release: because they have the potential to enhance risk
40 mg PO 12 hrly of adverse cardiac events
Nifedipine1 Regular release: • Contraindicated in patients w/ overt
May increase to 20 mg PO 8 hrly decompensated heart failure, though
Extended-release: vasoselective dihydropyridines (eg Amlodipine,
Initial dose: 30 mg PO 24 hrly Felodipine) are tolerated in patients w/
May increase to 120 mg PO 24 hrly decreased LVEF
or • HR-modulating Ca antagonists are
10-40 mg PO 12 hrly contraindicated in patients w/ bradycardia,
Nisoldipine 5-10 mg PO 12 hrly sinus node dysfunction & AV nodal block
or 10 mg PO 24 hrly
May increase to 20 mg PO 12 hrly
Phenylalkylamines
Gallopamil Regular release: 25-50 mg PO 6-12 hrly
Verapamil Regular release:
Initial dose: 40-80 mg PO 6-8 hrly
Extended-release: 120-360 mg PO 24 hrly
Combination Product
Amlodipine/ Amlodipine 5 mg/Perindopril 5 mg/ Adverse Reactions
Perindopril/ Atorvastatin 10 mg • GI effects (constipation, dyspepsia, N/V, diarrhea);
Atorvastatin Amlodipine 5 mg/Perindopril 5 mg/ CNS effects (headache, dizziness, paresthesia,
Atorvastatin 20 mg asthenia); Musculoskeletal effects (myalgia,
Amlodipine 5 mg/Perindopril 10 mg/ arthralgia, back pain, joint & ankle swelling);
Atorvastatin 20 mg Metabolic effects (hyperglycemia, abnormal LFT,
Amlodipine 10 mg/Perindopril 10 mg/ increased blood creatine); CV effects (palpitations,
Atorvastatin 20 mg hypotension); Other effects (nasopharyngitis,
Amlodipine 10 mg/Perindopril 10 mg/ hypersensitivity, epistaxis, flushing, edema, visual
Atorvastatin 40 mg impairment, tinnitus, cough, dyspnea, rash, pruritus)
1 tab PO 24 hrly Special Instructions
• Use w/ caution in patients w/ collagen vascular
disease, on immunosuppressant therapy,
Allopurinol or Procainamide
• Increased risk of hypotension, hyperkalemia,
decreased renal function; interstitial lung disease
on long-term therapy
• Monitor glycemic control & LFTs periodically
• Avoid in patients w/ hypersensitivity, liver
disease, severe hypotension, hemodynamically
unstable heart failure, history of angioedema,
significant bilateral renal artery stenosis; on
Sacubitril/Valsartan
1Nifedipine is available in combination w/ Atenolol.

B21
Dosage Guidelines
ACS
DIRECT THROMBIN INHIBITORS

Drug Dosage Remarks
Argatroban 2 mcg/kg per min Adverse Reactions
via continuous IV • CV effects (chest pain, hypotension); GU effects (GU tract
infusion hemorrhage including hematuria)
Adjusted to maintain Special Instructions
the aPTT at 1.5-3 • ACT should be checked 5-10 min after bolus infusion
times baseline
• Contraindicated in patients w/ active bleeding
• Use w/ caution in patients w/ hepatic dysfunction
Bivalirudin 0.75 mg/kg IV Adverse Reactions
followed by an • Hematologic effect (bleeding); Dermatologic effects
infusion of 1.75 mg/ (hypersensitivity reactions, pain on the inj site, severe anaphylaxis);
kg/hr during the CV effects (hypertension, hypotension, bradycardia); GI effects
procedure & up to (N/V, dyspepsia); Renal effect (urinary retention); Musculoskeletal
4 hr post-procedure effect (back pain); CNS effects (headache, anxiety)
If needed, may Special Instructions
continue infusion at • Contraindicated in patients w/ active major bleeding, severe
0.2 mg/kg/hr up to renal impairment including dialysis-dependent patients
20 hr
• Use w/ caution in patients at high risk for bleeding, recent major
surgery, puncture of large blood vessels or organ biopsy, hepatic
dysfunction & moderate renal impairment
FACTOR Xa INHIBITORS
Drug Dosage Remarks
Fondaparinux UA/NSTEMI: Adverse Reactions
2.5 mg SC 24 hrly • Hematologic effects (bleeding, anemia); GI effects (N/V,
up to 8 days or until constipation, diarrhea); CV effects (edema, hypotension, chest
hospital discharge pain, PCI guiding-catheter thrombosis); CNS effects (headache,
dizziness, confusion); Dermatologic effects (rash, purpura)
• Do not administer via IM route
• Contraindicated in patients w/ significant bleeding, acute
bacterial endocarditis, hypersensitivity to the drug, severe renal
impairment & body wt <50 kg
• Use w/ caution in the elderly & in moderate renal impairment
• Avoid administration 24 hr before & 48 hr after CABG surgery
Rivaroxaban Prevention of Adverse Reactions
atherothrombotic • Hematologic effects (hemorrhage, anemia, hematoma); Hepatic
events after ACS effect (increased ALT & AST, cholestasis); CNS effects (dizziness,
w/ elevated cardiac headache, fatigue), CV effect (hypotension); GI effects (N/V,
biomarkers: 2.5 mg abdominal pain); Dermatologic effects (pruritus, rashes); Other
PO 12 hrly effects (fever, peripheral edema, postprocedural hemorrhage)
Taken w/ daily dose Special Instructions
of Aspirin 75-100 • Contraindicated in patients w/ clinically significant active
mg, or daily dose of bleeding, hepatic disease associated w/ coagulopathy that can lead
Aspirin 75-100 mg to relevant risk of bleeding
plus daily dose of
Clopidogrel 75 mg • Use w/ caution in patients w/ hemorrhagic risk, severe HTN,
or standard daily bronchiectasis, lactose or galactose intolerance, &
dose of Ticlopidine moderate-severe renal impairment

B22
Dosage Guidelines
ACS
GLYCOPROTEIN IIB/IIIA INHIBITORS
Drug Dosage Remarks
Abciximab 250 mcg/kg as IV bolus (over Adverse Reactions
1 min) • Hematologic effects (bleeding, thrombocytopenia);
Followed by 0.125 mcg/kg/ GI effects (N/V); CV effects (hypotension, bradycardia,
min as a continuous IV etc); CNS effects (headache, confusion, dizziness,
infusion abnormal vision, dysphonia, fever); Other effects (pain
Max dose: 10 mcg/min in the extremities, peripheral edema); Hypersensitivity
For stabilization of UA: reactions
Start the bolus dose, followed Special Instructions
by IV infusion up to 24 hr • Contraindicated in patients w/ active bleeding, recent
prior to the possible (<6 wk) GI or GU bleeding of clinical significance,
intervention & then stop history of CVA within the past 2 yr or CVA w/
12 hr after intervention neurologic deficit, bleeding diathesis,
For the prevention of thrombocytopenia, anticoagulant within past 7 days
ischemic cardiac complica- unless prothrombin time (PT) ≤1.2, recent (<6 wk)
tions related to PCI: Start recent surgery or trauma, intracranial neoplasm,
the bolus dose 10-60 min arteriovenous malformation, aneurysm, severe
prior to the intervention hypertension, history of vasculitis, use of IV dextran
followed by the infusion for before percutaneous transluminal coronary angioplasty
12 hr (PTCA) or intent to use IV dextran, severe renal or
hepatic impairment
• Use w/ caution in patients <75 kg, are >65 yr, history of
GI disease & those receiving thrombolytics
• Monitor platelet counts prior to therapy, 2-4 hr after
bolus & at 24 hr
Eptifibatide UA/NSTEMI: 180 mcg/kg IV Adverse Reactions
bolus over 1-2 min • Hematologic effects (bleeding, thrombocytopenia);
Followed by 2 mcg/kg/min CV effect (hypotension); Hypersensitivity reactions
continuous IV x 72 hr or (anaphylaxis, rash, urticaria)
until discharge Special Instructions
If PCI is performed during • Contraindicated in patients w/ active bleeding (except
therapy: Continue for menstrual bleeding), or active abnormal bleeding within
18-24 hr post-PCI the last 30 days, history of stroke within last 30 days,
If CABG is to be performed: history of hemorrhagic stroke, major surgery within last
Discontinue prior to 6 wk, history of bleeding diathesis, thrombocytopenia,
procedure PT >1.2 or international normalized ratio (INR) ≥2,
Max duration: 96 hr severe hypertension, major trauma, severe renal
PCI without prior treatment impairment
for UA/NSTEMI: • Use w/ caution in patients w/ moderate renal
180 mcg/kg IV bolus x impairment, hepatic dysfunction
2 doses 10 min apart
Start continuous IV infusion
after 1st bolus: 2 mcg/kg/min
IV x 18-24 hr

B23
Dosage Guidelines
ACS
GLYCOPROTEIN IIB/IIIA INHIBITORS (CONT’D)

Drug Dosage Remarks
Tirofiban UA/NSTEMI: 0.4 mcg/kg/ Adverse Reactions
min IV for 30 min • Hematologic effects (bleeding, thrombocytopenia); GI
Followed by 0.1 mcg/kg/min effect (nausea); Other effects (headache, dizziness, fever
IV infusion x at least 48 hr & chills)
Infusion can be continued Special Instructions
through angiography & • Contraindicated in patients w/ active bleeding, history
continued x 12-24 hr of intracranial hemorrhage, intracranial neoplasm,
post-angioplasty/ arteriovenous malformation or aneurysm, major
atherectomy surgery or trauma within the last mth, history of aortic
Max duration: 108 hr dissection, severe uncontrolled hypertension, acute
Angioplasty/atherectomy pericarditis, hemorrhagic retinopathy, anemia, serious
without prior treatment for hepatic impairment
UA/NSTEMI: • Use w/ caution in patients w/ recent bleeding (<1 yr),
In combination w/ Heparin, known coagulopathy, platelet disorder or history of
as an initial bolus of 10 mcg/ thrombocytopenia, low platelet count, history of
kg IV administered over cerebrovascular disease (<1 yr), recent epidural
3 min immediately prior to procedure, severe CHF, cardiogenic shock
procedure • Use w/ caution in patients w/ severe renal impairment
Followed by 0.15 mcg/kg/ (Cr clearance <30 mL/min)
min IV infusion x 36 hr • Monitor platelet count, hemoglobin, hematocrit prior
to treatment, within 6 hr following bolus or loading
dose & daily until completed
LOW-MOLECULAR-WEIGHT HEPARINS (LMWH)

Drug Dosage Remarks
Dalteparin UA: 120 U/kg SC 12 hrly x Adverse Reactions
5-8 days w/ low-dose Aspirin • Hematologic effects (hemorrhage, thrombocytopenia);
rarely hypersensitivity reactions (anaphylaxis)
• Contraindicated in patients w/ active major bleeding,
patients w/ positive in vitro test for antiplatelet Ab to
the specific Heparin, prosthetic heart valves, acute
Enoxaparin UA/non-Q-wave MI: bacterial endocarditis & drug-induced
1 mg/kg SC 12 hrly x thrombocytopenia
2-8 days w/ low-dose Aspirin • Use w/ caution in patients w/ hemophilia or other
hemorrhagic disorders (including history of
Heparin-induced thrombocytopenia), peptic ulcer,
recent cerebral hemorrhage, severe hypertension,
severe liver disease, post-major trauma or recent
Nadroparin UA/non-Q-wave MI: surgery to brain, spinal or ophthalmologic surgery,
86 U/kg SC 12 hrly x 6 days hypersensitivity to Heparin
w/ low-dose Aspirin • Consider risk vs benefit before neuraxial intervention is
employed in patients anticoagulated or to be
anticoagulated for thromboprophylaxis
• Monitoring of platelets is recommended at baseline &
periodically during treatment

B24
Dosage Guidelines
ACS
NITRATES (IV)
Drug Dosage Remarks
Glyceryl Initial dose: 5-10 mcg/min Adverse Reactions
trinitrate IV infusion after dilution • IV administration (especially if given too rapidly): May
(Nitroglycerin, Increase by 5 mcg/min every cause CV effects (severe hypotension, retrosternal
GTN, NTG) 3-5 min until some response discomfort, flushing, tachycardia); GI effects (nausea &
is noted retching, abdominal pain); CNS effects (headache,
If there is still no response dizziness, apprehension, restlessness, muscle twitching,
at 20 mcg/min: May increase syncope); Other effects (diaphoresis); prolonged
at increments of 10 mcg/min administration has been associated w/
& later if required, 20 mcg/ methemoglobinemia
min increments can be used Special Instructions
Usual dose: 10-200 mcg/min • Avoid in patients w/ severe hypotension, hypovolemia,
marked anemia, heart failure due to obstruction or
raised intracranial pressure due to head trauma or
hemorrhage
• Use w/ caution when there is a fall of SBP <110 mmHg
in normotensive patients, & fall of mean arterial
pressure >25% in hypertensive patients
• Use w/ caution in patients w/ severe renal or hepatic
dysfunction, hypothyroidism, malnutrition or
Isosorbide 2-10 mg/hr IV infusion after hypothermia
dinitrate dilution • Close monitoring of HR & BP is necessary during IV
Max dose: 20 mg/hr IV infusion
• Do not administer to patients who have taken
phosphodiesterase inhibitors within the past 24 hr
• The plastic equipment used for administration may
absorb GTN & dosing may need to be adjusted for this
• Nitrate tolerance usually develops w/ long-term use
& dosing w/ adequate nitrate-free interval is
recommended

B25
Dosage Guidelines
ACS
NITRATES (ORAL - LONG-ACTING)

Drug Dosage Remarks
Glyceryl Extended-release cap: Adverse Reactions
trinitrate 2.5 mg PO 8-12 hrly or • CNS effects (headache which usually decreases w/
(Nitroglycerin, 5 mg PO 8-12 hrly in severe long-term administration, lightheadedness, dizziness,
GTN, NTG) cases syncope); rarely CV effects (bradycardia, hypotension);
Extended-release tab: GI effects (N/V, bowel incontinence, xerostomia)
Initial dose: 2.6 mg PO • Nitrate tolerance usually develops w/ long-term use &
12 hrly dosing w/ adequate nitrate-free interval is
recommended
May increase to 6.4 mg PO
8-12 hrly Special Instructions
(Dose will depend on • Dosing to overcome nitrate tolerance: Recommend
formulation) giving last dose of short-acting agents at 7 PM;
administer 2x/day rather than 4x/day; administer
Isosorbide 20-120 mg/day PO in divided extended-release preparations once in the morning
dinitrate doses • Avoid in patients w/ severe hypotension, hypovolemia,
May increase according to marked anemia, heart failure due to obstruction or
patient response raised intracranial pressure due to head trauma or
Max dose: 240 mg/day hemorrhage
Isosorbide Regular release: • Use w/ caution in patients w/ severe renal or hepatic
5-mononitrate Initial dose: 10 mg PO dysfunction, hypothyroidism, malnutrition or
(Isosorbide 12 hrly hypothermia
mononitrate) May increase to 20-40 mg PO • Co-administration w/ phosphodiesterase inhibitors (eg
8-12 hrly depending on Sildenafil) are contraindicated
formulation
Extended-release:
depending on formulation

B26
Dosage Guidelines
ACS
NITRATES (ORAL - SHORT-ACTING)
Available
Drug Dosage Remarks
Strength
Glyceryl 400, 500 mcg Acute anginal attack: 300-600 mcg Adverse Reactions
trinitrate sublingual SL every 3-5 min until cessation of • CNS effects (headache,
(Nitroglycerin, (SL) tab pain or side effects occur lightheadedness, dizziness,
GTN, NTG) Max dose: 3 doses within 15 min syncope); rarely CV effects
Prophylaxis: (bradycardia, hypotension);
400-600 mcg SL 5-10 min prior to GI effects (N/V, bowel
activity incontinence, xerostomia)
400 mcg/dose Acute anginal attack: 1-2 sprays • Avoid in patients w/ severe
SL spray (400-800 mcg) SL every 5 min until hypotension, hypovolemia,
cessation of pain or side effects occur marked anemia, heart
Max dose: 3 doses within 15 min failure due to obstruction or
Prophylaxis: raised intracranial pressure
due to head trauma or
1 spray SL 5-10 min prior to activity
hemorrhage
500 mcg Acute anginal attack: 2-5 mg 8 hrly, • Use w/ caution in patients
buccal tab placed between gum & upper lip w/ severe renal or hepatic
If accidentally swallowed, place dysfunction,
another tablet in buccal cavity hypothyroidism,
malnutrition or
Isosorbide 5, 10 mg SL Acute anginal attack: 2.5-10 mg SL hypothermia
dinitrate tab every 5-10 min until cessation of pain • Co-administration w/
or side effects occur phosphodiesterase
Max dose: 3 doses within 15-30 min inhibitors (eg Sildenafil) is
contraindicated within 24 hr
Prophylaxis: 2.5-10 mg SL prior to
interval after taking a
activity
Nitrate preparation
1.25 mg/dose Acute anginal attack: Acute attacks:
or spray 1-3 sprays (1.25-3.75 mg) SL at 30 sec • Instruct patient to sit down
interval between sprays. Do not & use medication at 1st sign
inhale medication of angina attack
Prophylaxis: • Patient should be made
1-3 sprays (1.25-3.75 mg) SL prior to aware that dose may be
activity at 30 sec interval between repeated in 5-10 min w/
sprays. Do not inhale medication max of 3 doses given
• Patient should seek
emergency medical
treatment if pain does not
subside

B27
Dosage Guidelines
ACS
NITRATES (TOPICAL - LONG-ACTING)

Available
Drug Dosage Remarks
Strength
Glyceryl 5 mg/24 hr 5-20 mg/24 hr (1-2 Adverse Reactions
trinitrate patch patches) applied • CNS effects (headache which usually decreases
(Nitroglycerin, (0.2 mg/hr) 24 hrly usually in the w/ long-term administration, lightheadedness,
GTN, NTG) 10 mg/24 hr morning dizziness, syncope); rarely CV effects
patch To prevent (bradycardia, hypotension); GI effects (N/V,
(0.4 mg/hr) tolerance: Patch-free bowel incontinence, xerostomia)
period of 8-12 hr, • Nitrate tolerance usually develops w/ long-term
usually at night every use & dosing w/ adequate nitrate-free interval
24 hr is is recommended
recommended • Topical preparations: Contact dermatitis, local
irritation & erythema
• Dosing to overcome nitrate tolerance:
Recommend giving last dose of short-acting
agents at 7 PM; administer 2x/day rather than
4x/day; administer extended-release
preparations once in the morning
• Avoid in patients w/ severe hypotension,
hypovolemia, marked anemia, heart failure due
to obstruction or raised intracranial pressure
due to head trauma or hemorrhage
• Use w/ caution in patients w/ severe renal or
hepatic dysfunction, hypothyroidism,
malnutrition or hypothermia
• Co-administration w/ phosphodiesterase
inhibitors (eg Sildenafil) are contraindicated
OPIOID (IV)
Drug Dosage Remarks
Morphine MI: 10 mg IV at a Adverse Reactions
rate of 2 mg/min • GI effects (N/V, constipation); CV effects (hypotension,
followed by a further bradycardia); Resp effect (resp depression); CNS effects
dose of 5-10 mg IV, (drowsiness, confusion, changes in mood)
if necessary • Diamorphine may cause less nausea & hypotension than Morphine
Use half dose in Special Instructions
elderly
• Avoid IM inj
UA: 2-5 mg IV at a
rate of 2 mg/min • Antiemetics may be administered concurrently w/ opioids
May repeat every • If Morphine-induced resp depression occurs, Naloxone IV can
5-30 min as needed be administered
for symptom relief • Contraindicated in resp depression, obstructive airway disease
• Use w/ caution in acute alcoholism, convulsive disorders, head
injuries & if intracranial pressure is raised, patients w/
hypothyroidism, adrenocortical insufficiency, asthma, renal or
hepatic impairment, prostatic hyperplasia, hypotension, shock,
inflammatory or obstructive bowel disorders or myasthenia gravis

B28
Dosage Guidelines
ACS
OTHER ANTI-ANGINAL DRUGS
Drug Dosage Remarks
3-Ketoacyl-CoA Thiolase Inhibitor
Trimetazidine 40-60 mg/day PO in Adverse Reactions
divided doses • GI effects (N/V, abdominal pain, diarrhea); CNS effects have
been reported (parkinsonism, gait disorders, tremors)
• Should be taken w/ food
• Contraindicated in patients w/ known hypersensitivity,
pregnancy & lactation
Potassium Channel Activator
Nicorandil 10-20 mg PO 12 hrly Adverse Reactions
Max dose: 30 mg • CNS effects (headache which is usually transitory, weakness);
PO 12 hrly CV effects (vasodilation, flushing, hypotension, increased HR);
GI effects (N/V, oral ulcerations)
• Avoid in patients w/ cardiogenic shock, LV failure w/ low filling
pressures & hypotension
• Use w/ caution in patients w/ low SBP, hypovolemia or acute
pulmonary edema
Sodium Channel Inhibitor
Ranolazine 500 mg PO 12 hrly Adverse Reactions
Max dose: 2000 mg/ • CNS effects (dizziness, headache, vertigo); GI effects
day (constipation, N/V, abdominal pain, dry mouth); CV effects
(syncope, bradycardia, palpitations, hypotension, peripheral
edema); Other effects (tinnitus, dyspnea, hematuria)
• Use w/ caution in patients w/ renal disease, in patients w/
history of malignant neoplasms & adenomatous polyps
• Contraindicated in patients w/ significant hepatic impairment
• Avoid co-administration w/ azoles, macrolides, Nefazodone,
Nelfinavir, Rifampicin, Phenytoin, Phenobarbital,
Carbamazepine, St John’s wort

B29
Dosage Guidelines
ACS
UNFRACTIONATED HEPARIN (UFH)

Drug Dosage Remarks
Heparin UA: Adverse Reactions
Initial dose: 5,000 U IV • Hematologic effects (hemorrhage, thrombocytopenia);
Followed by: Rare hypersensitivity reactions (urticaria, angioedema,
1,000-2,000 U/hr IV anaphylaxis); Other effects that may occur w/ long-term
infusion use (osteoporosis, alopecia)
or Special Instructions
15,000 U SC 12 hrly • aPTT should be measured 6 hr after any dosage change
or • Avoid in patients w/ active major bleeding, patients w/
history of Heparin-induced thrombocytopenia
5,000-10,000 U IV 4-6 hrly
• Use w/ caution in patients w/ hemophilia or other
hemorrhagic disorders, peptic ulcer, recent cerebral
hemorrhage, severe hypertension, severe liver disease,
post-major trauma or recent surgery to brain, spinal or
ophthalmic, hypersensitivity to Heparin
• Consider risk vs benefit before neuraxial intervention is
• Monitoring of platelets is recommended at baseline &
periodically during treatment

Please see the end of this section for the reference list.
B30
Cardiovascular Disease Prevention (1 of 15)
1
EVALUATION ON ROUTINE PHYSICIAN VISIT
Patients ≥20 years old:
• Risk factor assessment for cardiovascular disease (CVD)
Patients ≥40 years old:
• Assessment of absolute risk of CVD
2
LOW-MODERATE RISK RISK
A Patient education No STRATIFICATION
B Is the patient at high risk
Lifestyle modification
for a future CV
event?
Yes
HIGH-VERY HIGH RISK

A Patient education
B Lifestyle modification
C Management of other risk factors
D Pharmacological therapy No
EVALUATION
• Antiplatelet agent Does patient have coronary
Primary
heart disease (CHD) or other
• Lipid-lowering agent Prevention
vascular disease?
Yes
Secondary
Prevention
D Pharmacological therapy
• Antiplatelet agent/anticoagulant
• Antihypertensive agent
• Lipid-lowering agent
• Vaccination
B31
1 EVALUATION ON ROUTINE PHYSICIAN VISIT

• Atherosclerotic cardiovascular disease (ASCVD) risk assessment is essential for primary prevention
• For patients 20-39 years old, traditional ASCVD risk factors may be assessed at least every 4-6 years
• Patients ≥40 years old should be evaluated for the absolute risk of CVD at every routine physician visit
• Patients 20-39 years old & those between 40-59 years old w/ low 10-year ASCVD risk (<7.5%) may be assessed
for long-term/lifetime risk
Risk Factor Assessment for CVD
History
• Conventional risk factors include age, smoking, sedentary lifestyle, unhealthy diet (eg salt & fat intake),
overweight/obesity, hypertension, diabetes mellitus (DM), hypercholesterolemia or combination of clinical
entities like metabolic syndrome
• Current symptoms of atherosclerosis [eg angina, intermittent claudication, myocardial infarction (MI), transient
ischemic attack (TIA), or stroke]
• Personal history of polycystic ovary syndrome, gout, chronic inflammatory conditions, sexual dysfunction,
kidney disease, periodontitis
CVD PREVENTION
• Use of drugs known to raise blood pressure (eg oral contraceptives, NSAIDs, licorice, cocaine, amphetamine,
Erythropoietin, Ciclosporin, & steroids)
• Family history of high blood pressure (BP), DM, dyslipidemia, coronary heart disease (CHD), stroke, renal
disease & premature CVD
- Risk of CHD increases as number of family members w/ CHD increases & the younger the age at which
family members develop the disease (<55 years of age in 1st-degree male relatives or female relatives <65
years old)
• Personal, psychosocial, occupational & environmental factors that can influence long-term care (eg depression,
anxiety, type D personality, lack of social support, social isolation, & stressful conditions at work)
• Alcohol consumption
Physical Exam
• BP, pulse rate, ankle-brachial index (ABI)
• Height, weight, waist circumference
- Calculate body mass index (BMI) by dividing patient’s weight (kg) by the square of the height (m2)
• Comprehensive physical examination
- CV: Heart size, apex beat displacement, signs of heart failure, disease in the carotid, renal & peripheral
arteries, coarctation of aorta
- Lungs: Signs of congestion or lung disease
- Abdomen: Bruits, enlarged kidneys, liver & other masses
- Eyes: Optic fundi
- CNS: Evidence of CVD & complications of diabetes (ie neuropathy)
• Examination for features of secondary hypertension (pheochromocytoma, Cushing’s syndrome)
Diagnostic Tests
• May include a complete blood count (CBC), fasting blood glucose &/or HbA1c, serum lipids [total cholesterol
(TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) & triglycerides
(TG)], sodium, potassium, uric acid, creatinine & estimated glomerular filtration rate (eGFR), liver function
tests (LFTs), urinalysis, 12-lead ECG
• A chest X-ray may help in the detection of cardiomegaly & early pulmonary findings of heart failure
The following should be performed based on patient’s risk for dyslipidemia & diabetes (at least every 5
years or more frequent if risk factors are present)
• Fasting serum lipoprotein profile
- If patient has not fasted prior to lipid profile: TC & HDL-C can still be measured
• Fasting blood glucose
• High-sensitivity C-reactive protein may be considered in intermediate- to high-risk patients w/ LDL-C levels
of <130 mg/dL that need further stratification
• The following are not recommended for routine use but may be considered in select patients: Homocysteine
level & lipoprotein (a) level, DNA-based tests, any serological or urinary biomarkers
Imaging Studies
• Coronary artery calcification (CAC) measurement & carotid intima-media thickness (CIMT) test may help
in choosing best treatment strategy for patients
- CAC scoring is the best imaging modality to improve stratification of CVD risk
• Echocardiography may be performed in patients w/ breathlessness or hypertension
• Exercise stress testing may be considered in the CV assessment of an asymptomatic individual w/ an
interpretable resting ECG, a high CAD pre-test likelihood, & an intermediate to high CV risk
Coronary Risk Charts for Determination of CVD Risk
• Age, gender, smoking status, DM, BP, & lipid levels are used to determine the CVD risk
• Overall CVD risk is more important than the presence or absence of specific risk factors
B32
1 EVALUATION ON ROUTINE PHYSICIAN VISIT (CONT’D)

Coronary Risk Charts for Determination of CVD Risk (Cont’d)
• Risk assessment tools that may be used to estimate CVD risk for patients who have not experienced symptomatic
CVD or other atherosclerotic diseases include Framingham Risk Assessment Tool, Multi-Ethnic Study of
Atherosclerosis (MESA) 10-year ASCVD risk w/ coronary artery calcification calculator, Systematic Coronary
Risk Estimation (SCORE), Reynold’s Risk Score, & United Kingdom Prospective Diabetes Study (UKPDS) risk
engine in individuals w/ type 2 DM
• After estimating the 10-year fatal & non-fatal CVD risk in apparently healthy individuals, the following should
be considered: Risk modifiers (ethnicity, family history, genetics, frailty, body composition, psychosocial factors,
socioeconomic determinants, environmental factors, blood or urine biomarkers, imaging findings), lifetime
risk & treatment benefit, polypharmacy & patient preferences
2 RISK STRATIFICATION
Major Risk Factors
CVD PREVENTION
• Age (men ≥45 years; women ≥55 years)
• Cigarette smoking
• Apolipoprotein-B-containing lipoproteins (most abundant of which is LDL)
- Primary hypercholesterolemia [LDL-C 160–189 mg/dL (4.1–4.8 mmol/L); non-HDL-C 190–219 mg/dL
(4.9–5.6 mmol/L)]
• Increased serum total cholesterol level
• Chronic kidney disease (CKD)
• Diabetes mellitus
- For individuals w/ high HDL-C (>60 mg/dL), subtract 1 risk factor from the total
- History of gestational diabetes in women
• Hypertension (elevated BP or on antihypertensive medication)
- History of preeclampsia or pregnancy-induced hypertension in women
• Metabolic syndrome
• Family history of premature ASCVD (male 1st-degree relative <55 years; female 1st-degree relative <65 years)
Additional Risk Factors
• Dyslipidemic triad (hypertriglyceridemia; low HDL-C; & an excess of small, dense LDL-C)
• Fasting/postprandial hypertriglyceridemia
• Family history of hyperlipidemia
• Obesity, abdominal obesity
• Elevated apo B
• Elevated LDL particle number
• Elevated small dense LDL-C
• Polycystic ovarian syndrome (PCOS) in women
• History of premature menopause
• South Asian ancestry
Nontraditional Risk Factors
• Elevated lipoprotein (a)
• Elevated clotting factors
• Elevated inflammation markers, eg high-sensitivity C-reactive protein (CRP)
• Chronic inflammatory conditions, eg HIV, psoriasis, rheumatoid arthritis
• Elevated triglyceride-rich remnants
• Elevated homocysteine levels
• Apo E4 isoform
• Elevated uric acid
• ABI <0.9
Patients w/ the following conditions are considered CHD risk equivalents:
• Type 2 DM
- There was insufficient evidence to support type 1 DM as a CHD risk equivalent, although type 1 DM w/
proteinuria may increase the risk for ischemic CVD
• Patients w/ other forms of symptomatic atherosclerotic disease, such as peripheral arterial disease (PAD),
abdominal aortic aneurysm (AAA), & symptomatic carotid artery disease
• Large-vessel atherosclerotic ischemic stroke
• Framingham Heart Score risk ≥20%
Note that CVD risk may be higher than indicated in the coronary risk chart in the following:
• Patients approaching the next age, BP or cholesterol category
• Sedentary or obese patients
• Those w/ family history of premature CHD or stroke in a 1st-degree relative (male <55 years; female <65 years)
• Patients w/ low HDL-C or high TG
• Patients w/ DM or impaired glucose tolerance
• Those already on antihypertensive therapy
• Patients w/ evidence of preclinical atherosclerosis
B33
2 RISK STRATIFICATION (CONT’D)
CVD RISK CATEGORIES

ACC/AHA 2019 ESC 2021
Risk
Category 10-Year ASCVD Apparently Healthy Patients w/ Risk Factors
Risk1 Individuals2
Very High No • < 50 years: ≥7.5% • D ocumented clinical ASCVD [eg previous
Risk recommendation • 50-69 years: ≥10% acute myocardial infarction (AMI), acute
• ≥70 years: ≥15% coronary syndrome (ACS), coronary
revascularization & other arterial
revascularization procedures, TIA & stroke,
aortic aneurysm & PAD] or unequivocally
documented ASCVD finding (eg significant
plaque) on imaging that does not include
CVD PREVENTION
some increase in continuous imaging

parameters (eg intima-media thickness of
the carotid artery)
• T2DM w/ established ASCVD &/or severe
target organ damage (TOD)3
• Without diabetes or ASCVD but w/ severe
CKD (eGFR <30 mL/min/1.73 m2) or eGFR
30-44 mL/min/1.73 m2 & albumin-to-
creatinine ratio (ACR) >30
High Risk ≥20% • < 50 years: 2.5-<7.5% • T 2DM without ASCVD &/or severe TOD w/
• 50-69 years: 5-<10% moderate risk criteria not met3
• ≥70 years: 7.5-<15% • Without diabetes or ASCVD but w/ moderate
CKD (eGFR 30-44 mL/min/1.73 m2) & ACR
<30 or eGFR 45-59 mL/min/1.73 m2 & ACR
30-300 or eGFR ≥60 mL/min/1.73 m2 & ACR
>300
• Familial hypercholesterolemia (FH)
associated w/ markedly increased levels of
cholesterol
Moderate No • < 50 years: <2.5% • P
atients w/ <10 years of well-controlled
Risk recommendation • 50-69 years: <5% T2DM without TOD or other ASCVD risk
• ≥70 years: <7.5% factors3
Intermediate 7.5% to <20% No recommendation
Risk
Borderline 5% to <7.5% No recommendation
Risk
Low Risk <5% • < 50 years: <2.5%
• 50-69 years: <5%
• ≥70 years: <7.5%
T2DM = Type 2 Diabetes Mellitus
1ASCVD risk estimator (http://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calculate/estimator/)
estimates the 10-year ASCVD risk for asymptomatic individuals 40-75 years old.
2Based on SCORE2 & SCORE2-Older Persons (SCORE2-OP)
SCORE2 estimates the 10-year risk of fatal & non-fatal CVD events (eg stroke, MI) in apparently healthy
individuals 40-69 years old w/ risk factors that are not treated or have been stable for several years; can be
accessed in the ESC CVD Risk Calculation app.
SCORE2-OP estimates the 5- & 10-year fatal & non-fatal CVD events (eg stroke, MI) adjusted for
competing risks in apparently healthy individuals ≥70 years old.
3Patients >40 years old w/ type 1 DM may also be classified according to these criteria.
References:
• Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the primary prevention of
cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. Circulation. 2019.
• Visseren FLJ, Mach F, Smulders YM, et al; ESC National Cardiac Societies, ESC Scientific Document
Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021.
B34
PRINCIPLES OF THERAPY
CVD development is closely related to lifestyle characteristics & associated risk factors. There is overwhelming
scientific evidence that lifestyle modifications & reduction of risk factors can slow the development of CVD
both before & after the occurrence of a CV event.
CVD Prevention
• Primary prevention is aimed at the healthy population & population at risk (w/ ≥1 CV risk factors) that has
not had a CV event while secondary prevention is instituted for those who have confirmed CVD or had a first
index CV event
• Prevention & treatment goals are intensified based on the patient’s risk modifiers, 10-year CVD risk, lifetime
CVD risk & benefit of treatment, comorbidities, frailty & patient preferences
- Lifetime CVD risk can be estimated in apparently healthy individuals, patients w/ established ASCVD &
people with type 2 DM w/ specific lifetime CVD risk scores or can be approximated w/ age, level of risk
factor, risk modifiers, etc
Selection of Patients for Clinical Intervention
• For high- to very high-risk patients as well as those w/ established ASCVD &/or DM, intensive lifestyle
CVD PREVENTION
modification & appropriate drug treatment are required
- Monitor risk profile every 3-6 months
- High-risk patients intolerant of statin therapy should be given non-statin agents (Ezetimibe, monoclonal
antibodies, bile acid sequestrants, phytosterols)
• For low- to moderate-risk patients, treatment of risk factor is generally not recommended
- Moderate-risk patients require monitoring of risk profile every 6-12 months
- Low-risk patients may be given conservative management, focusing on lifestyle interventions
A PATIENT EDUCATION
• Counseling should be part of the patient encounter as they tend to respond more favorably
- Inform the patient that multiple risk factors contribute to atherosclerosis which causes CVD; therefore, the
aim is to decrease the total risk from all these factors
- If a goal w/ a risk factor cannot be reached, this can be remedied by more reduction in other risk factors
• Counseling regarding a healthy & physically active lifestyle is the foundation of primary prevention & has the
potential to either reduce or prevent the development of risk factors
• It would help to include family members in the educational process so they can assist the patient in achieving
lifestyle modifications
• Develop a plan to make the patient part of the management through shared decision making & hold discussions
over time so that patient is not overwhelmed by changing several behaviors all at one time (eg smoking, diet,
exercise, etc)
- Approach to care should be team-based & social determinants of health should be evaluated for ASCVD
prevention
• Re-educate the patient about proper food selection, stress management, the importance of an active lifestyle
& maintenance of ideal body weight
• Monitor progress through follow-up contact & have regular re-evaluation & behavioral interventions to
maintain adherence
• As continuous medical management is required for patients w/ CVD & its risk factors, inform patients regarding
telehealth services which may be used to ensure access to healthcare providers during the COVID-19 pandemic
B LIFESTYLE MODIFICATION
• Medical nutrition therapy, physical activity & comprehensive lifestyle approaches have been shown to improve
the control of modifiable risk factors & intermediate markers of CVD risk
Diet Modification1
• Counsel the patient on a balanced diet consisting of fruits, vegetables, low-fat dairy products, fiber, whole
grains & protein sources that are low in trans-fat, saturated fat & cholesterol:
- Total dietary intake of fats 25-35% of calories consumed
- Intake of saturated fats <7% of the total calories
- Intake of polyunsaturated fats <10% of the calories
- Monounsaturated fatty acids <20% of the caloric intake
- Limit trans fats <1% of total calories
- Intake of dietary cholesterol <200 mg/day
- Dietary options can be added (plant stanols/sterols 2 g/day; soluble fiber 30-45 g/day)
• Replace saturated fats w/ monounsaturated & polyunsaturated fats from vegetable or marine sources
- Polyunsaturated fat showed slightly greater LDL-C reductions compared to monounsaturated fat
• Minimize intake of beverages & foods w/ added sugar
1Dietary recommendations may vary between countries. Please refer to available nutritional guidelines from local health authorities.
B35
B LIFESTYLE MODIFICATION (CONT’D)

Diet Modification1 (Cont’d)
• The Prospective Urban Rural Epidemiology (PURE) study recently showed that high carbohydrate intake (>60%
of energy) was associated w/ an adverse effect on total & non-cardiovascular disease mortality whereas a high
fat intake (including saturated & unsaturated fatty acids) was associated w/ lower risk of total mortality,
non-cardiovascular disease mortality & stroke
- Limit overall carbohydrate intake especially from refined sources
• Recommended intake of sodium is <5 g/day for the general population
- Advise about the hidden salt content in processed foods
• Consumption of unsalted nuts by 30 g/day may help reduce CVD risk
• Increase consumption (≥2 servings per week) of fish high in omega-3 fatty acids
- Intake of 2-4 g daily of fish oil can reduce triglycerides by ≥25%
- The American Heart Association finds it reasonable to give omega-3 polyunsaturated fatty acid supplementation
for the secondary prevention of CHD & sudden cardiac death in patients w/ prevalent CHD or HF
• Food portions may be reduced by using a 9-inch plate w/ half of the plate composed of vegetables & fruits &
the other half divided between carbohydrates & proteins
CVD PREVENTION
• Patients w/ CVD or identified risk factors, such as diabetes, dyslipidemia, hypertension or obesity, may benefit
from personalized diet advice or referral to a dietitian
Increased Physical Activity
• Contributes to weight loss, glycemic control, improved BP, lipid profile & Insulin sensitivity
• All should be encouraged to have moderate-intensity aerobic activity (such as brisk walking) at least 30-60
minutes per day, 5-7 days a week, or 15 minutes per day for 5 days/week of high-intensity aerobic activity (such
as jogging or swimming), or a combination of the two, in addition to increase in daily lifestyle activities (like
household work, gardening & walking breaks during work)
- Resistance training may be advised at least 2 days a week
• Patients w/ CVD or CVD equivalents should be assessed prior to beginning a vigorous physical activity for
conditions that might contraindicate certain types of exercise or predispose to injury
Moderation of Alcohol Consumption
• Alcohol consumption above 3 units per day increases BP, risk of cardiac arrhythmias, cardiomyopathy &
sudden death
• Patients should be advised to abstain from alcohol or reduce alcohol consumption
• Goal: Limit alcohol intake to 100 g/week; <2 glasses per day or 20 g/day of alcohol for men & one glass per
day or 10 g/day for women
Smoking Cessation
• Studies have shown that smoking accelerates coronary plaque development & may lead to plaque rupture,
dangerous in patients w/ advanced coronary atherosclerosis
• Smoking cessation has been shown to significantly increase HDL-C
• Evidence supports the beneficial effect of smoking cessation on CHD mortality
• All smokers should be strongly encouraged to quit smoking by a health professional & be supported in their
efforts to do so
- Assess the tobacco user’s willingness to quit
- Assist by counseling & developing a plan for quitting
- Pharmacologic intervention (such as Nicotine replacement therapy, Bupropion or Varenicline) should be
given to motivated smokers who failed to quit by counseling
- The use of electronic cigarettes as a tool for smoking cessation is not recommended due to insufficient
evidence & potential harm
- Arrange follow-up & referral to special programs
- Successful smoking cessation program often entails a multidisciplinary approach
• All nonsmokers should be encouraged not to start smoking
• Goal: Complete smoking cessation & no exposure to environmental tobacco smoke
• Please see Smoking Cessation disease management chart for further information
Weight Management
• Weight reduction results in lower BP, lower LDL-C & TG, higher HDL-C & improvements in hyperinsulinemia
& hyperglycemia; it is recommended in overweight & obese patients
- Initial target for weight loss is 5-10% for patients w/ BMI 20-25 kg/m2
• Goal BMI for Asian adults: 18.5-22.9 kg/m2
• Weight control can be achieved by a healthy diet maintained over time, increase in physical activity, structured
exercises & behavioral programs
• Successful weight reduction requires sustained personal & family motivation, & w/ long-term professional support
- Obesity also contributes to other CHD risk factors (such as hypertension, dyslipidemia, type 2 DM)
- The presence of abdominal obesity particularly raises & independently predicts CV risk & waist circumference
along w/ waist:hip ratio should be evaluated
- Waist:hip ratio is indicative of central obesity
- Gender-specific waist circumference cutoff points for increased CVD risk have been established in Asians:
≥80 cm in women & ≥90 cm in men
• Pharmacological intervention is an option for patients who are determined to lose weight & will be able to
incorporate the therapy w/ comprehensive lifestyle intervention strategies
B36
C MANAGEMENT OF OTHER RISK FACTORS

BP Control
• Goal1: BP <140/90 mmHg in all patients, though BP targets should be individualized
- Target SBP range to 130-139 mmHg in individuals ≥65 years old
- DBP <80 mmHg is recommended in all treated patients
• BP should be recorded at each visit
• Start lifestyle modification in all patients: Weight reduction, eating fruits, vegetables & low-fat dairy products,
reducing salt intake, supplementing w/ dietary potassium (3.5-5 g/day), limiting alcohol intake, & increasing
physical activity
• If BP goals are not achieved w/ lifestyle modifications, start drug therapy individualized for each patient,
considering age, race or need for drugs w/ specific benefits, CVD risk, or presence of hypertension-mediated
organ damage
• Angiotensin-converting enzyme (ACE) inhibitors & angiotensin receptor blockers (ARBs) as well as calcium
channel blockers, thiazide or thiazide-like diuretics &, for certain indications, beta-blockers are commonly
CVD PREVENTION
used in the treatment of CV disorders, eg hypertension, coronary artery disease & congestive heart failure
- Risk of COVID-19 infection or risk of developing severe COVID-19 complications is not increased w/ prior
or current treatment w/ ACE inhibitors or ARBs thus treatment should be continued as prescribed
Lipid Management
• Reduction of plasma TC by 10% decreased the incidence of CAD by 25% after 5 years, & a reduction of LDL-C
by 40 mg/dL (1 mmol/L) was accompanied by 20% reduction in CHD events
• Goal for LDL-C based on risk groups:
- Low risk <116 mg/dL (<3 mmol/L)
- Moderate risk <100 mg/dL (<2.6 mmol/L)
- High risk <70 mg/dL (<1.8 mmol/L)
- Very high risk <55 mg/dL (<1.4 mmol/L)
- If LDL-C goals based on risk groups cannot be achieved, aim to decrease LDL-C by ≥50% from baseline &
reduce other risk factors
• General goal:
- TC <200 mg/dL (<5.18 mmol/L)
- HDL-C as high as possible but at least >40 mg/dL (>1.0 mmol/L) in men & >45 mg/dL (>1.2 mmol/L) in
women
- TG <150 mg/dL (<1.69 mmol/L)
- If TG is ≥200 mg/dL (≥2.26 mmol/L), non-HDL-C should be <130 mg/dL (<3.37 mmol/L) or <100 mg/dL
(<2.59 mmol/L) for very high-risk individuals
- Apo B <90 mg/dL in high-risk patients, <80 mg/dL in very high-risk patients w/ established ASCVD or DM
w/ ≥1 additional risk factor, & <70 mg/dL in extreme-risk patients
• Therapeutic lifestyle changes should be advised to all patients above the goal range
• Stress the importance of smoking cessation, weight reduction & physical activity
• Lipid-lowering therapy may be initiated
- Secondary causes of dyslipidemia (such as hypothyroidism, alcohol abuse, Cushing’s syndrome, diseases of
liver & kidneys) should be ruled out before initiating therapy
- Statins are usually used in both primary & secondary CVD events in high-risk patients
- First drugs of choice in high-risk patients w/ hypertriglyceridemia for decreasing CVD risk
- May be considered for primary prevention in patients ≥70 years old if at high risk or above
- First-line therapy in patients ≥75 years old w/ clinical ASCVD unless contraindicated
- Initiation of statin therapy is recommended for patients 40-75 years w/ LDL-C of 70-189 mg/dL without
clinical ASCVD or DM, patients ≥21 years of age w/ primary LDL-C ≥190 mg/dL, & patients 40-75 years
w/ DM
- Fibrates have not been found to reduce CV events but may be used in the treatment of severe
hypertriglyceridemia
- Individuals w/ TG >500 mg/dL should be started w/ fibrate in addition to statin to prevent acute pancreatitis
• Current evidence shows that lipid-lowering therapy is safe in patients w/ COVID-19 infection
- Lipid-lowering therapy should be continued in patients w/ confirmed COVID-19 diagnosis & abnormal LFTs
unless alanine transaminase (ALT) or aspartate transaminase (AST) progressively increases, a significant
drug-drug interaction between the lipid-lowering agents & COVID-19 drugs has been identified, or patient
is critically ill &/or cannot take oral medications
- Bile acid sequestrants & Niacin may be temporarily discontinued in patients w/ COVID-19 infection due to
the lack of evidence of CV outcome data
1Recommendations for BP treatment goals may vary between countries. Please refer to available guidelines from local health authorities.
B37
C MANAGEMENT OF OTHER RISK FACTORS (CONT’D)

Diabetes Management
• Diabetic patients (type 1 or type 2) are at increased risk for CVD & have worse outcomes after surviving a CVD
event
• Good glycemic control substantially reduces the risk of CV events & microvascular diseases
• Treatment of DM is always recommended regardless of the overall risk of vascular disease
• Start appropriate therapy to achieve near-normal fasting plasma glucose (<7 mmol/L) or as indicated by near-normal
HbA1c, starting w/ a healthy diet & exercise
• The goal, in general, is HbA1c <7% (<53 mmol/mol) for both type 1 & 2 DM, but since HbA1c may vary w/
patients’ ethnicity/race, values must be individualized
- A HbA1c goal of ≤6.5% (≤48 mmol/mol) should be considered in type 2 DM patients w/ good health status
& without ASCVD
- To reduce the risk of hypoglycemia, individualize glycemic goals based on patient’s profile
• Lifestyle modification w/ BP & lipid management are recommended in all diabetic patients
- If lifestyle modification fails, oral antidiabetic medications, preferably Metformin followed by consideration
CVD PREVENTION
of a sodium-glucose co-transporter 2 inhibitor (SGLT2) or a glucagon-like peptide-1 (GLP-1) receptor agonist,

or Insulin should be added to the treatment regimen
• Lipid-lowering drugs are recommended for all type 2 DM patients & for type 1 DM patients >40 years old
- May be considered in patients <40 years at high risk w/ multiple risk factors & microvascular
complications
• Patients w/ diabetes require strict blood glucose monitoring & prevention of diabetes complications during
the COVID-19 pandemic in order to keep their susceptibility low & to prevent severe COVID-19 disease courses
- Current evidence suggests that dipeptidyl peptidase-4 enzyme inhibitors & Insulin can be safely used in
diabetic patients w/ COVID-19 infection
- Avoid sulfonylurea, thiazolidinediones & SGLT2 inhibitors in patients w/ severe COVID-19 infection
Obesity/Overweight Management
• Weight loss is indicated for patients w/ WHO BMI >30 kg/m2 or 25-29.9 kg/m2 w/ risk factors (eg DM,
prediabetes, hypertension, dyslipidemia, waistline >88 cm for women/>102 cm in men) or obesity-associated
comorbidities
• Goal is 5-10% weight loss in 6 months & weight maintained within 2 years
• Lifestyle modifications (diet modification, increased physical activity, weight management) are recommended
in all obese/overweight patients
- Comprehensive lifestyle intervention is recommended if no weight loss is seen w/ lifestyle modifications
• Preventive measures including lifestyle modifications decrease the risk of cardiometabolic diseases which in
turn reduce the risk of severe COVID-19 infection
• Addition of pharmacological therapy is recommended if patient continues to gain weight or is unable to lose
weight even w/ comprehensive lifestyle interventions
• May refer patients for bariatric surgery if all interventions fail & patient has a BMI ≥40 kg/m2 or BMI ≥35 kg/
m2 w/ comorbidities
• Please see Obesity disease management chart for further information
Cardiac Rehabilitation
• Comprehensive outpatient cardiovascular rehabilitation program is recommended in patients w/ ACS, chronic
angina, post coronary artery bypass surgery (CABG) or post percutaneous coronary intervention
- It is recommended for patients after ASCVD events &/or revascularization & those w/ heart failure (particularly
heart failure w/ reduced ejection fraction) to have an exercise-based cardiac rehabilitation & prevention
program to improve patient outcomes
Depression Management
• Screening for depression is advisable in patients w/ recent CABG or MI
• Management of depression has not been shown to improve CVD prognosis but may be advisable for its other
clinical effects
D PHARMACOLOGICAL THERAPY
Antiplatelet Agents
• Antiplatelet agents have been shown to reduce vascular mortality, nonfatal reinfarction of the myocardium,
nonfatal stroke in patients w/ unstable angina (UA), AMI, stroke, TIAs or other evidence of CVD
Aspirin
Primary prevention
• Low-dose Aspirin (75-100 mg/day) should not be routinely used for primary prevention of ASCVD in patients
>70 years old & in adults of any age w/ increased risk of bleeding
- May be considered for primary prevention of ASCVD in select patients 40-70 years old w/ high ASCVD risk
but without bleeding risk & in patients w/ DM at high or very high CVD risk without contraindications
- Risk-benefit profile should be assessed before using Aspirin for primary prevention especially in patients w/ DM
B38
D PHARMACOLOGICAL THERAPY (CONT’D)

Antiplatelet Agents (Cont’d)
Aspirin (Cont’d)
Primary prevention (Cont’d)
• Recommended for use in men >45 years, primarily to protect against MI; & women >55 years, primarily to
protect against stroke
Secondary prevention
• Good evidence shows that Aspirin therapy (75-100 mg/day) can prevent MI, stroke & vascular death in men
& women w/ established CVD
• Low dose or 75 mg/day is recommended for the high-risk group or individuals w/ >20% risk of MI & stroke,
& in diabetic patients
• Other groups recommend Aspirin in all patients w/ established CVD (eg previous MI or revascularization) &
in patients without a history of CVD but w/ >10% 10-year CVD risk
- Low-dose Aspirin given indefinitely is recommended in patients w/ established CVD & after a TIA or stroke,
unless contraindicated
CVD PREVENTION
• Long-term secondary prevention w/ Aspirin & a second antithrombotic drug (a P2Y12 inhibitor or low-dose
Rivaroxaban) should be considered in patients whose risk for ischemic events is high & risk for bleeding is low
Clopidogrel
• Recommended in combination w/ Aspirin in UA/NSTEMI patients wherein Ticagrelor or Prasugrel is unavailable
or contraindicated
- Initial dose of 300 mg followed by 75 mg daily for at least 1 month & ideally up to 12 months
• Recommended as an alternative to Aspirin in patients intolerant of Aspirin & may be considered in preference
to Aspirin in those w/ established ASCVD
• Recommended in patients w/ TIA or non-cardioembolic ischemic stroke
Prasugrel
• Recommended in combination w/ Aspirin only in P2Y12-inhibitor-naive patients (especially diabetics) in whom
coronary anatomy is known & who will undergo PCI
- Initial dose of 60 mg to be given at the time of PCI, followed by 10 mg daily for 12 months
Ticagrelor
• Recommended in combination w/ Aspirin in UA/NSTEMI/STEMI patients w/ intermediate to high risk of
ischemic events regardless of choice of therapy (invasive or conservative)
- Initial dose of 180 mg then 90 mg 12 hourly for 12 months
Vorapaxar
• A protease activated receptor-1 (PAR-1) antagonist that inhibits platelet activation
• Studies showed that Vorapaxar, when given w/ other antiplatelet agents, significantly reduced incidences of
Anticoagulants
• For COVID-19 patients requiring oral anticoagulant therapy, drug-drug interactions between oral anticoagulants
& COVID-19 drugs as well as liver & renal function should be considered in order to decrease the risk of
bleeding or thromboembolic complications
Warfarin
• May be used in post-MI patients for stroke prevention when clinically indicated (such as atrial fibrillation or
LV thrombus, dilated LV w/ poor systolic function)
• May be considered for paroxysmal or chronic atrial fibrillation or atrial flutter
• Warfarin w/ either Aspirin or Clopidogrel increases risk of bleeding & should be monitored closely by checking
PT/INR
• Monitor international normalized ratio (INR) when using Warfarin
Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)1
• Also called novel oral anticoagulants, new oral anticoagulants or direct oral anticoagulants
• Direct-acting inhibitors of either thrombin (Dabigatran) or factor Xa (Apixaban, Edoxaban, Rivaroxaban)
• May be used in the prevention & treatment of VTE & in the prevention of stroke & systemic embolism in
patients w/ ACS & non-valvular atrial fibrillation
Antihypertensive Agents2
• Initiation of drug therapy3 is recommended for patients w/ a BP of ≥130/80 mmHg & ≥10% estimated 10-year
ASCVD risk, & those w/ a BP of ≥140/90 mmHg & <10% estimated 10-year ASCVD risk
• Include ACE inhibitors or ARBs w/ calcium channel blockers, thiazide diuretics or beta-blockers, either alone
or in combination
• If BP is uncontrolled despite treatment w/ 3 antihypertensive medications at maximally tolerated doses, consider
adding an aldosterone antagonist, an alpha blocker, a centrally acting agent or a vasodilator
1Please see Ischemic Stroke, Venous Thromboembolism - Management & Venous Thromboembolism - Prevention disease management
charts for specific dosing recommendations.
2Many antihypertensive agents are available. Please see Hypertension disease management chart for specific dosing recommendations.
3Recommendations for treatment initiation may vary between countries. Please refer to available guidelines from local health authorities.
B39
D PHARMACOLOGICAL THERAPY (CONT’D)

Lipid-lowering Agents1
• Include statins, fibrates, bile acid binding resins, Niacin, anti-sense apolipoprotein B oligonucleotide
(Mipomersen), microsomal transfer protein inhibitor (Lomitapide), PCSK9 inhibitors & selective cholesterol
absorption inhibitors (Ezetimibe)
• May halt progression or induce regression of coronary atherosclerosis
• Statins are drugs of choice & have been shown not only to reduce hyperlipidemia but also to reduce CV events
& mortality
- A high-intensity statin is recommended to be given at the highest tolerated dose to achieve the LDL-C goals
set for a specific risk group
• Use of statin therapy may benefit patients who undergo coronary artery bypass grafting (CABG), preoperatively
& postoperatively
• Statin therapy recommendations per target LDL-C reductions as follows:
- High-intensity statin therapy [eg Atorvastatin (80 mg), Rosuvastatin (20 mg)] for approximately ≥50% LDL-C
CVD PREVENTION
reduction
- May be given to patients w/ ≥20% 10-year ASCVD risk
- Moderate-intensity statin therapy [eg Atorvastatin (10 mg), Rosuvastatin (10 mg), Simvastatin (20-40 mg),
Pravastatin (40 mg), Lovastatin (40 mg), Fluvastatin (40 mg 12 hrly), Pitavastatin (1-4 mg)] for goals of <50%
lower LDL-C levels
- May be given to patients w/ 7.5-19.9% 10-year ASCVD risk
- Low-intensity statin therapy [eg Simvastatin (10 mg), Pravastatin (10-20 mg), Lovastatin (20 mg), Fluvastatin
(20-40 mg)] for <30% reduced LDL-C levels
• If LDL-C goals are not reached, it is recommended to combine a maximally tolerated statin dose w/ Ezetimibe
PCSK9 Inhibitors
• Eg Alirocumab, Evolocumab
• Indicated for the prevention of CV events
- Alirocumab reduces the risk of MI, stroke, & unstable angina requiring hospitalization in patients w/
established CVD
- Evolocumab reduces the risk of MI, stroke, peripheral arterial disease, & coronary revascularization in
patients w/ established ASCVD
• Recommended in patients w/ FH who are intolerant of statins or in very high-risk FH patients whose treatment
w/ a maximally tolerated statin dose plus Ezetimibe did not achieve target goal
• As human monoclonal antibody, it inhibits the binding of PCSK9 to low-density lipoprotein receptors (LDLRs)
thus increasing the number of available LDLRs to clear LDL thereby decreasing LDL-C concentration
• Alirocumab may be given as an adjunct to diet, alone or in combination w/ other lipid-lowering therapies
• Evolocumab may be given as an adjunct to diet & correction of other risk factors: In combination w/ the
maximum tolerated dose of a statin w/ or without other lipid-lowering therapies, or alone or in combination
w/ other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated
Other Agents
• Colchicine at a low dose (0.5 mg/day) may be considered in secondary prevention of CVD, particularly if other
risk factors are insufficiently controlled or if recurrent CVD events occur w/ optimal therapy
Vaccination
• Patients w/ CVD or other atherosclerotic vascular disease (such as PAD, CAD) should have an annual influenza
vaccination
• Some studies support the association of pneumococcal pneumonia & the development of concurrent acute
cardiac events (eg MI, arrhythmia, new or worsening of CHF), hence they recommend pneumococcal vaccination
in high-risk populations
• Influenza & pneumococcal vaccinations are important in decreasing the risk of respiratory infection &
subsequent complications in patients w/ CVD during the COVID-19 pandemic
1Many lipid-lowering agents are available. Please see Dyslipidemia disease management chart for specific dosing recommendations.
B40
Dosage Guidelines
ANTICOAGULANTS, ANTIPLATELETS & FIBRINOLYTICS (THROMBOLYTICS)

Drug Dosage Remarks
Aspirin1 Prophylaxis of Adverse Reactions
CV events in • GI effects (dyspepsia, GI irritation, N/V); Hematologic effects
high-risk (increased bleeding time, decreased platelet adhesiveness,
patients hemorrhage); Hypersensitivity reactions
Short term: Special Instructions
150-300 mg PO • GI upset may be minimized by administering w/ food & w/ use of
24 hrly enteric-coated formulation
Long term:
CVD PREVENTION
• Contraindicated in patients w/ active pathological bleeding (eg peptic
75-150 mg PO ulcer, intracranial hemorrhage), known allergy, hemophilia,
24 hrly hemorrhagic disorders, severe renal or hepatic impairment
• Use w/ caution in patients w/ GI mucosa lesions, allergic disorders,
anemia, uncontrolled hypertension, G6PD deficiency
• Ensure that benefit outweighs the risk prior to use in combination w/
Warfarin, Heparin, thrombolytics, NSAIDs & other drugs that
increase the risk of bleeding
Clopidogrel1 75 mg PO Adverse Reactions
24 hrly • Hematologic effects (hemorrhage, purpura, epistaxis; blood
dyscrasias, including neutropenia, thrombotic thrombocytopenic
purpura have occurred); Dermatologic effects (rash, pruritus); GI
effects (abdominal pain, N/V, dyspepsia, constipation)
• Contraindicated in patients w/ active bleeding or severe liver
impairment
• Concurrent use of drugs known to inhibit CYP2C19 (eg Omeprazole,
Esomeprazole, Cimetidine, Fluconazole, Ketoconazole, Voriconazole,
Etravirine, Felbamate, Fluoxetine, Fluvoxamine & Ticlopidine) should
be avoided
- Separating the time of administration between the drugs does not
reduce the chance of interaction
• If possible, discontinue use 5-7 days prior to elective surgery
Prasugrel Initial dose: Adverse Reactions
60 mg PO • GI effects (N/V, diarrhea); Dermatologic effect (rash); Hepatic effects
24 hrly (elevated LFT, rarely hepatitis & cholestatic jaundice); Hematologic
Maintenance effects (neutropenia, thrombotic thrombocytopenic purpura,
dose: 10 mg PO agranulocytosis, hemorrhage)
24 hrly Special Instructions
• Contraindicated in patients w/ active bleeding, hemorrhagic diatheses,
In patients ≥75 patients w/ history of leukopenia, thrombocytopenia or
yr or w/ <60 kg agranulocytosis, history of stroke or TIA, severe hepatic impairment
body wt, reduce • Use w/ caution in patients w/ propensity to bleed, low body wt, or
maintenance who will undergo CABG & other surgical procedure
dose to 5 mg PO • Use w/ caution when combining w/ Warfarin, Heparin, thrombolytics,
24 hrly NSAIDs & other drugs that increase the risk of bleeding
1Combination products w/ Rosuvastatin are available.

B41
Dosage Guidelines
ANTICOAGULANTS, ANTIPLATELETS & FIBRINOLYTICS (THROMBOLYTICS) (CONT’D)

Drug Dosage Remarks
Ticagrelor Loading Adverse Reactions
dose: 180 mg • Hematologic effect (bleeding); Resp effect (dyspnea); CNS effects
PO 24 hrly (headache, dizziness); ENT effects (epistaxis, vertigo); GI effects
Maintenance (abdominal pain, N/V, constipation, diarrhea); Metabolic effect
dose: 90 mg (hyperuricemia); Dermatologic effects (rash, pruritus); Other effect
PO 12 hrly (post-procedural hemorrhage)
• Contraindicated in patients w/ active pathological bleeding, intracranial
CVD PREVENTION
hemorrhage history, known allergy, or severe hepatic impairment

• Use w/ caution in patients w/ increased risk for bradycardia
Warfarin Initial dose: Adverse Reactions
2-5 mg PO • Hemorrhage can occur even within therapeutic international normalized
24 hrly ratio (INR) levels
Lower • Other less common effects: Cholesterol embolization (skin necrosis &
initiation dose purple discoloration of the toes); GI effects (N/V, diarrhea, hepatic
in patients w/ dysfunction, pancreatitis); Other effects (alopecia, fever, skin reactions)
genetic Special Instructions
variation in • Dosage adjustments must be guided by regular monitoring of INR
CYP2C9 &
VKORC1 • Patients should be counseled on the risks of therapy along w/ drug & food
interactions
Maintenance
dose: • Avoid in patients w/ hemorrhagic states, bleeding from gastrointestinal
tract, genitourinary tract or resp tract, in patients w/ severe wounds,
2-10 mg PO infective endocarditis, impaired hepatic or renal function, w/
24 hrly hypertension, cerebrovascular hemorrhage, cerebral or aortic aneurysms,
Lower pericarditis, pericardial effusion, polyarthritis, threatened abortion
maintenance • Use w/ caution in patients w/ vitamin K deficiency, hyperthyroidism,
dose in polycythemia vera, vasculitis & severe diabetes
patients w/ a
potential to
have greater
than expected
PT/INR

B42
Dosage Guidelines
ANTIDIABETIC AGENTS
Drug Dosage Remarks
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists
Dulaglutide Initial dose: 0.75 mg SC Adverse Reactions
once wkly • GI effects (N/V, diarrhea, dyspepsia, gastroesophageal
May increase to 1.5 mg SC reflux, acute pancreatitis); CNS effects (dizziness,
once wkly headache); Other effects (rash, hypersensitivity reactions)
Max dose: 4.5 mg/wk • Uncommon effects include renal impairment & acute
Liraglutide Initial dose: 0.6 mg SC renal failure
CVD PREVENTION
May increase dose to • Avoid use in patients w/ type 1 DM or DKA, multiple
1.2 mg after at least 1 wk endocrine neoplasia syndrome type 2, personal or family
Max dose: 1.8 mg/day history of medullary thyroid carcinoma
• Discontinue use if acute pancreatitis occurs
Semaglutide Initial dose: 0.25 mg SC • Contraindicated in patients w/ hypersensitivity to the
once wkly for 4 wk then active substance or to any of the excipients
increase to 0.5 mg SC once
wkly for at least 4 wk
Max dose: 1 mg SC/wk
Sodium-Glucose Linked Transporter/Co-transporter 2 (SGLT2) Inhibitors
Canagliflozin 100 mg PO 24 hrly before Adverse Reactions
breakfast • GU effects (polyuria, dysuria, vulvovaginitis, balanitis,
Max dose: 300 mg/day increased susceptibility to infections); Renal effect (acute
kidney injury); Hematologic effect (increased hematocrit); GI
effects (nausea, constipation); CV effects (hypotension,
Dapagliflozin1 10 mg PO 24 hrly decreased blood volume); Other effects (dyslipidemia,
increased creatinine & urea levels, hypoglycemia, rash,
hyperhidrosis, back pain, euglycemic diabetic ketoacidosis)
• Electrolyte disturbances (hyperphosphatemia,
hypermagnesemia, hyperkalemia)
Empagliflozin1 10 mg PO 24 hrly Special Instructions
Max dose: 25 mg/day • Monitor kidney function prior to starting therapy &
assess periodically during therapy
• Use w/ caution in patients taking diuretics, NSAIDs & those
w/ decreased blood volume & congestive heart failure
• May need to lower doses of Insulin, sulfonylurea, insulin
secretagogues when used concomitantly w/ SGLT2 inhibitors
• Should not be given in patients w/ severe renal impairment
- Canagliflozin can be started in patients w/ eGFR 45 to
<60 mL/min/1.73 m2
- Dapagliflozin & Empagliflozin treatment can be
initiated in patients w/ eGFR ≥60 mL/min/1.73 m²
- Discontinue use if eGFR <45 mL/min/1.73 m2 is persistent
• Though current evidence suggests that CV & renal
benefits appear to be maintained even at eGFR levels as
low as 30 mL/min/1.73 m², physicians need to recognize
that at a level of CKD stage 3b & lower, the
glucose-lowering efficacy of SGLT2 inhibitors is weak
• Consider withholding SGLT2 inhibitors in events that may
precipitate diabetic ketoacidosis, eg intercurrent illness,
surgery (elective or emergency), trauma, severe
carbohydrate restriction
• SGLT2 inhibitors are generally safe for diabetic patients
during Ramadan but should be discontinued in select
patients whose risk for adverse effects might be increased
1Combination product w/ Metformin is available.

B43
Dosage Guidelines
DYSLIPIDAEMIC AGENTS
Drug Dosage Remarks
Other Lipid Modifying Agents
Alirocumab 75 mg SC every 2 wk or Adverse Reactions
300 mg SC every 4 wk • Resp effects (upper resp tract infection, nasopharyngitis,
Max dose: 150 mg SC cough); GI effects (gastroenteritis, diarrhea); Other effects
every 2 wk (influenza, back pain, inj site reactions, UTI, sinusitis,
Evolocumab 140 mg SC every 2 wk or myalgia, allergic reactions)
420 mg SC once mthly Special Instructions
CVD PREVENTION
• If serious signs & symptoms of allergic reactions occur,

discontinue therapy
• Measure LDL-C levels 4-8 wk after initiation or titration of
treatment
Ezetimibe1 10 mg PO 24 hrly Adverse Reactions
• Monotherapy: Diarrhea, abdominal pain, flatulence, fatigue
• When administered w/ a statin: Increased ALT &/or AST,
headache, myalgia
• When administered w/ a fenofibrate: Abdominal pain
• Use w/ caution in patients w/ renal & hepatic impairment
• Perform LFTs at initiation of therapy w/ a statin
Icosapent 2 g PO 12 hrly Adverse Reactions
ethyl • CV effects (peripheral edema, atrial fibrillation, atrial flutter);
GI effects (constipation, abdominal distress); Musculoskeletal
effects (arthralgia, musculoskeletal pain, limb pain): Other
effects (hemorrhage, gout, oropharyngeal pain, increased
serum TG)
• Must be taken w/ meals
• Use w/ caution in patients w/ coagulopathy, known allergy or
sensitivity to fish or shellfish
Lomitapide Initial dose: 5 mg PO 24 Adverse Reactions
hrly • GI effects (diarrhea, N/V, dyspepsia, abdominal pain,
May increase to 10 mg PO hepatotoxicity); Other effects (chest pain, decreased wt,
24 hrly after ≥2 wk of infections)
initiation, then additional Special Instructions
20 mg at 4-wk interval up • Contraindicated in patients taking CYP3A4 inhibitors & w/
to 60 mg based on safety moderate-severe hepatic impairment or active liver disease
& tolerability
• May reduce absorption of fat-soluble vitamins & serum fatty
Max dose: 60 mg PO acids
24 hrly
• Take at least 2 hr after evening meal
Mipomersen 200 mg SC once weekly Adverse Reactions
sodium • Inj site reactions (erythema, pain, tenderness, pruritus, local
swelling); Other effects (influenza-like illness, pyrexia, chills,
myalgia, arthralgia, malaise, fatigue, headache)
• Contraindicated in patients w/ moderate-severe hepatic
impairment or active liver disease
1Combination product w/ Atorvastatin or Simvastatin is available.

B44
Dosage Guidelines
DYSLIPIDAEMIC AGENTS (CONT’D)

Drug Dosage Remarks
Statins
Atorvastatin1 Individualize dose Adverse Reactions
according to baseline • Musculoskeletal effects (myalgia, arthralgia, muscle cramps); GI
LDL-C levels, goal of effects (nausea, abdominal pain, constipation); Other effects
therapy, & patient (rash, headache, dizziness)
response • Myopathy has occurred & is usually associated w/ high dose,
10-80 mg PO 24 hrly when statin is combined w/ Nicotinic acid or fibrate, in patients
CVD PREVENTION
Fluvastatin Regular-release: w/ renal or hepatic impairment, serious infections,
40 mg PO 12 hrly or hypothyroidism & advanced age
80 mg PO 24 hrly in - Rarely has rhabdomyolysis occurred
the evening - Advise patient to consult physician immediately if signs of
Extended-release: muscle pain suggesting myopathy occur (especially if
80 mg PO 24 hrly accompanied by fever & malaise)
Pravastatin 10-40 mg PO 24 hrly Special Instructions
in the evening • Dose should be based upon the individual’s lipoprotein profile &
Adjust dose according adjusted based on concomitant medications
to patient response at • Increases in dose should be done at ≥4-wk intervals based upon
4-wk intervals patient’s response until desired lipoprotein level is reached
Max dose: 80 mg PO • Should not be used in patients w/ active liver disease & in those
24 hrly w/ unexplained transaminase elevations
Rosuvastatin2 Individualize dose • Use w/ caution in patients w/ renal impairment as the risk of
according to goal of myopathy is increased
therapy, & patient • Liver function should be tested before or after 6-12 wk of
response therapy & w/ any dose increase
5-20 mg PO 24 hrly • Simvastatin: Due to increased risk of myopathy, including
rhabdomyolysis, use of 80 mg dose of Simvastatin should be
Simvastatin3 20-40 mg PO 24 hrly restricted to patients who have been taking this dose chronically
Max dose: 80 mg/day (≥12 mth) without evidence of muscle toxicity
1Combination products w/ Amlodipine or Ezetimibe are available.
2Combination products w/ Aspirin or Clopidogrel are available.
3Combination product w/ Ezetimibe is available.
SUPPLEMENTS & ADJUVANT THERAPY

Drug Dosage Remarks
Omega-3 1-4 g/day PO in 2 Adverse Reactions
fish oils divided doses (of a • GI effects (reflux, fish odor or taste, N/V, diarrhea, constipation);
(can be a preparation rarely eczema & acne
combination containing EPA & • Moderate elevation of transaminases have been reported in
of linolenic DHA) patients w/ hypertriglyceridemia
acid, DHA,
EPA) Special Instructions
• Due to moderate increase in bleeding time (w/ high dosage),
patients on anticoagulant therapy must be monitored & dosage of
anticoagulant adjusted as necessary

B45
Chronic Coronary Syndromes (1 of 32)
1
Patient presents w/ chest pain
UNSTABLE
2 2 ANGINA
EVALUATION EVALUATION See Acute Coronary
Do history & physical exam No Yes Syndromes w/out
Did evaluation Persistent ST-Segment
suggest chronic coronary reveal unstable
syndromes? Elevation disease
angina? management
chart
Yes No
4
2 ALTERNATIVE
EVALUATION DIAGNOSIS
What is the patient’s
clinical pre-test
probability
(PTP)?
Low PTP Intermediate-High PTP High PTP
3 CHRONIC
3 DIAGNOSIS CORONARY
Stress testing for ischemia SYNDROMES
DIAGNOSIS
• Exercise ECG
Did evaluation reveal
cardiac cause of • Stress imaging
chest pain? - Echocardiography*
- Cardiac magnetic resonance (CMR)
- Single photon emission computed
tomography (SPECT)
No Yes - Positron emission tomography (PET) Continue to
Anatomical evaluation next page
• Coronary computed tomography
4 angiography (CCTA)
ALTERNATIVE
DIAGNOSIS
RECONSIDER ISCHEMIC HEART DISEASE Continue to

(IHD) & START PRIMARY PREVENTION next page
Please see Cardiovascular Disease Prevention
disease management chart for further information
*Exercise or pharmacological stress (eg Dobutamine) echocardiography
B46
PATIENT W/ INTERMEDIATE-HIGH PTP
3 4
DIAGNOSIS ALTERNATIVE
Is chronic coronary No DIAGNOSIS
syndrome • Consider
confirmed? further testing
Yes
TREATMENT OF PATIENTS W/
CHRONIC CORONARY SYNDROMES
For
For angina
prevention of
relief
cardiac events
E Pharmacological therapy - Reduction A Patient education
CCS
of ischemia & relief of symptoms B Lifestyle modification
• Preferred agent: Beta-blockers
• Calcium channel blockers C Pharmacological therapy - Risk factor
• Long-acting nitrates modification
(for angina prophylaxis) • Dyslipidemia
• Short-acting nitrates • Hypertension
• Diabetes mellitus (DM)
(for acute-effort angina)
D Pharmacological therapy - Reduction
of incidence of adverse cardiac events
Antiplatelet agents
• 1st-line: Aspirin
• 2nd-line: Clopidogrel
Lipid-lowering agents
• Statins
Continue to Angiotensin-Converting Enzyme (ACE)
next page Inhibitors OR
Angiotensin Receptor Blockers (ARBs)
B47
TREATMENT OF PATIENTS W/ CHRONIC

CORONARY SYNDROMES (CONT’D)
H
FOLLOW-UP Yes
CONTINUE
Adequate TREATMENT
response?
No
OR patient has H Follow-up &
contraindication monitoring
to beta-blocker
E Add or substitute to beta-blocker:

• Calcium channel blocker (eg Dihydropyridines)*
• Long-acting nitrate
F Pharmacological therapy - Patients
unresponsive to initial therapy
• If channel inhibitor (eg Ivabradine)
• K channel activator (eg Nicorandil)
• Na channel inhibitor (eg Ranolazine)
• 3-Ketoacyl-CoA thiolase (3-KAT) inhibitor
(eg Trimetazidine)
CCS
PERFORM H
INVASIVE No Yes
CONTINUE
CORONARY Adequate TREATMENT
response?
ANGIOGRAPHY
G Revascularization
Suitable for Yes • Percutaneous coronary intervention (PCI)
revascularization?
• Coronary artery bypass grafting (CABG)
No
REVIEW OPTIMAL H Follow-up &

MEDICAL THERAPY monitoring
*Nondihydropyridines (eg Verapamil, Diltiazem) may be substituted to beta-blocker but not added due to risk of AV block or bradycardia.
B48
1 CHRONIC CORONARY SYNDROMES (CCS)

• Also known as stable coronary artery disease (CAD), stable ischemic heart disease (SIHD), chronic stable
angina or stable angina pectoris
• Clinical syndrome characterized by constricting discomfort in the chest, neck, jaw, shoulder, back or arms
which is precipitated by exertion &/or emotional stress & relieved by rest &/or Nitroglycerin
• Can be attributed to myocardial ischemia of which atherosclerotic CAD is the most common cause
- Obstructive CAD has ≥50% stenosis while nonobstructive CAD has <50% stenosis
• Angina is stable when it is not a new symptom & when there is no deterioration in frequency, duration or
severity of episodes
2 EVALUATION
• A good history & clinical examination is the key first step in the evaluation of a patient w/ chest pain
History
• Thorough history is the cornerstone of the diagnosis of angina pectoris
• Stable CAD may also present as dyspnea & palpitations; occasionally, patients w/ CAD may also present w/
syncope & near syncope
• In many cases, it is possible to make a diagnosis based on the history of chest pain alone but physical exam &
diagnostic tests are necessary to confirm the diagnosis, determine the cause & assess the severity of the underlying
disease
Signs & Symptoms
• Quality of chest pain
- Described as squeezing, grip-like, suffocating & heavy pain but rarely sharp or stabbing & typically does not
vary w/ position or respiration
- Occasionally, the patient may demonstrate a Levine’s sign in which a clenched fist is placed over the precordium
to describe the pain
- Many patients do not describe angina as frank pain but as tightness, pressure or discomfort
- Other patients, particularly women & elderly, can manifest w/ atypical symptoms such as nausea, vomiting,
midepigastric discomfort or sharp (atypical) chest pain
• Location of pain or discomfort
CCS
- Usually substernal & pain can radiate to the neck, jaw, epigastrium, shoulders, back or arms
- Pain above the mandible, localized to a small area over the left lateral chest wall or below the epigastrium is
rarely anginal
• Duration of pain
- Lasts for minutes, usually not >20 minutes
• Precipitating factors
- Often precipitated by exertion, emotional stress, heavy meal or cold weather
• Alleviating factors
- Typically relieved by rest
- Sublingual Nitroglycerin also relieves angina within 30 seconds to several minutes
Clinical Classification of Chest Pain
• Typical angina (definite or stable)
- Has substernal chest discomfort w/ a characteristic quality & duration provoked by exertion &/or emotional
stress & relieved by rest &/or Nitroglycerin within minutes
• Atypical angina (probable) has two of the characteristics of typical angina
• Noncardiac/anginal chest pain only has one or none of the characteristics of typical angina
Physical Examination
• It is usually normal or nonspecific in stable angina patients
• Exam during or immediately after an episode of pain may be beneficial since S4 or S3 heart sound or gallop,
mitral regurgitation murmur, paradoxically split S2, basilar rales or chest wall heave that dissipates when pain
decreases are all predictive of ischemic heart disease (IHD)
• Careful cardiovascular (CV) exam may reveal other related conditions such as heart failure, valvular heart
disease or hypertrophic cardiomyopathy
• Audible rub suggests pericardial or pleural disease
• Presence of carotid bruit, renal artery bruit, diminished pedal pulse or palpable abdominal aneurysm are
evidences of vascular disease
• Elevated blood pressure (BP), xanthomas & retinal exudates are signs which suggest the presence of IHD risk factors
• Chest pain elicited by pressure on the chest wall can be caused by musculoskeletal syndromes but does not
eliminate the possibility of angina due to IHD
• Body mass index (BMI), waist circumference & waist-to-hip ratio should also be taken to determine possible
metabolic syndrome, non-coronary vascular disease & other signs of comorbid conditions
B49
2 EVALUATION (CONT’D)
Classification of Angina Severity
• Helps determine the functional impairment, response to therapy & prognosis of the patient
- Eg Canadian Cardiovascular Society Classification, Duke Specific Activity Index & Seattle Angina
Questionnaire
CANADIAN CARDIOVASCULAR SOCIETY ANGINA CLASSIFICATION

Class Level of Symptoms
Class I • Ordinary activity does not cause angina
• Angina due to strenuous, rapid or prolonged exertion only
Class II • Moderate exertion causes angina
• Slight limitation of ordinary activity when done rapidly, after meals, walking uphill, under
emotional stress, in cold or windy weather or during the first few hours after waking up
• Angina when walking >2 blocks on the same level & climbing >1 flight of stairs at a
normal pace under normal conditions
Class III • Marked limitation of ordinary physical activity
• Angina when walking 1 or 2 blocks on the same level or 1 flight of stairs at a normal pace
under normal conditions
Class IV • Unable to carry out any physical activity without discomfort or angina may be present at rest
Reference: Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary
syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of
Cardiology (ESC). Eur Heart J. 2019;1-71.
Categories of Chronic Coronary Syndromes

• Based on the different presentations of patients w/ suspected or established CCS by the European Society of
Cardiology (ESC)
- Category 1: Patients w/ suspected CAD & “stable” anginal symptoms; angina may present as dyspnea
- Category 2: Patients w/ new onset of heart failure or left ventricular dysfunction & suspected CAD
- Category 3: Asymptomatic & symptomatic patients <1 year after an acute coronary syndrome or recent
CCS
revascularization
- Category 4: Patients >1 year after being diagnosed w/ angina or >1 year after revascularization
- Category 5: Patients w/ angina & suspected vasospastic or microvascular disease
- Category 6: Asymptomatic patients in whom CAD is detected at screening
• Presence of these scenarios may increase or decrease patient’s risk for future CV events
- Insufficiently controlled CV risk factors, ineffective lifestyle modifications &/or medical therapy, or
unsuccessful revascularization may increase the risk for CV events
- Appropriate secondary prevention & successful revascularization have been shown to reduce risk for major
CV events
Conditions that Exacerbate or Provoke Ischemia
Noncardiac Diseases
• Hyperthyroidism
• Hyperthermia
• Anxiety
• Anemia
• Hyperviscosity
• Leukemia
• Hypertension
• Sympathomimetic toxicity (eg cocaine toxicity)
• Arteriovenous fistulae
• Sickle cell disease
• Polycythemia
• Thrombocytosis
• Hypergammaglobulinemia
• Hypoxemia secondary to pneumonia, asthma, chronic obstructive pulmonary disease, pulmonary hypertension,
obstructive sleep apnea, interstitial pulmonary fibrosis
B50
Conditions that Exacerbate or Provoke Ischemia (Cont’d)
Cardiac Diseases
• Arrhythmias (eg supraventricular tachycardia, ventricular tachycardia)
• Aortic stenosis
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Significant coronary obstruction
• Microvascular disease
Rule Out Unstable Angina
• Unstable angina is defined as angina of new onset, increases in frequency, intensity or duration, or occurs at
rest
• Presence of unstable angina predicts a higher short-term risk of acute coronary event
• Moderate- to high-risk patients should be promptly evaluated & treated in the emergency department because
of higher risk of coronary artery plaque rupture & death
• Low-risk patients are comparable to those patients w/ stable angina & their evaluation can be performed safely
& expeditiously in an outpatient setting
• Please see Acute Coronary Syndromes w/out Persistent ST-Segment Elevation disease management chart for
further information
Assess for IHD Risk Factors
• Presence of IHD risk factors should be assessed
- Eg smoking, dyslipidemia (eg familial hypercholesterolemia), DM, hypertension, obesity, metabolic syndrome,
physical inactivity & family history of premature CV disease
• History of cerebrovascular disease, peripheral artery disease (PAD), myocardial infarction (MI) or coronary
revascularization also increases the likelihood of IHD
Risk Stratification
• Risk refers to the risk of CV event (eg death)
- Low risk has an annual mortality of <1%, intermediate risk 1-3% & high risk >3%
• Uses clinical findings, resting ECG, response to stress testing, quantification of left ventricular function &
CCS
extent of CAD to determine the level of risk
• Assists in deciding the appropriate therapy & determines prognosis of the disease
- Low-risk patients are managed w/ risk factor reduction w/ or without anti-anginal therapy while intermediate
to high-risk patients are referred to specialists for further evaluation & possible revascularization
Clinical Pre-test Probabilities (PTP)
• Clinician’s pre-test estimates of disease along w/ the results of diagnostic tests to generate individualized post-
test disease probabilities for a given patient
• Influenced by the prevalence of the disease in the population studied, as well as clinical features including the
presence of CV risk factors of an individual
• Major determinants are age, gender & the nature of symptoms
- Likelihood of CAD is increased w/ the following: Presence of risk factors for CVD (eg smoking, hypertension,
DM, dyslipidemia, family history of CVD), Q-wave or ST-segment/T-wave changes from a resting ECG, LV
dysfunction suggestive of CAD, abnormal exercise ECG & presence of coronary calcium by CT
• According to the 2013 ESC guidelines, PTP of CAD are as follows:
- Low PTP <15%: Patients can be managed without further non-invasive stress testing but it is recommended
to exclude other causes of chest pain (eg pulmonary, gastrointestinal, musculoskeletal)
- Intermediate PTP ≥15-≤85%: An exercise ECG may be considered in patients w/ 15-65% PTP while a
non-invasive imaging is preferred in those w/ 66-85% PTP
- High PTP >85%: Patients can be assumed to have stable CAD & an invasive coronary angiography (ICA)
may be considered for risk stratification
B51
3 DIAGNOSIS
Diagnostic Tests
Laboratory Tests
• Provide information related to the possible causes of ischemia, establish cardiovascular risk factors & determine
prognosis
• Fasting lipid profile
- To determine the presence of dyslipidemia, establish the patient’s risk profile & help determine the need for
treatment
• Fasting blood glucose & glycated hemoglobin (HbA1c)
- To identify undiagnosed DM & establish patient’s risk profile
- An oral glucose tolerance test is recommended if both tests are inconclusive
• Complete blood count (CBC) that includes hemoglobin & white cell count
- To check underlying anemia &/or infection
- For prognostic information
• Serum creatinine
- To assess renal function
• Cardiac enzymes (troponins, creatine kinase)
- To rule out myocardial injury/necrosis
- Creatine kinase measurement may be decreased for patients on statin therapy w/ accompanying symptoms
of cardiac injury
• Liver function tests
- Recommended prior to initiation of statin therapy
• Thyroid function test
- To identify other causes of ischemia
Chest X-ray
• Commonly used to evaluate patients w/ suspected heart disease but does not provide the exact diagnosis nor
classify risk group
• Recommended for patients w/ signs & symptoms of heart failure, atypical presentation or suspicion of pulmonary
disease
CCS
• Presence of cardiomegaly, pulmonary congestion, atrial enlargement & cardiac calcifications have been related
to poor outcome
If patient has low probability of IHD, then appropriate diagnostic tests should focus on noncardiac causes
of chest pain
Non-invasive Cardiac Investigations
• Used in the assessment of angina, in diagnosis, evaluation of treatment efficacy & risk stratification
• Imaging tests are recommended for patients w/ PTP of 65-85%, ejection fraction of >50% without typical
angina or ECG abnormalities
• The choice for the initial non-invasive test should be based on the PTP, availability of the test, the test’s performance
in diagnosing obstructive CAD, patient characteristics & local expertise
Resting ECG
• Recommended in all patients w/ suspected angina pectoris
• Should be done during or immediately after an episode of chest pain to detect ST-segment changes in the
presence of ischemia
• Also used in patients without an obvious noncardiac cause of chest pain
• Normal resting ECG is common even in patients w/ severe angina which does not exclude the possibility of
ischemia
• Assists in clarifying the differential diagnosis if taken in the presence of pain which can detect dynamic
ST-segment changes in the presence of ischemia or by identifying features of pericardial disease
• ECG during an episode of chest pain is useful if vasospasm is suspected
• ECG abnormalities indicating a worse prognosis:
- Evidence of prior MI, especially Q waves in multiple leads or an R wave in V1
- Persistent ST-T wave inversions, particularly in leads V1 to V3
- Left bundle branch block (LBBB), left anterior hemiblock, bifascicular block, second- or third-degree
atrioventricular (AV) block or ventricular tachyarrhythmia/atrial fibrillation
- Left ventricular hypertrophy
B52
Non-invasive Cardiac Investigations (Cont’d)
Resting Echocardiography
• Recommended in the initial evaluation of all patients w/ symptoms suggestive of SIHD
• Resting 2-dimensional & Doppler echocardiography are useful to evaluate ventricular function & regional wall motion
abnormalities & detect or rule out other CV disorders (eg valvular heart disease, hypertrophic cardiomyopathy)
• Estimation of left ventricular ejection fraction (LVEF) & left ventricular diastolic function which are very
important in risk stratification
• Not indicated for repeated use on a regular basis in patients w/ uncomplicated stable angina in the absence or
change in clinical condition
• Carotid artery ultrasonography may be done to look for presence of plaque or narrowing
Exercise ECG or ECG Stress Test
• Commonly used diagnostic test for IHD
• Evaluates exercise tolerance, symptoms, BP response, arrhythmias & event risk in some patients
• Preferred test to determine inducible ischemia for patients w/ suspected stable angina, PTP of 15-60% & LVEF ≥50%
• Alternative test to diagnose CAD when other invasive or non-invasive imaging tests are unavailable
• Only for diagnostic confirmation in patients w/ an intermediate PTP of IHD who have an interpretable ECG
& at least moderate physical functioning or no disabling comorbidity
- Should only be done on high-risk populations for determination of prognosis [ie, a high event risk in a patient
w/ established CCS is a CV mortality of >3% per year based on the Duke Treadmill Score]
• Should be done only after clinical examination & resting ECG under careful monitoring
• Complications during exercise testing are few but severe arrhythmia & sudden death may occur
• Absolute contraindications to exercise ECG are:
- MI within the last 2 days, cardiac arrhythmias causing symptoms or hemodynamic compromise, symptomatic
& severe aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure, pulmonary embolism,
pulmonary infarction, myocarditis, pericarditis & acute aortic dissection
• More sensitive & specific than resting ECG for detecting myocardial ischemia
• Test should be standardized using nomograms taking into account age, gender & body size
• No diagnostic value in patients w/ LBBB, paced rhythm & Wolff-Parkinson-White (WPW) syndrome
CCS
• Normal test in patients taking anti-ischemic drugs does not rule out significant coronary disease
- Withhold beta-blockers for 24-48 hours prior to testing to prevent false-negative findings
• In patients unable to perform adequate amount of treadmill or bicycle exercise, various types of pharmacological
stress tests can be useful (eg Adenosine, Dipyridamole)
- Selection & type of pharmacological stress will depend on individual patient factors
• Treatment can be initiated without stress test if patient has high probability of CAD but the test is contraindicated
because of comorbidity or patient preference
• Can be useful for prognostic stratification, to assess the efficacy of medical therapy or revascularization or to
assist prescription of exercise after control of symptoms
- Prognostic value is increased by considering heart rate variability, predicted maximum heart rate & heart
rate recovery index
Stress Testing in Combination w/ Imaging
• Most well-established stress imaging modalities that may be used w/ either exercise test or pharmacological
stress tests are:
- Stress echocardiography
- Myocardial perfusion scintigraphy (SPECT, PET)
- Stress CMR
- Others (hybrid SPECT & CT, PET & CT, PET & CMR)
- Further studies are needed to prove the accuracy of hybrid techniques for CAD imaging
• Recommended for patients within the higher range of PTP or LVEF<50% without typical angina & in patients
w/ resting ECG abnormalities, especially symptomatic patients w/ previous PCI or CABG
- Also for patients w/ intermediate PTP w/ inadequate ability to exercise, uninterpretable resting ECG &/or
exercise stress ECG w/ equivocal or abnormal results at moderate to high workloads depending on patient’s
clinical condition
• May be performed after an inconclusive CCTA in intermediate- to high-risk patients w/ stable chest pain
• Helps in the diagnosis of myocardial ischemia, estimation of major adverse CV events (MACE) risk & guidance
of treatment decisions in patients w/ obstructive CAD
• Exercise imaging is preferable if possible because it allows more physiological reproduction of ischemia &
assessment of symptoms
B53
Stress Testing in Combination w/ Imaging (Cont’d)
• A high event risk in a patient w/ established CCS includes a finding of ≥3 of 16 segments w/ stress-induced
hypokinesia or akinesia on stress echocardiography & ≥10% ischemic area on the left ventricle myocardium
on SPECT or PET perfusion imaging
• Pharmacological stress testing is indicated in patients who are not able to exercise adequately or may be used
as an option to exercise stress tests
- Two approaches are used:
- Infusion of short-acting sympathomimetic drugs (eg Dobutamine) in an incremental dose which increases
myocardial oxygen consumption & mimics the effect of physical exercise
- Infusion of coronary vasodilators (eg Adenosine & Dipyridamole) which provide a contrast between regions
supplied by non-diseased coronary arteries where perfusion increases & regions supplied by significant
stenotic coronary arteries where perfusion will increase less or even decrease (steal phenomenon)
• Advantages of stress imaging over conventional exercise ECG testing:
- Superior diagnostic performance for detecting obstructive coronary disease
- Ability to quantify & localize ischemic areas
- Ability to provide diagnostic information if there are resting ECG abnormalities or the patients are unable
to exercise
- Ability to establish the functional significance of lesions in patients w/ confirmed lesions by ICA
- Ability to show myocardial viability
Computed Tomography (CT)
• Ultra-fast or electron beam CT & multi-detector or multi-slice CT are two modalities of CT imaging that
were developed to improve spatial & temporal resolution in CT
• Recommended in patients w/ a low PTP (15-50%) of disease & w/ intermediate to high PTP w/ non-conclusive
exercise ECG or stress imaging test
• Effective in detecting coronary calcium & quantifying the extent of coronary calcification
- Calcium is deposited in atherosclerotic plaques within the coronary arteries
- Coronary calcification increases w/ age
CCS
- Extent of coronary calcification correlates more closely w/ the overall burden of plaque than w/ the location
or severity of stenoses
• Detection of coronary calcium may identify those at higher risk of significant coronary disease, but assessment
of coronary calcification is not recommended routinely for the diagnostic evaluation of patients w/ stable
angina
Cardiac Magnetic Resonance (CMR)
• Used to define structural cardiac abnormalities & evaluate ventricular function
• In conjunction w/ Dobutamine or adenosine infusion, CMR stress testing can be used to detect wall motion
abnormalities or perfusion defect induced by ischemia
• A high event risk in a patient w/ established CCS includes a finding of ≥2 of 16 segments w/ stress perfusion
defects or ≥3 Dobutamine-induced dysfunctional segments
Ambulatory ECG (Holter) Monitoring
• A diagnostic monitoring option for patients suspected of having arrhythmia or vasospastic angina
Coronary Computed Tomography Angiography (CCTA)
• Radiographic visualization of the coronary vessels after injection of radiopaque contrast material
• Identifies the presence or absence of coronary lumen stenosis, stratifies patient’s risk, provides therapeutic
options (eg medical therapy or revascularization) & helps determine prognosis
• CCTA or a non-invasive functional imaging for myocardial ischemia may be used as an initial test to diagnose
CAD in symptomatic patients in whom clinical evaluation alone cannot rule out an obstructive CAD
• Extent & severity of angiographic CAD are the most important prognostic factors & essential for revascularization
decision making
• Has high sensitivity & specificity for detecting obstructive CAD
- Sensitive to heart rate, body weight & the presence of calcification
• A very high negative predictive value for obstructive CAD is an advantage of CCTA over standard functional
testing
- If CCTA demonstrated CAD of uncertain functional significance or is non-diagnostic, it is recommended
to perform functional imaging for myocardial ischemia
B54
Coronary Computed Tomography Angiography (CCTA) (Cont’d)
• May be considered in patients w/ low-intermediate risk PTP w/ exercise stress test or stress imaging tests showing
mild or equivocal ischemic changes & are asymptomatic or mildly symptomatic w/ good exercise capacity
- Should not be performed in patients who are at high risk for CAD or have extensive calcification because
the presence of significant calcification can preclude the accurate assessment of lesion severity or may result
to a false-positive study
- Not advisable for patients unwilling to undergo invasive procedures & revascularization, not candidates for
PCI, CABG & those w/ low probability of recovering even after revascularization
• Indications for coronary angiography:
- Severe stable angina w/ a high PTP of disease, particularly if the symptoms are inadequately responding to
medical therapy
- Survivors of cardiac arrest
- Serious ventricular arrhythmias
- Previously treated by myocardial revascularization (PCI, CABG) who developed early recurrence of moderate
or severe angina pectoris
- Inconclusive diagnosis on non-invasive testing or discordant test results from different non-invasive modalities
at intermediate to high risk of coronary level
- High risk of restenosis after PCI if PCI has been performed in a prognostically important site
Invasive Cardiac Investigation
Invasive Coronary Angiography (ICA)
• It is recommended to perform ICA as an alternative test in diagnosing CAD & for guidance during treatment
decisions in patients w/ a high clinical likelihood & moderate to severe symptoms unresponsive to medical
therapy, or typical angina w/ low-level exercise & clinical evaluation showing a high event risk
• ICA is recommended for the following:
- CV risk stratification of symptomatic patients w/ high-risk clinical profile w/ symptoms not responding
adequately to medical therapy & revascularization is considered to improve prognosis
- Patients w/ mild or no symptoms receiving medical therapy w/ a non-invasive risk stratification showing a
high event risk & revascularization is considered to improve prognosis
CCS
• Considered for confirmation of CAD diagnosis (together w/ invasive functional evaluation) when non-invasive
testing reveals uncertain diagnosis
• A high event risk in a patient w/ established CCS includes a finding of 3-vessel disease w/ proximal stenoses,
left main disease or proximal anterior descending disease (findings which may also be seen w/ CCTA)
4 ALTERNATIVE DIAGNOSIS
• Non-ischemic chest pain may also be caused by neuralgia, myalgia, costochondritis, psychosomatic disorder,
pericarditis, pleurisy, pneumothorax, pulmonary embolism, esophageal spasm, gastroesophageal reflux disease,
peptic ulcer disease, gallstone disease, pancreatitis
A PATIENT EDUCATION
• Effective education about CCS & IHD is important
- Educate patients about the etiology, manifestations, provoking factors, treatment options & prognosis of
CCS & IHD to encourage active participation of the patients in their treatment decisions
- Patients are more likely to participate in therapeutic & preventive measures if they have a full understanding
of the potential benefits
- Education about risks of CCS typically relieves patient’s anxieties & concerns
- Reasonable reassurance is essential & patients may also benefit from relaxation techniques & other ways of
stress control
• Education should be a part of every patient encounter & should be tailored to the patient’s level of understanding
• Individualize education plan to optimize care & promote wellness
- Develop a plan w/ the patient & hold discussions over time so that the patient is not overwhelmed by changing
several behaviors all at one time (eg smoking, diet, exercise, etc)
- Educate them on self-monitoring skills, recognition of worsening cardiovascular symptoms & appropriate
actions to take
- Inform them about the common symptoms of stress & depression to lessen stress-related angina symptoms
B55
A PATIENT EDUCATION (CONT’D)

• Discuss treatment goals & strategies to improve compliance
• Enlist family members into the educational process to assist the patient in achieving lifestyle modifications
Treatment Regimen
• Should be individualized
• Emphasize the importance of lifestyle modifications & medication adherence for managing symptoms &
retarding disease progression
• Explain medication management & cardiovascular risk reduction strategies
• Adherence to medication regimen is more likely to be followed by a patient who is adequately counseled about
their prescribed medications
- Poor compliance can lead to increased morbidity & mortality
• Review all therapeutic options including risk-benefit profile
Influenza Vaccination
• Annual influenza vaccination is recommended for patients w/ IHD especially the elderly
- Decreases exacerbation of underlying medical condition & risk for mortality in patients w/ chronic illnesses
such as CV disease
B LIFESTYLE MODIFICATION
• It is important to assess the presence of IHD risk factors & to treat these effectively
- Studies that involved risk modification, that includes weight control, exercise, healthy diet & smoking cessation,
have demonstrated benefits in patients w/ angina & coronary disease
Dietary Therapy1
• Goals:
- Reduce intake of saturated fats to <10% of total calories, trans fatty acids to <1% of total calories & cholesterol
to <200 mg/day by avoiding red meat, whole milk products & pastries
- Limit sodium intake to <5 g/day
- Eat fresh fruits (≥200 g/day), vegetables (≥200 g/day), legumes, nuts, soy products, low-fat dairy products
& whole grain breads, cereals & pastas
CCS
- Light to moderate alcohol consumption of 1 glass/day or 10 g/day for women & 2 glasses/day or 20 g/day of
alcohol for men (1 drink is equivalent to 4 ounces of wine, 12 ounces of beer or 1 ounce of spirits per day)
- Increase intake of polyunsaturated fat which is high in omega-3 fatty acids by eating oily fish, walnuts, sesame
seeds, pumpkin seeds, vegetable oils or taking omega-3 fatty acid supplements (1 g/day)
- Increase intake of soluble fiber 30-45 g/day
- Energy intake should be limited to the amount of energy needed to maintain or obtain a healthy weight (BMI
<25 kg/m2)
• Start all patients on dietary therapy & adopt a healthy eating habit
• Effective adjunct measure if properly implemented
• Has favorable effects on many CAD risk factors such as hypertension, hypercholesterolemia, obesity & DM
• The Prospective Urban Rural Epidemiology (PURE) study recently showed that high carbohydrate intake (>60%
of energy) was associated w/ an adverse effect on total & non-cardiovascular disease mortality whereas a high
fat intake (including saturated & unsaturated fatty acids) was associated w/ lower risk of total mortality,
non-cardiovascular disease mortality & stroke
- Limit overall carbohydrate intake especially from refined sources
• Recent studies have shown that a diet supplemented by extra-virgin olive oil or nuts reduce the incidence of
major cardiovascular events in patients at high risk of CV events but without prior CV disease
• Antioxidants & other vitamins are not recommended
- Vitamins B, C, E, beta-carotene, folate, coenzyme Q10, selenium & chromium are not recommended to
prevent cardiovascular risks or improve clinical outcome
Smoking Cessation
• Goals: Complete smoking cessation & avoidance of exposure to secondhand smoke
• Effective way for the prevention of coronary events
• Most important reversible risk factor
• Smoking status including passive smoking should be assessed systematically
B56
B LIFESTYLE MODIFICATION (CONT’D)

Smoking Cessation (Cont’d)
• Implement the algorithm for smoking cessation “Ask, Advice, Assess, Assist, Arrange, & Avoid”
- Ask the patient about tobacco use at every visit
- Advise the smoker to quit
- Assess the smoker’s willingness to make a quit attempt
- Assist the smoker by providing medications & referral for counseling
- Arrange for follow-up
- Avoid exposure to environmental tobacco smoke at home & at work
• Most effective smoking cessation therapies include both non-pharmacological & pharmacological therapies
- Physician’s advice has a significant effect on quit rates
- Self-help programs, telephone counseling, behavioral therapy & exercise programs have modest effects
- Nicotine-replacement therapy, Bupropion & Varenicline increase the chances of success of quit attempt
- However, there are concerns of possible increase in the risk of CVD, worsening of preexisting depression
& risk of suicide due to Varenicline based on few studies
• There are well-conducted epidemiological studies that clearly show cigarette smoking increases the risk for
CV events
- Dose-response relationship exists between cigarettes smoked & CV risks
Physical Activity
• Goals:
- Moderate-to-vigorous intensity aerobic exercise training ≥3 times a week & for 30 minutes per session is recommended
in patients w/ previous acute MI, CABG, PCI, stable angina pectoris or stable chronic heart failure
- Light-intensity exercise programs should be started in sedentary patients after adequate exercise-related risk
stratification
- Increase daily lifestyle activities (eg brisk walking, walking to work, household chores, gardening)
• Exercise improves cardiorespiratory fitness, functional capacity, & quality of life
• Exercise training when incorporated into a multifactorial risk factor reduction effort (eg smoking cessation,
lipid management, etc) has been shown to improve exercise tolerance in CCS patients
• Exercise training may offer an alternative means of symptom alleviation & improved prognosis in patients w/
significant CAD who are candidates for revascularization
CCS
- Complimentary resistance training for at least 2 days per week is reasonable
• Assess risk w/ a physical activity history &/or exercise test to guide prognosis & prescription of exercise program
- Exercise test is not necessary if the patient undergoes a low- or moderate-intensity level program
• Nitroglycerin may be used prior to sexual intercourse to help prevent ischemia
- Phosphodiesterase type 5 inhibitors may be given to patients w/ CAD w/ erectile dysfunction but should not
be given to patients on nitrates
• Exercise-based cardiac rehabilitation is an effective way of managing risk factors & achieving a healthy lifestyle
in CCS patients
• Reduces CV mortality & hospitalizations in patients w/ CAD
• Most patients referred for cardiac rehabilitation are those who had an acute MI or underwent revascularization
Weight Management
• Goals:
- Body mass index (BMI):
- Asian adults: 18.5-22.9 kg/m2
- American/European adults: 18.5-24.9 kg/m2
- Waist circumference:
- Asian: Male <35 in (90 cm), female <31.5 in (80 cm)
- American/European: Male <40 in (102 cm), female <35 in (88 cm)
• Initial weight loss goal is 5-10% from baseline w/ further reductions if necessary
• Measure BMI &/or waist circumference every clinic visit
• Risks for cardiovascular events are higher in overweight & obese patients
- Cardiovascular risk is particularly increased in central obesity & those w/ extreme obesity
- Obesity also contributes to other cardiovascular risk factors such as DM, dyslipidemia & hypertension
• Encourage weight maintenance or reduction through an appropriate balance of physical activity, structured
exercise, caloric intake & formal behavior programs
• Medications or bariatric surgery may be considered in selected patients who cannot achieve adequate weight
loss by lifestyle modifications
• Please see Obesity disease management chart for further information
B57
• In patients w/ stable chest pain, it is recommended to optimize guideline-directed medical therapy in those
w/ obstructive CAD & to optimize preventive therapies in those w/ nonobstructive CAD
Goals of Therapy
• Both anti-anginal therapy & treatment to reduce incidence of adverse cardiac events should be administered
• Individualize treatment based on patient’s expectations & preferences
• Relief of anginal symptoms & reduction of ischemia
• Improved chest pain-free exertion capacity
• Prevention of subsequent acute MI, unstable angina & cardiac death
C PHARMACOLOGICAL THERAPY - RISK FACTOR MODIFICATION

Treat Dyslipidemia
• Goals:
- Low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL (<1.4 mmol/L) & ≥50% LDL-C reduction from
baseline in very high-risk patients (patients w/ established ASCVD)
- For patients w/ ASCVD who had a 2nd vascular event within 2 years (not necessarily of the same type as
the 1st) while on maximally tolerated statin-based therapy, an even lower LDL-C target level of <40 mg/
dL (<1.0 mmol/L) may be considered
- High-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL (≥1.6 mmol/L) (negative risk factor)
- Triglyceride (TG) <150 mg/dL (<1.7 mmol/L)
• Assess fasting lipid profile in all patients & within 24 hours of hospitalization for those patients who present
w/ an acute event if not previously done
• Lifestyle modifications which include daily physical activity & weight management are strongly recommended
for all IHD patients
- Add plant stanol/sterols at 2 g/day &/or viscous fiber >10 g/day to further lower LDL-C
- Take higher doses of omega-3 fatty acid (2-4 g/day) for elevated TG
• High-dose statin therapy that results in ≥50% reduction in LDL-C levels is recommended in the absence of
contraindications or adverse effects in addition to lifestyle modifications
- Consider combination w/ Ezetimibe if target goals are not achieved w/ maximally tolerated dose of statin
- Consider combination w/ a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for very high-risk
CCS
patients who did not achieve target goals on maximally tolerated dose of statin & Ezetimibe combination therapy
• Bile acid sequestrants, Niacin or Ezetimibe are alternative agents for patients who cannot tolerate statins
• Therapy can be started soon after admission & continued on discharge if the patient has been hospitalized
• Patients w/ TG ≥500 mg/dL (≥13 mmol/L): Niacin or fibrate should be initiated before LDL-C-lowering therapy
Treat Hypertension
• Goal: BP <130/80 mmHg in patients w/ uncomplicated hypertension, DM & chronic renal disease*
• BP monitoring & lifestyle modification are recommended in all patients w/ IHD
• Antihypertensive therapy should be initiated in addition to or after a trial of lifestyle modifications
• Choice of antihypertensive drugs is based on patient characteristics, indications for specific classes of drugs
& comorbid illnesses
- It may include ACE inhibitors, angiotensin receptor blockers (ARBs) &/or beta-blockers, w/ addition of other
drugs such as thiazide diuretics or calcium channel blockers if necessary to achieve optimal BP control
- It is recommended to give beta-blockers & renin-angiotensin system blockers to post-MI hypertensive
patients & beta-blockers &/or calcium channel blockers to patients w/ symptomatic angina
- ACE inhibitors or ARBs should always be included because of the renal protective effects
Treat Diabetes
• Goal: Should be individualized; for most adults, recommended glycosylated hemoglobin (HbA1c) goal is <7%
• Diabetes management includes lifestyle modification & pharmacological therapy to achieve the target HbA1c
- For patients w/ DM & CVD, sodium-glucose linked transporter/co-transporter 2 inhibitors & glucagon-like
peptide-1 receptor agonists are recommended
• Treatment of other modifiable risk factors that accompany DM such as hypertension & dyslipidemia results
in a substantial decrease in cardiovascular risk
*Recommendations for BP goals may vary between countries. Please refer to available guidelines from local health authorities.
B58
D PHARMACOLOGICAL THERAPY - REDUCTION OF INCIDENCE

OF ADVERSE CARDIAC EVENTS
Antiplatelet Agents
Aspirin
• Antiplatelet drug of choice (cost effective)
• Aspirin should be given indefinitely in patients w/ IHD unless there are contraindications
• Exerts antithrombotic effect by irreversibly inhibiting prostaglandin synthetase action which prevents
production of platelet-aggregating substance thromboxane A2
• Has shown to be associated w/ a reduction in the risk of serious vascular events
• Aspirin 75-100 mg/day is recommended in patients in sinus rhythm w/ a prior MI or revascularization or after
stenting
• Aspirin dose of 75 to 162 mg/day is equally as effective as 325 mg/day in secondary prevention & is associated
w/ a lower risk of hemorrhage
• The addition of a second antithrombotic agent to Aspirin for long-term secondary prevention in patients
without high bleeding risk should be considered in those whose risk of ischemic events is high & may be
considered in those whose risk of ischemic events is at least moderately increased
• Use the lowest effective dose to optimize the balance between therapeutic benefits & gastrointestinal side effects
during chronic therapy
- A proton pump inhibitor may be used concomitantly if risk of gastrointestinal bleeding is high
Clopidogrel
• Used as an alternative drug if Aspirin is contraindicated or if patient experiences serious adverse effects from
Aspirin
• Inhibits platelet aggregation via selective & irreversible inhibition of adenosine diphosphate receptor
• In addition to Aspirin, Clopidogrel (after appropriate loading dose) may be given for 6 months after coronary
stenting to patients in sinus rhythm, unless the risk or occurrence of life-threatening bleeding warrants a
shorter course (1-3 months)
• A study showed that Clopidogrel demonstrated superiority over Aspirin in the secondary prevention of MI &
death in patients w/ previous MI, stroke or symptomatic PAD
- However, the difference was small & no other trials have been conducted in patients w/ SIHD
CCS
- Thus, Clopidogrel remains to be an acceptable alternative drug to Aspirin
Lipid-lowering Agents
• Have shown that a decrease in LDL-C is associated w/ reduced risk of adverse cardiovascular events
• Studies showed decrease in chest pain & need for revascularization in patients w/ stable CAD
Statins
• Eg Atorvastatin, Rosuvastatin, Simvastatin
• Recommended in all patients w/ CCS
• Effective in the primary & secondary prevention of coronary events & lipid management
• Other agents which may be added to statins to achieve LDL-C targets include Ezetimibe, PCSK9 inhibitors &
Inclisiran
Angiotensin-Converting Enzyme (ACE) Inhibitors
• Recommended in all patients w/ SIHD who also have hypertension, DM, left ventricular ejection fraction
(LVEF) of ≤40% [symptomatic heart failure (HF) or asymptomatic LV dysfunction after MI] or chronic renal
disease unless contraindicated or patients at very high risk of CV adverse events
• Reduce angiotensin II w/ an increase in bradykinin which decrease left ventricular & vascular hypertrophy,
atherosclerosis progression, plaque rupture & thrombosis
• Aldosterone blockade w/ Spironolactone or Eplerenone is recommended for use in post-MI patients without
significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor
& a beta-blocker, have an LVEF ≤35% & have either diabetes or heart failure
- May also consider giving an angiotensin receptor-neprilysin inhibitor (as a replacement to an ACE inhibitor)
to patients w/ an LVEF ≤35% who are still symptomatic despite optimal therapy w/ an ACE inhibitor, a
beta-blocker & a mineralocorticoid receptor antagonist (MRA)
• Exhibit cardiovascular protective effects by decreasing the risks of future ischemic events
• Similar benefits are observed in patients w/ IHD without LV dysfunction
B59
D PHARMACOLOGICAL THERAPY - REDUCTION OF INCIDENCE

OF ADVERSE CARDIAC EVENTS (CONT’D)
Angiotensin Receptor Blockers (ARB)
• Recommended in patients w/ SIHD who have indications for, but are intolerant of, ACE inhibitors or angiotensin
receptor-neprilysin inhibitor
• Bind competitively to type 1 angiotensin II receptor which increases plasma renin activity, plasma renin &
angiotensin I & II concentration
• Have cardiovascular protection by decreasing BP equivalent to those achieved by ACE inhibitors & decrease
LV mass & stroke incidences compared w/ beta-blockers & improve outcomes in diabetic nephropathy & heart
failure
• In a combination study of ACE inhibitor & ARB in patients w/ CAD or DM plus additional risk factors w/ no
evidence of CHF, it showed no increase in benefit & had more adverse effects
• ACE inhibitor & ARB are not prescribed together
Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
• Findings from the PARADISE-MI trial, aiming to ascertain the efficacy of ARNI in the treatment of CAD,
showed Sacubitril/Valsartan did not significantly reduce the rate of HF or CV death compared to Ramipril in
patients w/ AMI
• A retrospective study showed that in patients w/ AMI, ARNI was superior to ACE inhibitor or ARB therapy
in reducing the long-term adverse CV outcomes
- Subgroup analysis indicated that AMI patients w/ LVEF <40% & <60 years old benefit more from ARNI
therapy
E PHARMACOLOGICAL THERAPY - REDUCTION OF ISCHEMIA &

RELIEF OF SYMPTOMS
• Reducing symptoms & improving long-term survival are the main goals of anti-anginal therapy
• Anti-ischemic therapy should be based on patient’s BP, heart rate, LV function, comorbidities, concomitant
medical therapy, adherence & preference
- Beta-blockers &/or calcium channel blockers are initially indicated to control heart rate & symptoms
• Conditions that may provoke angina need to be investigated & treated appropriately
CCS
- W/ appropriate treatment of these conditions, angina may resolve & further anti-anginal treatment may be
unnecessary
- If angina is improved but not completely resolved, further therapy should be initiated
• Anti-anginal therapy should be used in conjunction w/ previously mentioned therapies to improve prognosis
Beta-Blockers
• First-line treatment for patients w/ SIHD for long-term relief of symptoms
• Recommended in all patients w/ LV systolic dysfunction (LVEF ≤40%), w/ heart failure, high heart rate or prior
MI, unless there are contraindications
- In patients w/ reduced LV function, use should be limited to Carvedilol, Metoprolol succinate, Bisoprolol
or Nebivolol which have shown to decrease the risk of death in stable optimally treated patients
• Started & continued for at least 1 year in all patients w/ normal LV function after MI or acute coronary syndrome
• Chronic beta-blocker therapy may be considered in all other patients w/ coronary or other vascular diseases
• All beta-blockers appear to be equally effective in the treatment of angina
• Actions:
- Inhibit catecholamines from binding to beta1, beta2 & beta3 receptors which decrease myocardial oxygen
consumption by reducing HR, atrioventricular nodal conduction, myocardial contractility & afterload
- Attenuate cardiovascular remodeling by decreasing LV wall tension w/ long-term use
- Reduction in HR permits more diastolic time & greater coronary perfusion enhancing myocardial oxygen
supply
• Effects:
- Decrease angina onset w/ improvement in the ischemic threshold during exercise & episodes of angina
- Improve survival & decrease recurrent MI in patients w/ LV dysfunction or history of MI
• More effective than dihydropyridine calcium channel blockers in the control of angina, reduction of
cardiovascular events & need for revascularization
• Combination therapy of beta-blockers & dihydropyridine calcium channel blockers decreases dihydropyridine-
induced tachycardia
- Produces increased exercise time & capacity & lowers the rate of cardiovascular events
- Caution is necessary when beta-blocker is combined w/ Verapamil or Diltiazem because of possible
bradycardia, AV block, or excessive fatigue
B60

RELIEF OF SYMPTOMS (CONT’D)
Beta-Blockers (Cont’d)
• Combination therapy of beta-blocker & nitrate can be used in patients w/ SIHD
- Nitrate increases sympathetic tone leading to reflex tachycardia which can be attenuated by the
beta-blockers
- Beta-blockers can increase LV wall tension associated w/ reduced heart rate which is counteracted by the
concomitant use of nitrate
- This combination is more effective than either monotherapy in controlling angina
• Patients w/ pure vasospastic angina (Prinzmetal’s angina) without fixed obstructive lesions should not use
beta-blockers because they are ineffective & may increase tendency to induce coronary vasospasm
• Avoid abrupt withdrawal of beta-blockers because of rebound phenomenon associated w/ increased risk for
AMI & sudden death
- Taper over 1-3 week period w/ the use of sublingual Nitroglycerin or substitution of nondihydropyridine
calcium channel blocker
Calcium Channel Blockers
• Recommended for the relief of anginal symptoms in patients w/ CCS when beta-blockers are contraindicated,
have adverse effects or unsuccessful
• Eg Dihydropyridines (eg Nifedipine, Amlodipine, Felodipine), Nondihydropyridines (eg Verapamil, Diltiazem)
• Drugs of choice, together w/ nitrates, used as monotherapy or in combination in patients w/ Prinzmetal’s
variant angina
• Dihydropyridines are recommended as the 1st step in the management of CCS in patients w/ low heart rate
• Actions:
- Noncompetitively limit calcium ion influx through voltage-dependent L-type calcium channels resulting in
negative inotropic effects, cardiac pacemaker depression, slowing conduction & smooth muscle relaxation
- Improve myocardial oxygen supply by reducing coronary vascular resistance & augmenting epicardial conduit
vessel & systemic arterial blood flow
- Decrease myocardial demand by decreasing myocardial contractility, systemic vascular resistance & arterial
pressure
• Effects: Decrease anginal episodes, increase exercise duration & reduce use of sublingual Nitroglycerin in
patients w/ effort-induced angina
CCS
• Avoid combination treatment w/ Verapamil or Diltiazem & beta-blockers because of possible adverse effects
on AV nodal conduction, heart rate or cardiac contractility
Long-Acting Nitrates
• Recommended for long-term relief of symptoms when initial therapy w/ a beta-blocker &/or nondihydropyridine
calcium channel blocker is contraindicated, poorly tolerated, causes undesirable side effects or inadequate in
controlling angina symptoms
• Effective in the treatment & prevention of all forms of angina
- Can also be used as monotherapy or in combination w/ beta-blockers in patients w/ Prinzmetal’s variant angina
• Actions:
- Both coronary arteriolar & venous vasodilatation decrease myocardial oxygen demand by decreasing LV
volume & arterial pressure via preload reduction
- Improve oxygen supply by their vasodilatory effects on epicardial arteries & collateral vessels
- Have antithrombotic & antiplatelet effects
• Effects:
- Improve exercise tolerance, time to ST-segment depression & time to onset of angina
- Reduce frequency & severity of angina attacks
• Nitrates have greater anti-ischemic effect when used in combination w/ beta-blockers or calcium channel blockers
• Titration of dose is important to have an adequate control of angina w/ the lowest possible dose to limit the
occurrence of headaches & hypotension, avoid nitrate tolerance, worsening of endothelial dysfunction &
facilitate long-term adherence
• Long-term use of nitrates may produce nitrate tolerance resulting in breakthrough angina
- It is necessary to maintain a daily nitrate-free interval of 10-14 hours
- Rebound angina may happen during this nitrate-free period
- Nitrate tolerance does not develop w/ the sublingual route of administration & w/ long-acting nitrates via
sublingual use
• Strict avoidance of co-administration of phosphodiesterase inhibitors such as Sildenafil, Tadalafil or Vardenafil
within 24-48 hours of nitrate administration because of the risk of profound hypotension
• Abrupt discontinuation of nitrates can cause increase in severity of angina
- Severity can be reduced by concomitant administration of other anti-anginal drugs or by tapering of the
long-acting nitrate dosage
B61

RELIEF OF SYMPTOMS (CONT’D)
Short-Acting Nitrates
• Recommended in all patients for immediate relief of acute symptoms &/or situational prophylaxis
• Sublingual & spray Nitroglycerin immediately relieves exertional angina
• Effective for prevention of effort-induced angina when administered 5-10 minutes before activity w/ relief
lasting for 30-40 minutes
• Actions:
- Venodilatation & decreased diastolic filling of the heart (reduced intracardiac pressure) which promotes
subendocardial perfusion
- Coronary vasodilatation & coronary vasospasm antagonism
• Effect: Rapid & effective symptom relief achieved w/ sublingual/buccal tablets or oral spray
• Appropriate instructions on how to use short-acting Nitroglycerin is important
- Explain to patient that it is a short-acting drug without any long-term effects & this may encourage use
• Avoid nitrate tolerance because it blunts the response to short-acting Nitroglycerin
• An attack of angina that does not respond to short-acting Nitroglycerin should be regarded as a possible MI
& immediate medical consultation is necessary
F PHARMACOLOGICAL THERAPY - PATIENTS UNRESPONSIVE TO

INITIAL THERAPY
• For patients who cannot tolerate, have contraindications to, or have symptoms inadequately controlled by
beta-blockers, calcium channel blockers & long-acting nitrates, Ivabradine, Trimetazidine, Nicorandil &
Ranolazine should be considered 2nd-line treatment agents
If Channel Inhibitor
• Eg Ivabradine
• Used for symptomatic treatment of CCS in patients w/ normal sinus rhythm who have contraindications or
intolerance to beta-blockers & whose heart rate is >60 beats/minute
• Effective anti-anginal agent
CCS
• May be used in combination w/ beta-blockers in patients whose resting heart rate remains high
• Actions: Selectively inhibits cardiac pacemaker current If which controls spontaneous diastolic depolarization
in the sinoatrial node
• Effects:
- Regulates heart rate without significant negative inotropic effect & other adverse effects associated w/
beta-blockers
- Reduces heart rate & prolongs diastole thereby improving myocardial oxygen balance
- Has no effect on BP, myocardial contractility or intracardiac conduction parameters
• Reported to be non-inferior to Amlodipine or Atenolol in treating ischemia or angina in patients w/ CCS
3-Ketoacyl-CoA Thiolase (3-KAT) Inhibitor
• Eg Trimetazidine (TMZ)
• Effective anti-anginal therapy when used as monotherapy or in combination w/ other anti-ischemic agents
• Actions:
- Inhibits 3-ketoacyl-CoA thiolase enzyme in myocardial cells which optimizes cardiac metabolism by switching
energy substrate preferences from fatty acid oxidation to glucose oxidation
- Protects the myocardium from ischemic injury which limits myocyte loss during anginal episodes
• Effects: Increases coronary flow reserve which delays the onset of ischemia associated w/ exercise, improves
functional capacity, decreases the frequency of angina & reduces the need for nitrates
• Anti-ischemic effects are not associated w/ heart rate or systolic BP changes
Potassium (K) Channel Activator
• Eg Nicorandil
• Used for the prevention & long-term treatment of angina
• Actions:
- Activates adenosine triphosphate-sensitive potassium channels & promotes systemic venous & coronary
vasodilation through a nitrate moiety
- Increases coronary blood flow & decreases afterload, preload & oxidative injury
• Effects: Has anti-anginal & cardioprotective properties
• Exhibits similar anti-anginal efficacy & safety as those of beta-blockers, calcium channel blockers & oral nitrates
• Tolerance can develop w/ long-term use
B62
F PHARMACOLOGICAL THERAPY - PATIENTS UNRESPONSIVE TO

INITIAL THERAPY (CONT’D)
Sodium (Na) Channel Inhibitor
• Eg Ranolazine
• Indicated for the treatment of chronic angina
• Can be a substitute for beta-blockers for relief of symptoms in patients w/ SIHD if beta-blockers are ineffective,
contraindicated or cause adverse effects
• Can also be used in combination w/ other agents for SIHD
• Good alternative drug in patients w/ SIHD who have bradycardia or hypotension because it has no effect on
HR & BP
• Actions: Inhibits late inward sodium current which indirectly decreases the sodium-dependent calcium current
during ischemic conditions leading to improvement in ventricular diastolic tension & oxygen consumption
• Effects: Decreases the frequency of angina, improves exercise performance & delays the development of
exercise-induced angina & ST-segment depression
• Should only be used for patients who have not achieved an adequate response w/ other anti-anginal drugs
because it can prolong the QT interval
G REVASCULARIZATION
• Objectives are improve survival & diminish or eradicate symptoms
- May be considered in combination w/ optimal medical therapy
• Decision should be based on the patient’s symptoms, presence of significant obstructive coronary artery
stenosis, the amount of related documented ischemia & the expected benefit to prognosis &/or symptoms
- Either non-invasive or invasive functional assessment may be used to evaluate angiographic stenoses before
revascularization, unless very high grade (>90% diameter stenosis)
- For consideration of revascularization, patient w/ high event risk may be considered for invasive testing even
though there are mild or no symptoms
• Clinical (eg age, gender, comorbidities), anatomical (eg single/multivessel disease, SYNTAX score), technical
(eg incomplete/complete vascularization, post CABG/PCI) & environmental factors (eg patient preference,
local cost) should be discussed before the benefit of revascularization can be anticipated
CCS
Indications for Myocardial Revascularization
• Optimal pharmacological therapy is unsuccessful in controlling symptoms
• Non-invasive tests reveal a substantial area of myocardium at risk
- Significant left main stem disease (>50% stenosis)
- Significant proximal multi-vessel disease w/ symptoms of angina or in which large area of ischemia has been
demonstrated on functional testing
- Multi-vessel disease w/ impaired LV function w/ proven viable myocardium
• High likelihood of success & acceptable risk of morbidity & mortality
• Patient prefers an interventional rather than a pharmacological therapy & is fully informed of the benefits &
risks of the procedure
Factors to be Considered for the Selection of the Method of Revascularization
• Risk of peri-procedural morbidity & mortality
• Number of involved coronary vessels
• Likelihood of success w/ consideration of the technical suitability of lesions for angioplasty or surgical bypass
• Risk of restenosis or graft occlusion
• Completeness of revascularization
• Presence of comorbid illnesses
• Expertise of the cardiac & medical team
• Hospital facilities in cardiac surgery & interventional cardiology
• Patient’s preference
Appropriate Use Criteria (AUC) for Revascularization
• Recommended by the American College of Cardiology (ACC) Appropriate Use Criteria Task Force, American
Association for Thoracic Surgery (AATS), American Heart Association (AHA), American Society of
Echocardiography (ASE), American Society of Nuclear Cardiology (ASNC), Society for Cardiovascular
Angiography and Interventions (SCAI), Society of Cardiovascular Computed Tomography (SCCT), & the
Society of Thoracic Surgeons (STS)
• Based on indication, symptoms, present therapy & history of revascularization
B63
G REVASCULARIZATION (CONT’D)
Appropriate Use Criteria (AUC) for Revascularization (Cont’d)
• For patients w/ one-vessel disease:
- PCI only:
- Patients w/ one-vessel disease without proximal left anterior descending coronary artery or proximal left
dominant left circumflex artery involvement w/ low- to high-risk findings on non-invasive testing, w/ no
stress test results or stress tests results are indeterminate & fractional flow reserve of ≤0.80 who are currently
on ≥2 antianginal medications
- Both PCI & CABG:
- Patients w/ one-vessel disease w/ proximal left anterior descending coronary artery or proximal left
dominant left circumflex artery involvement w/ intermediate- to high-risk findings on non-invasive testing
who are currently on 1 antianginal medication
- Patients w/ one-vessel disease w/ proximal left anterior descending coronary artery or proximal left
dominant left circumflex artery involvement w/ low- to high-risk findings on non-invasive testing, w/ no
stress test results or stress test results are indeterminate & fractional flow reserve of ≤0.80 who are currently
on ≥2 antianginal medications
• For patients w/ two-vessel disease:
Findings on No stress test Ischemic Current Recommended
Non-invasive done or stress symptoms Antianginal Revasculariza-
Testing test results present Therapy tion Method
Low- Intermediate- indeterminate None 1 ≥2 PCI CABG
risk to High-risk & FFR ≤0.80 in
both vessels
No proximal + + + + +
left anterior
descending + + + +
coronary + + + + + +
artery
involvement
Proximal left + + + + +
anterior + + + +
CCS
descending
coronary + + + + + +
artery + + + + + +
involvement &
(-) diabetes
Proximal left + +1 +
anterior + + + +
descending
coronary artery + + + + +
involvement & + + + +
(+) diabetes
+ + + + + +
+ + + + + +
1Also applicable for patients w/ antianginal therapy.
Reference: Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate use criteria
for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology
Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society
of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society
of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017 Mar;69.
B64
Appropriate Use Criteria (AUC) for Revascularization (Cont’d)
• For patients w/ three-vessel disease:
Findings on Diabetes Ischemic Current Recommended
Non-invasive symptoms Antianginal Revasculariza-
Testing present Therapy tion Method
Low- Intermediate- Present Absent None 1 ≥2 PCI CABG
risk to High-risk
Low Disease + + + + + +
Complexity + + +1 +
+ + + + +
+ + + + + + +
+ + + + +
+ + + + + +
+ + +1 +
+ + + +
+ + + + + + +
Intermediate + + + +
or High + + + + + +
Disease
Complexity + + +1 +
+ + + + + +
+ + + +1 +
+ + + + + + +
1Also applicable for patients w/ antianginal therapy.
Reference: Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate use criteria
for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology
Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society
of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society
CCS
of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017 Mar;69.
Contraindications to Revascularization
• Patients w/ 1- or 2-vessel disease without significant proximal left anterior descending artery stenosis who are
asymptomatic or w/ only mild symptoms & have no adequate trial of pharmacological therapy or have no
demonstrable ischemia or only a limited area of ischemia/viability on non-invasive testing
• Borderline coronary stenosis (50-70%) in locations other than the left main coronary artery & no ischemia on
non-invasive tests
• Non-significant coronary stenosis (<50%)
• High risk of procedure-related morbidity or mortality (>10-15% mortality risk) unless the risk is balanced by
an expected significant improvement in quality of life or survival
Percutaneous Coronary Intervention (PCI)
• Found to have improved symptoms in patients w/:
- ≥1 significant coronary artery stenoses (≥70% diameter) amenable to revascularization & unacceptable angina
despite optimal medical therapy
- ≥1 significant coronary artery stenoses (≥70% diameter) & unacceptable angina for whom guideline-directed
medical therapy cannot be implemented because of pharmacological therapy contraindications, adverse
effects or patient preferences
- Previous CABG, ≥1 significant coronary artery stenoses (≥70% diameter) associated w/ ischemia & unacceptable
angina despite guideline-directed medical therapy
• Contraindications include:
- Significant unprotected left main CAD (≥50% diameter stenoses) w/ unfavorable anatomy for PCI & patients
are good candidates for CABG
- ≥1 coronary stenoses that are not anatomically or functionally significant (eg <70% diameter non-left main
coronary artery stenosis, fractional flow reserve (FFR) >0.80, no or mild ischemia on non-invasive testing),
involve only the left circumflex or right coronary artery or subtend only a small area of viable myocardium
- Unable to meet anatomic (≥50% diameter left main or ≥70% non-left main stenosis diameter) or physiological
criteria for revascularization (eg abnormal FFR)
• Less invasive procedure compared to CABG w/ lower procedure-related mortality
B65
Percutaneous Coronary Intervention (PCI) (Cont’d)
• PCI is more effective than pharmacological therapy in decreasing symptoms & increasing exercise capacity,
w/ modest improvement in quality of life
- However, PCI has not been demonstrated to improve survival in patients w/ stable angina
- It may also increase the short-term risk of MI & does not lower the long-term risk of MI
Coronary Artery Bypass Graft (CABG)
• May be considered w/ the primary intent of improving survival in patients w/ SIHD w/ severe LV systolic
dysfunction (EF <35%) whether or not viable myocardium is present
• Found to have improved symptoms in patients w/:
- >1 significant coronary artery stenoses (>70% diameter) amenable to revascularization & unacceptable angina
despite guideline-directed medical therapy
- ≥1 significant coronary artery stenoses (≥70% diameter) & unacceptable angina for whom guideline-directed
medical therapy cannot be implemented because of pharmacological therapy contraindications, adverse
effects or patient preferences
- Complex 3-vessel CAD, w/ or without proximal LAD artery involvement, who are good candidates for CABG
- Previous CABG, >1 significant coronary artery stenoses (>70% diameter) not amenable to PCI & unacceptable
angina despite guideline-directed medical therapy
• Contraindications include:
- ≥1 coronary stenoses that are not anatomically or functionally significant (eg <70% diameter non-left main
coronary artery stenosis, fractional flow reserve (FFR) >0.80, no or mild ischemia on non-invasive testing),
involve only the left circumflex or right coronary artery or subtend only a small area of viable myocardium
- Unable to meet anatomic (≥50% diameter left main or ≥70% non-left main stenosis diameter) or physiological
criteria for revascularization (eg abnormal FFR)
• CABG is more effective than pharmacological therapy for relieving anginal symptoms in patients w/ left main
CAD or 3-vessel CAD
- Presence of LV dysfunction increases the absolute prognostic advantage of surgery over pharmacological therapy
- Concurrent administration of guideline-directed medical therapy may substantially improve long-term
outcomes in patients treated w/ CABG compared to those who are receiving pharmacological therapy alone
• CABG has shown to reduce symptoms & ischemia, improve quality of life & provide a better prognosis especially
CCS
in moderate- to high-risk patients
H FOLLOW-UP & MONITORING

• Patients w/ SIHD should have regular follow-up every 4-6 months during the first year of therapy, every 6-12 months
after the first year if the patient is stable & earlier if there is a change in the symptoms or functional capacity
• Evaluation includes:
- Assessment of symptoms & clinical function
- Surveillance for complications such as arrhythmias & heart failure
- Monitoring of cardiac risk factors
- Assessment of the adequacy & compliance to lifestyle modifications & medical therapy
• Periodic screening of comorbidities that are prevalent in patients w/ SIHD such as DM, depression & chronic
renal disease
• Reinforce therapies that help control risk factors such as dyslipidemia, hypertension & DM
• Patients at risk (eg recent acute coronary syndrome or revascularization, heart failure) should have medically-
supervised programs (cardiac rehabilitation) & physician-directed home-based exercise programs
• Resting ECG at 1-year or longer intervals between studies in patients w/ stable symptoms can also be performed
- Additional ECG is suggested if patient experiences arrhythmia, anginal symptoms or if therapy has been
modified
• Exercise ECG or stress imaging is recommended if there are changes in frequency of symptoms or new
symptoms occur
- Repeat exercise ECG may be done after 2 years if stable
- Stress test may be done for reference 1-3 months post revascularization &/or periodically for ischemia
reassessment
• Reassessment of prognosis via stress test every 3-5 years for low-risk/asymptomatic patients
• Assessment of LVEF & segmental wall motion by echocardiography or radionuclide imaging is recommended
in patients w/ new or worsening heart failure or evidence of intervening MI by history or ECG
• For patients w/ debilitating angina unresponsive to optimal medical therapy & revascularization, consider
using an enhanced external counterpulsation (EECP), a reducer device for coronary sinus constriction, or
spinal cord stimulation to improve symptoms
- Transmyocardial revascularization is not recommended in patients w/ refractory angina
B66
Dosage Guidelines
ACE INHIBITORS1,2
Drug Dosage Remarks
Benazepril Initial dose (patient not on diuretic): Adverse Reactions
10-20 mg PO 24 hrly • CV effects (hypotension, palpitations, chest
Initial dose (patient taking diuretic): pain, arrhythmia); CNS effects (fatigue,
5 mg PO 24 hrly headache, dizziness); GI effects (N/V, taste
Maintenance dose: disturbances, flatulence); Resp effects
20-40 PO mg 12-24 hrly (persistent dry cough, upper resp tract
Max dose: 80 mg/day symptoms); Dermatologic effects (skin rashes,
angioedema, erythema multiforme, toxic
Captopril Initial dose: epidermal necrolysis); Hypersensitivity
12.5 mg PO 12 hrly reactions; Renal effect (renal impairment);
May increase dose gradually every 2-4 wk Electrolyte disturbances (hyperkalemia,
Maintenance dose: hyponatremia); Blood disorders
25-50 mg PO 12 hrly Special Instructions
Max dose: 150 mg/day • Patients w/ HF & those who may be salt or
Cilazapril Initial dose: water depleted (taking diuretic or on dialysis)
1 mg PO 24 hrly x 2 days may experience hypotension during initial
Maintenance dose: stages of ACE inhibitor therapy
2.5-5 mg PO 24 hrly - Start treatment only under close medical
supervision; in these patients use a low dose
Delapril 15-30 mg PO 12 hrly & have the patient in a supine position
Enalapril Initial dose (patient not on diuretic): • Avoid in patients w/ aortic stenosis or outflow
5 mg PO 24 hrly tract obstruction & should generally be avoided
Initial dose (patient taking diuretic): in suspected or actual renovascular disease
2.5 mg PO 24 hrly • Use w/ caution in patients w/ history of
Maintenance dose: hereditary or idiopathic angioedema, porphyria,
CCS
10-20 mg PO 24 hrly collagen vascular disease, severe CHF
Max dose: 40 mg/day • Renal function should be assessed prior to
administration of ACE inhibitors & should be
Fosinopril Initial dose: monitored during therapy
10 mg PO 24 hrly - Patient w/ renal disease or taking high doses
Maintenance dose: should be monitored regularly for proteinuria
10-40 mg PO 24 hrly • Monitor BP w/ the 1st dose & WBC & urinary
protein before & during therapy
- Take the 1st dose at bedtime for there may be
precipitous fall in blood pressure
1If possible, discontinue diuretics 2-3 wk before initiating therapy w/ ACE Inhibitors. Otherwise, monitor patient closely during therapy.
2Combinations of ACE inhibitor & thiazide diuretic; ACE inhibitor & calcium antagonist are available. .

B67
Dosage Guidelines
ACE INHIBITORS1,2 (CONT’D)

Drug Dosage Remarks
Imidapril Initial dose: 5 mg PO 24 hrly Adverse Reactions
Maintenance dose: 10 mg PO 24 hrly • CV effects (hypotension, palpitations, chest
Max dose: 20 mg/day pain, arrhythmia); CNS effects (fatigue,
headache, dizziness); GI effects (N/V, taste
Lisinopril Initial dose (patient not on diuretic): disturbances, flatulence); Resp effects
5-10 mg PO 24 hrly (persistent dry cough, upper resp tract
Initial dose (patient taking diuretic): symptoms); Dermatologic effects (skin rashes,
5 mg PO 24 hrly angioedema, erythema multiforme, toxic
Maintenance dose: 20 mg PO 24 hrly epidermal necrolysis); Hypersensitivity
reactions; Renal effect (renal impairment);
Max dose: 80 mg/day Electrolyte disturbances (hyperkalemia,
Moexipril Initial dose (patient not on diuretic): hyponatremia); Blood disorders
7.5 mg PO 24 hrly Special Instructions
Initial dose (patient taking diuretic): • Patients w/ heart failure & those who may be
3.75 mg PO 24 hrly salt or water depleted (taking diuretic or on
Maintenance dose: 7.5 -30 mg PO 24 hrly dialysis) may experience hypotension during
(May give dose divided 12 hrly if control is initial stages of ACE inhibitor therapy
inadequate w/ single daily dose) - Start treatment only under close medical
supervision; in these patients use a low
Perindopril3 Initial dose: 4-5 mg PO 24 hrly dose & have the patient in a supine
May increase to 8-10 mg PO 24 hrly after position
1 mth of treatment • Avoid in patients w/ aortic stenosis or
Max dose: 8-10 mg/day outflow tract obstruction & should generally
Quinapril Initial dose (patient not on diuretic): be avoided in suspected or actual
renovascular disease
CCS
10 mg PO 24 hrly
• Use w/ caution in patients w/ history of
Initial dose (patient taking diuretic):
hereditary or idiopathic angioedema,
5 mg PO 24 hrly porphyria, collagen vascular disease, severe
Maintenance dose: CHF
20-40 mg PO 12-24 hrly • Renal function should be assessed prior to
Max dose: 80 mg/day administration of ACE inhibitors & should
be monitored during therapy
Ramipril Initial dose: 1.25-2.5 mg PO 24 hrly
- Patient w/ renal disease or taking high
Maintenance dose: 2.5-5 mg PO 24 hrly
doses should be monitored regularly for
Max dose: 10 mg/day proteinuria
Trandolapril Initial dose (patient not on diuretic): • Monitor BP w/ the 1st dose & WBC &
1 mg PO 24 hrly urinary protein before & during therapy
Initial dose (patient taking diuretic): - Take the 1st dose at bedtime for there may
0.5 mg PO 24 hrly be precipitous fall in blood pressure
Maintenance dose: 1-2 mg PO 24 hrly
Max dose: 4 mg/day
2Combinations of ACE inhibitor & thiazide diuretic; ACE inhibitor & calcium antagonist are available.
3Combination w/ Bisoprolol is available..

B68
Dosage Guidelines

Drug Dosage Remarks
Other Combinations
Perindopril/ Perindopril 5 mg/Amlodipine 5 mg/ Adverse Reactions
Amlodipine/ Atorvastatin 10 mg • GI effects (constipation, dyspepsia, N/V, diarrhea);
Atorvastatin Perindopril 5 mg/Amlodipine 5 mg/ CNS effects (headache, dizziness, paresthesia,
Atorvastatin 20 mg asthenia); Musculoskeletal effects (myalgia, arthralgia,
Perindopril 10 mg/Amlodipine 5 mg/ back pain, joint & ankle swelling); Metabolic effects
Atorvastatin 20 mg (hyperglycemia, abnormal LFT, increased blood
Perindopril 10 mg/Amlodipine 10 mg/ creatine); CV effects (palpitations, hypotension); Resp
Atorvastatin 20 mg effects (nasopharyngitis, cough, dyspnea); Other
Perindopril 10 mg/Amlodipine 10 mg/ effects (hypersensitivity, epistaxis, flushing, edema,
Atorvastatin 40 mg visual impairment, tinnitus, rash, pruritus)
• Use w/ caution in patients w/ collagen vascular
disease, on immunosuppressant therapy,
Allopurinol or Procainamide
decreased renal function; interstitial lung disease on
long-term therapy
• Monitor glycemic control & LFTs periodically
• Avoid in patients w/ hypersensitivity, liver disease,
severe hypotension, hemodynamically unstable
heart failure, history of angioedema, significant
bilateral renal artery stenosis; on Sacubitril/Valsartan
CCS
ANGIOTENSIN II ANTAGONISTS
Drug Dosage Remarks
Azilsartan Initial dose: 40 mg PO 24 hrly Adverse Reactions
medoxomil May increase up to 80 mg PO 24 hrly • Usually mild & transient: CNS effects (dizziness,
Candesartan Initial dose: 8 mg PO 24 hrly headache); CV effect (dose-related orthostatic
hypotension which may occur particularly in
Maintenance dose: 8-16 mg PO 24 hrly patients w/ volume depletion); Renal impairment
Max dose: 32 mg/day • Rare effects: Rash, angioedema, elevated LFTs,
Eprosartan Maintenance dose: 400-800 mg PO myalgia
24 hrly or divided 12 hrly Special Instructions
Max dose: 800 mg/day • Patients w/ volume depletion (eg high-dose
Irbesartan Initial dose: 150 mg PO 24 hrly diuretic therapy) may experience hypotension &
Maintenance dose: 150-300 mg PO 24 hrly should be started on low dose
• Use w/ caution in patients w/ renal artery
Losartan 50 mg PO 24 hrly stenosis, renal impairment or hepatic impairment
May increase to 100 mg PO 24 hrly or • Avoid in patients w/ bilateral renal artery stenosis
divided 12 hrly or primary hyperaldosteronism
Olmesartan Initial dose: 20 mg PO 24 hrly • Serum K should be monitored especially in the
medoxomil May increase to 40 mg PO 24 hrly elderly, patients w/ renal impairment & K-sparing
diuretics should be avoided
Telmisartan 20-40 mg PO 24 hrly
Max dose: 80 mg/day
Valsartan Initial dose: 80 mg PO 24 hrly

B69
Dosage Guidelines
ANTIPLATELET AGENTS
Drug Dosage Remarks
Aspirin 75-325 mg PO 24 hrly Adverse Reactions
• GI effects (GI upset which may be minimized by administering
w/ food & w/ use of enteric-coated formulation, also GI
irritation including erosion, ulceration, etc); Hematologic
effects (increase in bleeding time, decrease in platelet
adhesiveness, hemorrhage); Hypersensitivity reactions
• Contraindicated in patients w/ active pathological bleeding (eg
peptic ulcer, intracranial hemorrhage), known allergy,
hemophilia, hemorrhagic disorders, severe renal or hepatic
impairment
combination w/ Warfarin, Heparin, thrombolytics, NSAIDs &
other drugs that increase the risk of bleeding
Clopidogrel 75 mg PO 24 hrly Adverse Reactions
• Hematologic effects (hemorrhage, purpura, epistaxis, blood
dyscrasias, including neutropenia, thrombotic
thrombocytopenic purpura have occurred); Dermatologic
effects (rash, pruritus); GI effects (abdominal pain, N/V,
dyspepsia, constipation)
• Contraindicated in patients w/ active bleeding or severe liver
impairment
• Concurrent use of drugs known to inhibit CYP2C19 (eg
CCS
Omeprazole, Esomeprazole, Cimetidine, Fluconazole,

Ketoconazole, Voriconazole, Etravirine, Felbamate, Fluoxetine,
Fluvoxamine & Ticlopidine) should be avoided
- Separating the time of administration between the drugs
does not reduce the chance of interaction
Triflusal 600 mg PO 24 hrly or in Adverse Reactions
divided doses • GI effects (dyspepsia, abdominal pain, N/V, flatulence,
or constipation); CNS effects (headache, anorexia)
900 mg PO 24 hrly or in Special Instructions
divided doses • Contraindicated in patients w/ active bleeding & those w/
salicylate hypersensitivity
• Use w/ caution in patients w/ renal or hepatic impairment

B70
Dosage Guidelines
BETA-BLOCKERS
Drug Dosage Remarks
Acebutolol Initial dose: 200 mg PO 12 hrly or 400 mg PO Adverse Reactions
24 hrly • CNS effects (fatigue, depression,
Maintenance dose: 200-600 mg PO 12 hrly dizziness, confusion, sleep
Max dose: 1200 mg/day divided 12 hrly disturbances); CV effects (heart failure,
heart block, bradycardia, coldness of
Atenolol1 50-100 mg PO 12-24 hrly extremities, male impotence); Resp
Max dose: 200 mg/day effects (bronchospasm in susceptible
Betaxolol 10-20 mg PO 24 hrly patients & drugs w/ beta1 selectivity
Max dose: 40 mg/day should be used w/ caution in these
patients); GI effects (N/V, diarrhea,
Bisoprolol2 5-10 mg PO 24 hrly constipation); Metabolic effects (can
Max dose: 20 mg/day produce hyper- or hypoglycemia,
changes in serum cholesterol &
Bupranolol 100-400 mg PO 24 hrly
triglycerides)
Carteolol 5-10 mg PO 24 hrly or divided 12 hrly Special Instructions
May be increased to 20 mg PO 24 hrly • Contraindicated in severe bradycardia,
Max dose: 30 mg/day preexisting high degree of AV block,
Carvedilol3 Initial dose: 12.5 mg PO 12 hrly x 2 days sick sinus syndrome & severe, unstable
LV failure
Then increase to 25 mg PO 12 hrly
• Use w/ caution in patients w/
May increase dose every 2 wk thereafter, if bronchospasm, asthma or obstructive
required up to: airway diseases
Max dose: 100 mg/day PO divided 12 hrly • Use w/ caution in 1st-degree block,
Celiprolol Initial dose: 200 mg PO 24 hrly depression, patients w/ PAD & patients
on Insulin
CCS
May increase dose to 400 mg PO 24 hrly
• Beta-blockers may mask the symptoms
Labetalol Initial dose: 100 mg PO 12 hrly
of hyperthyroidism & hypoglycemia &
May increase dose after 2 wk to 200-400 mg PO may aggravate psoriasis
12 hrly
• Patients on long-term treatment
Max dose: 2400 mg/day should not discontinue abruptly;
Metoprolol3 Regular release: 50-100 mg PO 8-12 hrly should discontinue gradually over
Maintenance dose: 100-200 mg PO 24 hrly 1-2 wk
Extended-release: 50-200 mg PO 24 hrly
Max dose: 400 mg/day or 95-190 mg PO 24 hrly
up to 380 mg PO 24 hrly
Nadolol Initial dose: 40 mg PO 24 hrly
May increase dose by 40-80 mg every 3-7 days
until adequate response is achieved
Max dose: 160-240 mg/day
1Combination w/ Nifedipine is available.
2Combination w/ Perindopril is available.
3Combination w/ Ivabradine is available.

B71
Dosage Guidelines
BETA-BLOCKERS (CONT’D)
Drug Dosage Remarks
Pindolol 2.5-5 mg PO 8 hrly Adverse Reactions
Maintenance dose: 15-40 mg PO • CNS effects (fatigue, depression, dizziness, confusion,
in divided doses sleep disturbances); CV effects (HF, heart block,
Max dose: 40 mg/day bradycardia, coldness of extremities, male impotence);
Resp effects (bronchospasm in susceptible patients &
Propranolol Regular release: drugs w/ beta1 selectivity should be used w/ caution in
Initial dose: 40 mg PO 8-12 hrly these patients); GI effects (N/V, diarrhea, constipation);
May increase to 120-240 mg/day PO Metabolic effects (can produce hyper- or hypoglycemia,
Max dose: 320 mg/day changes in serum cholesterol & triglycerides)
Extended-release: Special Instructions
Initial dose: 80 mg PO 24 hrly • Contraindicated in severe bradycardia, preexisting high
May increase to 160 mg PO 24 hrly degree of AV block, sick sinus syndrome & severe,
unstable LV failure
• Use w/ caution in patients w/ bronchospasm, asthma or
Sotalol Initial dose: 80-160 mg PO obstructive airway diseases, 1st-degree block,
24 hrly or divided 12 hrly depression, patients w/ PVD & patients on Insulin
May increase dose gradually at • Beta-blockers may mask the symptoms of
2-3 day intervals to 80-160 mg PO hyperthyroidism & hypoglycemia & may aggravate
12 hrly psoriasis
• Patients on long-term treatment should not discontinue
abruptly; should discontinue gradually over 1-2 wk
CALCIUM ANTAGONISTS1
CCS
Drug Dosage Remarks

Benzothiazepine
Initial dose: 30-60 mg PO 8 hrly • CV effects (depression of cardiac function,
May increase to 360 mg/day PO hypotension, worsening HF, edema, flushing,
in divided doses bradycardia); GI effects (constipation, abdominal
Max dose: 480 mg/day pain); CNS effects (headache, dizziness)
Extended-release (24 hrly): • HR-modulating Ca antagonists (eg Diltiazem,
Gallopamil & Verapamil): AV dissociation, AV
120-180 mg PO 12-24 hrly block, bradycardia & sinus node dysfunction
or 100-300 mg PO 24 hrly • Short-acting dihydropyridine agents should be
Extended-release (12 hrly): avoided because they have the potential to enhance
90 mg PO 12 hrly risk of adverse cardiac events
• Contraindicated in patients w/ overt decompensated
HF, though vasoselective dihydropyridines (eg
Amlodipine, Felodipine) are tolerated in patients w/ a
decreased LV ejection fraction
patients w/ bradycardia, sinus node dysfunction &
AV nodal block
1Combinations of calcium antagonist & ACE inhibitor; calcium antagonist & angiotensin II antagonist; calcium antagonist & be-
ta-blocker are available.

B72
Dosage Guidelines
CALCIUM ANTAGONISTS1 (CONT’D)

Drug Dosage Remarks
Dihydropyridines
Amlodipine2 Initial dose: 5 mg PO 24 hrly Adverse Reactions
Max dose: 10 mg/day • CV effects (depression of cardiac function,
Benidipine 4 mg PO 12 hrly hypotension, worsening HF, edema, flushing,
bradycardia, short-acting dihydropyridine agent, eg
Felodipine Initial dose: 5 mg PO 24 hrly Nifedipine, can induce tachycardia & palpitations); GI
Max dose: 10 mg/day effects (constipation, abdominal pain); CNS effects
(headache, dizziness)
Levamlodipine 2.5 mg PO 24 hrly
• HR-modulating Ca antagonists (eg Diltiazem,
May be increased up to 5 mg
Gallopamil & Verapamil): AV dissociation, AV block,
24 hrly if necessary
bradycardia & sinus node dysfunction
Nicardipine Regular release: • Levamlodipine: Tachycardia, cough, breathing
Initial dose: 20 mg PO 8 hrly difficulty, vertigo, headache, facial puffiness,
Maintenance dose: cheerlessness
30 mg PO 8 hrly • Short-acting dihydropyridine agents should be
May increase to 60-120 mg in avoided because they have the potential to enhance
divided doses risk of adverse cardiac events
Extended-release: Special Instructions
40 mg PO 12 hrly • Contraindicated in patients w/ overt decompensated
Nifedipine Regular release: Amlodipine, Felodipine) are tolerated in patients w/ a
Initial dose: 5-10 mg PO 8 hrly decreased LV ejection fraction
May increase to 20 mg PO 8 hrly • HR-modulating Ca antagonists are contraindicated in
Extended-release (24 hrly): patients w/ bradycardia, sinus node dysfunction & AV
CCS
Initial dose: 20-30 mg PO nodal block
24 hrly • Levamlodipine: Avoid concomitant use w/
May increase to 90-120 mg PO Isoprinoline & Dopamine
24 hrly
Extended-release (12 hrly):
10-40 mg PO 12 hrly
Nisoldipine 10 mg PO 24 hrly
May increase to 20-40 mg PO
24 hrly
Phenylalkylamines
Gallopamil Regular release: 25-50 mg PO
6-12 hrly
Extended-release: 100 mg PO
12-24 hrly
Verapamil Regular release:
80-120 mg PO 8 hrly
Extended-release: 120-480 mg
PO divided 12-24 hrly
2Combination w/ Atorvastatin is available.

B73
Dosage Guidelines
CARDIAC DRUGS
Drug Dosage Remarks
Amino Acid Derivative
L-carnitine 660 mg PO 8 hrly Special Instructions
• Contraindicated in patients w/ hypersensitivity to
L-carnitine
NITRATES (ORAL - LONG-ACTING)

Drug Dosage Remarks
Glyceryl Modified-release cap/tab: Adverse Reactions
trinitrate 2.5-6.5 mg PO 6-8 hrly • CNS effects (headache which usually decreases w/
(Nitroglycerin, Extended-release tab: long-term administration, lightheadedness,
GTN, NTG) dizziness, syncope); rarely CV effects (bradycardia,
Initial dose: 2.6 mg PO 12 hrly
hypotension); GI effects (N/V, bowel incontinence,
May increase to 2-3 tabs PO xerostomia)
12 hrly
• Nitrate tolerance usually develops w/ long-term use
Isosorbide Regular release: 2.5-40 mg PO & dosing w/ adequate nitrate-free interval is
dinitrate 6-8 hrly recommended
Extended-release: 20 mg PO Special Instructions
8-12 hrly or 40 mg PO 12-24 hrly • Dosing to overcome nitrate tolerance: Recommend
or 120 mg PO 24 hrly giving last dose of short-acting agents at 7 PM;
(Dose will depend on administer 2x/day rather than 4x/day; administer
formulation)
CCS
extended-release prep once in the morning

Isosorbide Regular release: • Avoid in patients w/ severe hypotension,
5-mononitrate Initial dose: 10 mg PO 12 hrly hypovolemia, marked anemia, HF due to
(Isosorbide May increase to 20-40 mg PO obstruction or raised intracranial pressure due to
mononitrate) 8-12 hrly depending on head trauma or hemorrhage
formulation • Use w/ caution in patients w/ severe renal or hepatic
Max dose: 120 mg/day dysfunction, hypothyroidism, malnutrition or
hypothermia
Extended-release: 30-120 mg PO
24 hrly depending on - Use w/ caution in post-MI w/ endothelial
formulation dysfunction & if BP drops following use
• Co-administration w/ phosphodiesterase type 5
inhibitors (eg Sildenafil, Vardenafil, Tadalafil) is
contraindicated

B74
Dosage Guidelines

Available
Drug Dosage Remarks
Strength
Glyceryl 400, 500, Acute anginal attack: 400-600 mcg Adverse Reactions
trinitrate 600 mcg SL every 5 min until cessation of • CNS effects (headache,
(Nitroglycerin, sublingual pain or side effects occur lightheadedness, dizziness,
GTN, NTG) (SL) tab Max dose: 3 doses within 15 min syncope); rarely CV effects
Prophylaxis: 400-600 mcg SL 5-10 (bradycardia, hypotension); GI
min prior to activity effects (N/V, bowel
incontinence, xerostomia)
400 mcg/ Acute anginal attack:
dose SL Special Instructions
1-2 sprays (400-800 mcg) SL
spray • Avoid in patients w/ severe
May repeat w/ 1 spray every 5 min hypotension, hypovolemia,
until cessation of pain or side effects marked anemia, HF due to
occur obstruction or raised intracranial
Max dose: 3 doses within 15 min pressure due to head trauma or
Prophylaxis: 1 spray SL 5-10 min hemorrhage
prior to activity • Use w/ caution in patients w/
Isosorbide 5, 10 mg SL Acute anginal attack: severe renal or hepatic
dinitrate tab 2.5-10 mg SL every 5-10 min until dysfunction, hypothyroidism,
cessation of pain or side effects malnutrition or hypothermia
occur • Co-administration w/
Max dose: 3 doses within 15-30 min phosphodiesterase inhibitors (eg
Sildenafil) is contraindicated
Prophylaxis: 2.5-10 mg SL prior to within 24-hr interval after taking
activity a nitrate preparation
1.25 mg/dose Acute anginal attack: Acute attacks:
CCS
buccal spray 1-3 sprays (1.25-3.75 mg) into the • Instruct patient to sit down &
buccal cavity; waiting 30 sec use medication at 1st sign of
between sprays. Do not inhale angina attack
medication • Patient should be made aware
Prophylaxis: 1-3 sprays that dose may be repeated in
(1.25-3.75 mg) into the buccal 5-10 min w/ max of 3 doses
cavity prior to activity; waiting 30 given
sec between sprays. Do not inhale • Patient should seek emergency
medication medical treatment if pain does
not subside
NITRATES (TOPICAL - LONG-ACTING)

Available
Drug Dosage Remarks
Strength
Glyceryl 5 mg/24 hr 5-20 mg/24 hr (1-2 patches) Adverse Reactions
trinitrate patch applied 24 hrly usually in the • See oral prep on previous page
(Nitroglycerin, (0.2 mg/hr/ morning • Topical prep: Contact dermatitis,
GTN, NTG) day) To prevent tolerance: Patch-free local irritation & erythema
10 mg/24 hr period of 8-12 hr, usually at night Special Instructions
patch every 24 hr is recommended
(0.4 mg/hr/ • See oral prep on previous page
day)

B75
Dosage Guidelines
OTHER ANTI-ANGINAL DRUGS

Drug Dosage Remarks
3-KAT Inhibitor
Trimetazidine Regular release: Adverse Reactions
20 mg PO 8 hrly • Rarely, GI effects (N/V), tiredness, headache, vertigo, sleep
Modified-release: disorder, orthostatic hypotension, skin rash
35 mg PO 12 hrly Special Instructions
• Contraindicated in patients w/ known hypersensitivity,
pregnancy & lactation
If Channel Inhibitor
Ivabradine1 Initial dose: Adverse Reactions
5 mg PO 12 hrly • Luminous phenomena in visual field (phosphenes); CNS
May increase dose after effects (blurred vision, headache, dizziness); CV effects
3-4 wk to 7.5 mg PO (bradycardia, 1st-degree AV block, ventricular extrasystole)
Titrate dose depending • Should be taken w/ food; avoid excessive consumption of
on patient’s heart rate grapefruit juice
• Use w/ caution in patients w/ atrial fibrillation, 2nd-degree
AV block, CHF, stroke, retinitis pigmentosa, galactose
intolerance, hypotension, congenital QT syndrome, moderate
hepatic insufficiency, severe renal impairment
• Contraindicated in patients w/ bradycardia, cardiogenic
shock, acute MI, severe hypotension, severe hepatic
insufficiency, sick sinus syndrome, SA block, severe heart
CCS
failure, pacemaker, unstable angina, 3rd-degree AV block

• Avoid use w/ azole antifungals, macrolides, HIV protease
inhibitors, Diltiazem, Verapamil, Rifampicin, barbiturates,
Phenytoin, St John’s wort
Other Vasodilator
Molsidomine 1-4 mg PO 6-8 hrly or Adverse Reactions
2-4 mg IV as a single • CV effects (arterial hypotension, orthostatic hypotension);
dose Hypersensitivity effects (pruritus, rash); CNS effects
May give additional (headache, vertigo); GI effects (anorexia, nausea)
2 mg IV if necessary Special Instructions
Max dose: 40 mg/day • Use w/ caution in patients w/ liver insufficiency
1Combination w/ Metoprolol or Carvedilol is available. Please see the latest MIMS for specific formulations & prescribing information.

B76
Dosage Guidelines
OTHER ANTI-ANGINAL DRUGS (CONT’D)

Drug Dosage Remarks
Potassium Channel Activator
Nicorandil Initial dose: Adverse Reactions
10 mg PO 12 hrly • CNS effects (headache which is usually transitory, weakness);
Maintenance dose: CV effects (vasodilation, flushing, hypotension, increase in
10-20 mg PO 12 hrly HR); GI effects (N/V, oral ulcerations)
Max dose: Special Instructions
30 mg PO 12 hrly • Avoid in patients w/ cardiogenic shock, LV failure w/ low
filling pressures & hypotension
• Use w/ caution in patients w/ low SBP, hypovolemia or acute
pulmonary edema
Sodium Channel Inhibitor
Ranolazine 375 mg PO 12 hrly Adverse Reactions
Titrate dose to 500 mg • CNS effects (dizziness, headache, vertigo); GI effects
PO 12 hrly after 2-4 wk (constipation, N/V, abdominal pain, dry mouth); CV effects
Max dose: (syncope, bradycardia, palpitations, hypotension, peripheral
1500 mg/day edema); Other effects (tinnitus, dyspnea, hematuria)
500 mg PO 12 hrly • Use w/ caution in patients w/ renal disease, in patients w/
history of malignant neoplasms & adenomatous polyps
May increase to
1000 mg PO 12 hrly as • Contraindicated in patients w/ significant hepatic impairment
needed • Avoid co-administration w/ azoles, macrolides, Nefazodone,
Max dose: Nelfinavir, Rifampicin, Phenytoin, Phenobarbital,
Carbamazepine, St John’s wort
CCS
2000 mg/day

B77
Dyslipidemia (1 of 24)
1
Patient’s lipid profile is obtained
2
RISK STRATIFICATION
Determine ASCVD risk categories
3
No Does LDL-C level
warrant drug
therapy?
A Lifestyle modifications
Yes
A Lifestyle modifications &

B LDL-C-lowering pharmacological therapy, w/ or without
C TG-lowering & HDL-C-raising pharmacological therapy
LIPID PROFILE IN 6-8 WEEKS
4 • Continue therapy*
LDL-C goal Yes • Patient monitoring every
achieved? 6-12 months as required
No
A Lifestyle modifications
B Intensified LDL-C-lowering
pharmacological therapy
• Start pharmacotherapy if not yet started
PATIENT MONITORING EVERY 6-8 WEEKS
4
INTERNIST No LDL-C goal Yes
REFERRAL achieved? * If LDL-C is on target but TG is >200 mg/dL, add
fibrate to statin therapy.
B78
DYSLIPIDEMIA
• An abnormality in lipoprotein metabolism that results in elevations of low-density lipoprotein cholesterol
(LDL-C), total cholesterol (TC), triglycerides (TG), &/or non-high-density lipoprotein cholesterol (non-HDL-C)
levels, or significantly reduced high-density lipoprotein cholesterol (HDL-C) levels
• Increase in serum concentration of TC, LDL, TG or non-HDL-C is equivalent to increased risk for cardiovascular
diseases
Types of Dyslipidemia
Hypercholesterolemia
• Increased LDL, TC, & LDL-C
Hypertriglyceridemia
• A state where very-low-density lipoproteins (VLDL) & TG are significantly increased
- Desirable level: TG <1.7 mmol/L (<150 mg/dL)
- Moderate/high hypertriglyceridemia: TG 1.7-5.6 mmol/L (150-499 mg/dL)
- Severe/very high hypertriglyceridemia: TG >5.6 mmol/L (≥500 mg/dL)
• Etiologic factors include heredity, obesity, type 2 diabetes mellitus (T2DM), high carbohydrate diet, renal
disease, medications (eg corticosteroids, Tamoxifen, Ciclosporin, estrogens, protease inhibitors, Isotretinoin)
Combined Dyslipidemia
• Increased LDL, VLDL, TC, LDL-C, & TG
Pathophysiology
• Etiology depends on the type of dyslipidemia
• Hereditary disorders associated w/ dyslipidemia include familial hypercholesterolemia, familial
hypertriglyceridemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, chylomicronemia
• Secondary causes include DM, diet, alcohol intake, hypothyroidism, renal failure, obstructive liver disease, Cushing’s
syndrome, metabolic syndrome, medications (glucocorticoids, beta-blockers, thiazides, estrogen therapy)
1 LIPID PROFILE
• Lipid profile is obtained from an individual w/ DM, cardiovascular disease (CVD), cerebrovascular disease, or other
CVD risk factor(s) or from an individual w/ family history or clinical evidence of familial hypercholesterolemia
- Cardiovascular diseases include coronary heart disease (CHD), myocardial infarction (MI), coronary
insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), peripheral artery
disease (PAD), & heart failure
Measure Plasma Lipids
• Total cholesterol (TC)
• High-density lipoprotein cholesterol (HDL-C)
• Non-HDL-C: TC - HDL-C
• Triglycerides (TG)
• Low-density lipoprotein cholesterol (LDL-C) is derived by Friedewald formula: LDL-C (mmol/L) = TC - HDL-C
- [TG x 0.45] or LDL-C (mg/dL) = TC - HDL-C - [TG x 0.2]
Considerations
• Fasting or a non-fasting plasma lipid profile can be used in screening & in risk estimation
- Non-fasting samples can be used to document baseline lipid levels before initiation of statin therapy in
patients w/ clinical atherosclerotic cardiovascular disease (ASCVD) DYSLIPIDEMIA
- Fasting lipid profile is recommended for initial evaluation in patients w/ a family history of premature ASCVD,
genetic hyperlipidemia or for follow-up of patients w/ hypertriglyceridemia
- TC & HDL-C can be measured accurately at any time of the day
- TG levels are affected by food resulting to a higher plasma level of about 0.3 mmol/L (27 mg/dL), by alcohol
intake within 24 hours prior to measurement & by smoking during the fasting state
- Non-HDL cholesterol can be computed even from a non-fasting lipid profile
• Friedewald formula can only be used if TG <4.5 mmol/L (<400 mg/dL) but is only recommended for use during
fasting states
• In patients w/ TG >4.5 mmol/L (>400 mg/dL), non-HDL-C >3.37 mmol/L (>130 mg/dL) should be the alternative
primary target of treatment
• If TG is >2.3 mmol/L (>200 mg/dL), non-HDL-C is a better indicator of total atherogenic burden
• Plasma measurement of cholesterol is 3% lower than serum measurements
• Levels will be affected by recent acute illness (eg fever, surgery, stroke) & drugs (eg beta-blockers, steroids, thiazides)
• If possible, measure lipids within 24 hours of MI
• ≥1 measurement is needed to make hyperlipidemic diagnosis because of biological variability
Dyslipidemia Screening
• The U.S. Preventive Services Task Force recommends that if the risk of CHD is increased, screen men 20-35
years old & women 20-45 years old
• More frequent assessments are needed for all patients w/ CVD risk factors & those w/ a family history of
premature CVD (definite MI or sudden death prior to age 55 years in father or other male 1st-degree relative,
or before age 65 years in mother or other female 1st-degree relative)
B79
1 LIPID PROFILE (CONT’D)

Dyslipidemia Screening (Cont’d)
• Women should be screened in the same way as men
Young Adults (Men 20-45 Years of Age; Women 20-55 Years of Age)
• The U.S. Preventive Services Task Force recommends screening for lipid disorders in men ≥35 years old &
women ≥45 years old if the latter is at increased risk of CHD
• Evaluate for dyslipidemia every 5 years
Middle-aged Adults (Men 45-65 Years of Age; Women 55-65 Years of Age)
• Evaluate at least every 1-2 years in the absence of CVD risk factors
• Evaluate more frequently in the presence of multiple global CVD risk factors
Adults >65 Years of Age
• Evaluate annually those w/ 0-1 CVD risk factor
Adult w/ Diabetes Mellitus (DM)
• All adult patients w/ DM should be screened annually for dyslipidemia
Pediatric Screening
• Children >2 years of age should be screened every 3-5 years if they have CVD risk factors, family history of
dyslipidemia or premature CVD, obese or overweight, have other elements of insulin resistance syndrome, or
have no available family history
• Adolescents >16 years of age should be screened every 5 years
• If w/ CVD risk factors, w/ family history of dyslipidemia or premature CVD, obese or overweight, or w/ other
elements of insulin resistance syndrome, screen patient more frequently
Dyslipidemia Screening Tests
Fasting Lipid Profile
• Used to ensure that the most accurate lipid assessment is achieved
- For lipid screening, both fasting & non-fasting specimens may be utilized
• Includes plasma or serum TC, LDL-C, HDL-C & TG
LDL-C
• Recommended as the primary lipid analysis method for screening, diagnosis & management of dyslipidemia
• Direct measurement of LDL-C in certain high-risk patients (eg patients w/ DM, vascular disease, fasting TG
level >2.9 mmol/L or >250 mg/dL) is recommended
- Estimation by Friedewald equation is valid only for values obtained in the fasting state, & is largely inaccurate
in TG levels >2.3 mmol/L (>200 mg/dL) & is invalid when TG levels are 4.5 mmol/L (>400 mg/dL)
HDL-C
• HDL-C >1.6 mmol/L (>60 mg/dL) is an independent negative risk factor for dyslipidemia in both sexes
• In women, very low HDL-C (<1.03 mmol/L or <40 mg/dL) is an independent risk factor for development of CVD
& mortality, even in the presence of normal LDL-C &/or TG levels or TC level <5.2 mmol/L (<200 mg/dL)
- Women w/ low HDL-C have a CVD risk elevated to almost 3-fold (as compared w/ women w/ high HDL-C)
• Considered as an alternative risk marker, especially in combined hyperlipidemias, diabetes, metabolic syndrome
or chronic kidney disease
Non-HDL-C (TC minus HDL-C)
• In patients w/ moderately increased TG (2.3-5.6 mmol/L or 200-500 mg/dL), DM &/or established CVD, or
DYSLIPIDEMIA
if insulin resistance is suspected, measure non-HDL-C

• Provides a better risk assessment than LDL-C alone in patients w/ moderately elevated TG
• Shows the total atherogenic burden including particles contained within VLDL, intermediate-density lipoproteins
(IDL), LDL, chylomicron remnants & lipoprotein(a) [Lp(a)]
• Can be considered as an additional therapeutic target for residual CV risk reduction after the LDL-C has been
reached
Triglycerides
• TG levels ≥1.7 mmol/L (≥150 mg/dL) may help identify those at risk for insulin resistance syndrome
• TG levels ≥2.3 mmol/L (≥200 mg/dL)may point to a significant increase in the risk for CVD
• Very high TG level is associated w/ increased risk of pancreatitis
Apolipoprotein B
• Target apo B level to <90 mg/dL (<0.9 g/L) for those at risk of CVD (including those w/ DM)
• Target apo B level to <80 mg/dL (<0.8 g/L) for those w/ established CVD or those w/ DM who have ≥1 additional
risk factors
• May help evaluate the success of LDL-C lowering therapy
• Can be considered as an additional therapeutic target to further reduce CV event in individuals on statin
therapy who have achieved their LDL-C goal
• Recommended for risk assessment in patients w/ high TG levels, DM, obesity, metabolic syndrome or very
low LDL-C levels
- Considered as an alternative risk marker, especially in combined hyperlipidemias, diabetes, metabolic
syndrome or chronic kidney disease (CKD)
B80
1 LIPID PROFILE (CONT’D)

Dyslipidemia Screening Tests (Cont’d)
Apolipoprotein B (Cont’d)
• Apo B &/or Apo B/Apo A1 ratio calculation & evaluation in patients w/ TG ≥150, HDL-C <40, prior ASCVD event,
T2DM, &/or insulin resistance syndrome may help in determining the best treatment strategy
• Apo B reflects LDL particle number & is considered a more potent measure of CVD risk as compared w/
LDL-C & LDL particle size
• Measurement of Apo B-100 provides a more accurate evaluation of atherogenicity since all atherogenic particles
(VLDL, IDL, LDL) contain 1 Apo B-100 molecule
Lipoprotein(a) [Lp(a)]
• A LDL particle w/ an Apo(a) moeity that has pro-atherogenic effects attributed to its pro-coagulant &
pro-inflammatory effects
• Should be measured at least once in a person’s lifetime to identify people who have inherited an elevated Lp(a)
level of ≥430 nmol/L (≥180 mg/dL) & have a very high lifetime risk of ASCVD
• Should be considered in patients w/ an estimated 10-year risk of ASCVD that is near the threshold between
high & moderate risk
• Evaluation of lipid profile must be performed in parallel w/ risk assessment for CVD
- LDL-C is used as primary lipid analysis for screening & risk estimation
• Risk assessment tools [eg Framingham risk score, Reynold’s risk score, Systemic Coronary Risk Estimation
(SCORE), Risk Factor Counting, Multi-Ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk w/
coronary artery calcification calculator, United Kingdom Prospective Diabetes Study (UKPDS) risk engine in
individuals w/ T2DM, etc] are commonly used to assess a patient’s risk for CVD
- Point system for CVD risk differs by gender
- Framingham risk score:
- Predictors include age, sex, smoker/non-smoker, TC & HDL cholesterol levels, systolic BP & if the patient
is being treated w/ antihypertensive drugs
- High systolic BP, age, TC & smoking are more significant in women
- 130-139 mmHg systolic BP has more points in women (untreated - 2; treated - 4) than in men (untreated - 1;
treated - 2) but overall points have lower threshold for men than in women (10 total points = 6% 10-year risk
in men vs 1% in women)
- ASCVD risk assessment is not necessary in secondary prevention, in individuals w/ LDL-C ≥190 mg/dL, or
in those 40-75 years old w/ DM
- SCORE can be used in different populations when recalibrated by adjusting for secular changes in CVD
mortality & risk factor prevalence
- In the Philippines, Risk Factor Counting is used as the method of identifying the risk of the Filipino individual
for CVD; statin therapy can be considered for primary prevention in individuals without diabetes aged ≥45
years old w/ LDL-C ≥130 mg/dL & at least ≥2 risk factors
• Identify patients w/ established CVD or w/ CVD risk equivalents: DM, PAD or abdominal aortic aneurysm
• Major independent risk factors for CVD
- Cigarette smoking - Age (men ≥45 years; women ≥55 years) DYSLIPIDEMIA
- Low HDL cholesterol (<40 mg/dL) - CKD stage 3/4
- Increased total serum cholesterol level - Increased LDL-cholesterol levels (≥190 mg/dL)
- Increased non-HDL-cholesterol levels
- Hypertension (elevated BP or on antihypertensive medication)
- History of preeclampsia or pregnancy-induced hypertension in women
- Family history of premature ASCVD (male 1st-degree relative <55 years; female 1st-degree relative <65 years)
- Diabetes mellitus
- For individuals w/ high HDL cholesterol 1.5 mmol/L (>60 mg/dL), subtract 1 risk factor from the total
- History of gestational diabetes in women
• Additional risk factors
- Dyslipidemic triad (hypertriglyceridemia, low HDL-C & excess of small, dense LDL)
- Obesity, abdominal obesity - Family history of hyperlipidemia
- Elevated apo B - Polycystic ovarian syndrome (PCOS) in women
- Elevated LDL particle number - Elevated small, dense LDL-C
- Fasting/postprandial hypertriglyceridemia - Microalbuminuria/proteinuria
- History of premature menopause - South Asian ancestry
• Nontraditional risk factors
- Elevated lipoprotein (a) - Elevated homocysteine levels
- Elevated clotting factors - Apo E4 isoform
- Elevated inflammation markers - Elevated uric acid
- Elevated triglyceride-rich remnants
B81
2 RISK STRATIFICATION (CONT’D)
CVD RISK CATEGORIES

ACC/AHA 2019 ESC 2021
Risk
Category 10-Year ASCVD Apparently Healthy Patients w/ Risk Factors
Risk1 Individuals2
Very High No • < 50 years: ≥7.5% • D ocumented clinical ASCVD [eg previous
Risk recommendation • 50-69 years: ≥10% acute myocardial infarction (AMI), acute
• ≥70 years: ≥15% coronary syndrome (ACS), coronary
revascularization & other arterial
revascularization procedures, TIA & stroke,
aortic aneurysm & PAD] or unequivocally
documented ASCVD finding (eg significant
plaque) on imaging that does not include
some increase in continuous imaging
parameters (eg intima-media thickness of
the carotid artery)
• T2DM w/ established ASCVD &/or severe
target organ damage (TOD)3
• Without diabetes or ASCVD but w/ severe
CKD [estimated glomerular filtration rate
(eGFR) <30 mL/min/1.73 m2] or eGFR 30-44
mL/min/1.73 m2 & albumin-to-creatinine
ratio (ACR) >30
High Risk ≥20% • < 50 years: 2.5-<7.5% • T 2DM without ASCVD &/or severe TOD w/
• 50-69 years: 5-<10% moderate risk criteria not met3
• ≥70 years: 7.5-<15% • Without diabetes or ASCVD but w/ moderate
CKD (eGFR 30-44 mL/min/1.73 m2) & ACR
<30 or eGFR 45-59 mL/min/1.73 m2 & ACR
30-300 or eGFR ≥60 mL/min/1.73 m2 & ACR
>300
• Familial hypercholesterolemia associated w/
markedly increased levels of cholesterol
Moderate No • < 50 years: <2.5% • P
atients w/ <10 years of well-controlled
Risk recommendation • 50-69 years: <5% T2DM without TOD or other ASCVD risk
• ≥70 years: <7.5% factors3
Intermediate 7.5% to <20% No recommendation
Risk
Borderline 5% to <7.5% No recommendation
Risk
Low Risk <5% • < 50 years: <2.5%
DYSLIPIDEMIA
• 50-69 years: <5%

• ≥70 years: <7.5%
1ASCVD risk estimator (http://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calculate/estimator/)
estimates the 10-year ASCVD risk for asymptomatic individuals 40-75 years old.
2Based on SCORE2 & SCORE2-Older Persons (SCORE2-OP)
SCORE2 estimates the 10-year risk of fatal & non-fatal CVD events (eg stroke, MI) in apparently healthy
individuals 40-69 years old w/ risk factors that are not treated or have been stable for several years; can be
accessed in the ESC CVD Risk Calculation app.
SCORE2-OP estimates the 5- & 10-year fatal & non-fatal CVD events (eg stroke, MI) adjusted for
competing risks in apparently healthy individuals ≥70 years old.
3Patients >40 years old w/ type 1 DM may also be classified according to these criteria.
References:
• Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the primary prevention of
cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. Circulation. 2019.
• Visseren FLJ, Mach F, Smulders YM, et al; ESC National Cardiac Societies, ESC Scientific Document
Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021.
B82
3 EVALUATION
• Relative reduction of risk is proportional to the absolute LDL-C reduction & the absolute LDL-C reduction
resulting from a particular drug regimen depends only on baseline LDL-C, at any given level of baseline risk
the higher the initial LDL-C level the greater the absolute reduction in risk
CVD Risk Category Untreated LDL-C Levels That Warrant Drug Therapy
Very High Risk >1.4 mmol/L (>55 mg/dL)
High Risk >1.8 mmol/L (>70 mg/dL)
Moderate Risk >2.6 mmol/L (>100 mg/dL)
Low Risk >3 mmol/L (>116 mg/dL)
Reference: Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of
dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020.
4 LIPID TREATMENT GOALS

• Targeted approach to lipid management is primarily aimed at reducing atherosclerotic risk by substantially
lowering LDL-C levels
• Currently, no specific treatment goals for HDL-C or TG levels have been established in clinical trials
LIPID TREATMENT GOALS BASED ON CVD RISK

Risk Category LDL - C Non-HDL-C Apo B
Very High Risk <1.4 mmol/L <2.2 mmol/L <1.6 mmol/L
(<55 mg/dL) (<85 mg/dL) (<65 mg/dL)
High Risk <1.8 mmol/L <2.6 mmol/L <2 mmol/L
(<70 mg/dL) (<100 mg/dL) (<80 mg/dL)
Moderate Risk <2.6 mmol/L <3.4 mmol/L <2.6 mmol/L
(<100 mg/dL) (<130 mg/dL) (<100 mg/dL)
Low Risk <3 mmol/L - -
(<116 mg/dL)
Reference: Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid
modification to reduce cardiovascular risk. Eur Heart J. 2020.
A LIFESTYLE MODIFICATIONS
• Patients w/ dyslipidemia are advised to have lifestyle modification regardless of their risk profile DYSLIPIDEMIA
- ASCVD risk is reduced by a healthy lifestyle in all age groups
Dietary Recommendations
• Recommended LDL-C-lowering diet:
- Increase vegetables, fruits, whole grain products, low-fat dairy products, poultry, fish, legumes, non-tropical
vegetable oil, & nuts
- Limit red meat, sweetened beverages, chocolates & sweets
• Dietary fat should range from 20-30% of total calories
- Saturated fat should be <10% of total calories
- Cholesterol should be <300 mg/day
- Polyunsaturated fat can be up to 6-10% of total calories
- Monounsaturated fats: Total Fats - (Saturated + Polyunsaturated fats)
- May comprise up to 20% of caloric intake
- Reducing trans fat (<1% of total calories) may decrease LDL-C
• Reduce sodium consumption to ≤2,400 mg/day
- Decreasing sodium intake to 1,150 mg/day may reduce BP in 30- to 80-year-old patients w/ or without
hypertension by up to 4/2 mmHg
- When reduced to 1,000 mg/day, studies showed decrease in CVD events by 30%
B83
A LIFESTYLE MODIFICATIONS (CONT’D)

Dietary Recommendations (Cont’d)
• Carbohydrates should range from 45-55% of total energy intake
- Lower carbohydrate intake if w/ high TG & low HDL-C
- Source of carbohydrates should be mainly from complex carbohydrates
- Includes grains (especially whole grains), fruits & vegetables
• Fiber: 25-40 g/day of total dietary fiber
• Protein should be 15-20% of total calories
• Total calories should be enough to balance energy intake & expenditure to maintain body mass index (BMI)
for Asian adults of 18.5-23 kg/m2 or BMI for European adults of 20-25 kg/m2
• Moderate intake of fatty fish that is boiled, broiled or baked but not fried
- Up to 2 servings of fatty fish per week for the general population is recommended while CAD patients should
consume 1 g of eicosapentaenoic acid (EPA) & docosahexaenoic acid (DHA) through fatty fish or high-quality
dietary supplements
- Omega-3 fish oil supplements may be considered to treat severe hypertriglyceridemia (TG >500 mg/dL) &
for secondary prevention of CVD
Increase Physical Activity
• Physical activity can reduce risk for CVD
• Reduce sedentary time
• Moderate aerobic exercise (eg brisk walking, swimming, jogging, cycling) 3-4x/week (ideally daily) for 30-40
minutes at each session is recommended
• Aerobics may reduce LDL-C levels in adults by 3-6 mg/dL & non-HDL-C by 6 mg/dL
• Studies show that resistance training helps lower LDL-C, TG & non-HDL-C levels by 6-9 mg/dL
• Especially helpful in patients w/ metabolic syndrome
• Muscle-strengthening exercise is recommended ≥2 days/week in addition to aerobic exercises
- Studies have shown that weight & resistance training may benefit patients w/ insulin resistance syndrome
regardless of body fat or aerobic fitness
Weight Loss
• Achieved mainly by dietary changes & exercise
• Weight loss should be gradual
- 10% of body weight in 6 months
• Waist circumference maintained at <90 cm for men & <80 cm for women
Moderate Alcohol Intake
• ≤2 drinks/day (up to 20 g/day) for men
• ≤1 drink/day (up to 10 g/day) for women
Smoking Cessation
• Patient must quit immediately
• Has beneficial effect on overall CV risk & specifically on HDL-C levels
Intensifying Lifestyle Modifications
DYSLIPIDEMIA
Increasing Viscous Fiber

• Therapeutic option to help lower LDL-C
• Viscous (soluble) fiber is found in oats, pectin-rich fruit, barley, psyllium, beans, etc
- 5-10 g/day can reduce LDL-C levels by ~5%
Plant Stanols/Sterols
• Sterols are isolated from soybean & tall pine tree oils
• Lipids are needed to solubilize stanol/sterol esters
- Found in commercial margarines, where available
• 2g/day lower TC & LDL-C by 7-10%
• Help reduce cholesterol absorption
Referral to Dietitian
• Consultation w/ qualified professional for medical nutrition therapy
• List foods rich in omega-3 fatty acids EPA & DHA
B84
B LDL-C-LOWERING PHARMACOLOGICAL THERAPY

LDL-C is the primary target of lipid management
• The greater the LDL-C level is reduced, the more significant is the amount of CV risk reduction
• Assess patient’s response to LDL-C-lowering therapy & lifestyle modifications w/ a repeat lipid profile 4-12
weeks after starting statin therapy or dose adjustment then every 3-12 months as needed
Statins [Beta-hydroxy-beta-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Inhibitors]
• Reduce risk for ACS, coronary procedures & other coronary outcomes in both primary & secondary CHD
prevention
• Recommended for the following:
- Adults ≥21 years old w/ clinical ASCVD
- Adults ≥21 years old w/ LDL-C ≥190 mg/dL
- Adults 40-75 years of age without ASCVD but w/ DM (especially T2DM) & LDL-C levels of 70-189 mg/dL
- Adults 40-75 years of age without ASCVD & DM but w/ LDL-C levels of 70-189 mg/dL & estimated 10-year
risk of ≥7.5% for ASCVD
- If decision to start statin therapy is uncertain, measure coronary artery calcium (CAC); statin therapy is
favored w/ a CAC score of 1-99 & is indicated w/ a CAC score of ≥100 Agatston units or ≥75th percentile
- Adults 40-75 years of age without DM but w/ risk-enhancing factors & estimated 10-year ASCVD risk of
7.5-19.9%
• Effective in patients w/ nephrotic syndrome
• Inhibit HMG-CoA reductase which is the rate-limiting step in cholesterol biosynthesis
• Most effective class of drugs at lowering LDL-C levels, w/ moderate effects on lowering TG & elevating HDL-C:
Decreases LDL-C in a dose-dependent manner by 20-55%, decreases TG by up to 35%, increases HDL-C by
2-10%
• The drugs of choice for LDL lowering & in reducing CVD risk in high-risk patients (eg DM) w/
hypertriglyceridemia
- Statin dose may be increased or non-statin drug (eg Ezetimibe, fibrates, or Nicotinic acid) may be added if
TG levels remain at >2 mmol/L (>200 mg/dL) after achieving the LDL-C target level
• High-intensity statins: Atorvastatin (80 mg), Rosuvastatin (20 mg)
- Statin regimen that helps lower LDL-C by ≥50%
- Recommended to be given at the highest tolerated dose to achieve the LDL-C goals set for a specific risk
group
- Recommended as 1st-line treatment for patients <75 years old w/ clinical ASCVD
- May be used for patients ≥21 years old w/ LDL-C ≥190 mg/dL or TG ≥500 mg/dL especially those trying to
achieve at least 50% LDL-C level reduction
- A non-statin drug may be added if LDL-C goal has not been achieved w/ high-intensity regimen
- For ≥75-year-old patients w/ ASCVD, without contraindications
- For 40-75-year-old patients w/ DM w/ ≥7.5% 10-year ASCVD risk1
- For 40-75-year-old patients w/ DM or LDL-C ≥190 mg/dL
• Moderate-intensity statins: Atorvastatin (10 mg), Rosuvastatin (10 mg), Simvastatin (20-40 mg), Pravastatin
(40 mg), Lovastatin (40 mg), Fluvastatin (40 mg 12 hourly), Pitavastatin (1-4 mg) DYSLIPIDEMIA
- Daily dose helps lower LDL-C by 30-49%
- Alternative treatment for patients w/ clinical ASCVD w/ contraindications against high-intensity statins or
w/ side effects from statin therapy
- For ≥75-year-old patients w/ ASCVD, w/ contraindications/intolerance to high-intensity statins
- For 40-75-year-old patients w/ DM w/ or without 5-≤7.5% 10-year ASCVD risk
- For 40-75-year-old patients w/ DM & LDL-C 70-189 mg/dL
- For 40-75-year-old patients w/ DM or LDL-C ≥190 mg/dL w/ contraindications/intolerance to high-intensity statins
- For 40-75-year-old patients without DM but LDL-C ≥70 mg/dL & ≥7.5% 10-year ASCVD risk
• Low-intensity statins: Simvastatin (10 mg), Pravastatin (10-20 mg), Lovastatin (20 mg), Fluvastatin (20-40 mg)
- Daily dose helps lower LDL-C by <30%
• Treatment w/ statin is associated w/ the risk of developing statin-associated muscle symptoms (SAMS) or
new-onset DM but benefits of statin therapy for CV risk reduction outweigh the risk
1Riskof developing a first ASCVD event, defined as nonfatal myocardial infarction or CHD death or fatal or nonfatal stroke, over a
10-year period among people free from ASCVD at the beginning of the period.
B85
B LDL-C-LOWERING PHARMACOLOGICAL THERAPY (CONT’D)

Selective Cholesterol-Absorption Inhibitor
• Eg Ezetimibe
• 1st optional non-statin to consider for patients w/ poor tolerance to statins
• 1st option to add onto maximally tolerated statin therapy in patients who are less responsive to statins & failed
to reach LDL-C goals
- May be added to a maximally tolerated statin therapy in patients w/ very high-risk ASCVD when LDL-C
level remains ≥70 mg/dL
- Combination is a strategy to prevent side effects associated w/ statin monotherapy
- Combination products of selective cholesterol-absorption inhibitor + statin, eg Ezetimibe/Simvastatin,
Ezetimibe/Atorvastatin, are available & may be used to reduce LDL-C, apo B, TG & non-HDL-C & to increase
HDL-C
- The IMPROVE-IT trial in patients w/ recent ACS showed further decrease in LDL-C & reduction in
cardiovascular events w/ the addition of Ezetimibe to a moderate-intensity statin (Simvastatin) over 6 years
of follow-up
- The SHARP trial demonstrated reductions in LDL-C & primary endpoint of 1st major ASCVD event w/
Ezetimibe plus Simvastatin when compared to placebo over 4.9 years of follow-up
- If the addition of Ezetimibe to a statin achieved therapy goals, the combination therapy may be continued
w/ continuous monitoring of treatment response
• Beneficial in patients w/ homozygous familial hypercholesterolemia
• Ezetimibe/statin combination is recommended in patients w/ CKD stage 3-5 not dependent on dialysis
• Selective potent inhibitor of cholesterol absorption in the intestinal lumen & reduces the overall delivery of
cholesterol to the liver
• Causes moderate reduction in LDL-C levels
- When used alone, Ezetimibe decreases LDL by 10-20% w/ favorable effects on HDL & TG
- When used in combination w/ statins, there is an additional reduction in LDL-C by 18-25% w/ favorable
effects on HDL & TG, w/ Fenofibrate 20-22% reduction in LDL-C
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors
• Eg Alirocumab, Evolocumab
• As human monoclonal PCSK9 antibody, it binds to PCSK9 which then increases LDL receptor density
• May be given alone or in combination w/ a maximally tolerated statin dose &/or other lipid-lowering therapies,
eg Ezetimibe
• Recommended as adjunct to diet & maximally tolerated statin therapy plus Ezetimibe for the treatment of
heterozygous familial hypercholesterolemia w/ very high risk or clinical ASCVD that needs further reduction
of LDL-C
• Given also to patients w/ very high & high CV risk w/ intolerance to statin therapy
• Addition of a PCSK9 inhibitor is recommended to patients w/ very high-risk ASCVD or severe primary
hypercholesterolemia w/ multiple risk factors for ASCVD events if the LDL-C level remains above goal on
maximally tolerated statin & Ezetimibe therapy
• Addition of a PCSK9 inhibitor is also recommended in patient w/ ACS whose LDL-C goal is not achieved after
4-6 weeks of maximal tolerated statin therapy plus Ezetimibe
• Evolocumab may also be given in combination w/ other LDL-lowering agents (eg statins, Ezetimibe, LDL
apheresis) to treat homozygous familial hypercholesterolemia needing further reduction of LDL-C
• Lowers LDL-C levels by 48-71%, TC by 36-42%, apo B by 42-55%, & non-HDL-C by 49-58%
Anti-sense Apolipoprotein B Oligonucleotide
• Eg Mipomersen
• May be used for patients w/ homozygous familial hypercholesterolemia unresponsive to PCSK9 inhibitor
DYSLIPIDEMIA
therapy; may also be considered in patients w/ ASCVD & baseline LDL-C ≥190 mg/dL who had inadequate
response to statin therapy (w/ or without Ezetimibe & PCSK9 inhibitors)
• Hybridization to mRNA results to RNase H-mediated degradation of mRNA used for translation of apo B-100
• Lowers LDL-C levels by 21%, TC by 19%, apo B by 24%, & non-HDL-C by 22%
Bempedoic Acid
• Indicated for the treatment of adults w/ heterozygous familial hypercholesterolemia or established ASCVD
who require additional lowering of LDL-C
• Lowers LDL-C by inhibiting action of adenosine triphosphate-citrate lyase, which is an enzyme that works
upstream of HMG-CoA reductase
• May be used alone or in combination w/ statins & Ezetimibe
- Has been shown to decrease LDL-C by 15-24% & in combination w/ Ezetimibe by 36% in clinical trials
Bile Acid Sequestrants
• Have been shown to reduce risk for CVD; considered in patients who have contraindications or intolerance
to statin therapy
• Also effective in LDL lowering in patients w/ DM
• Bind bile acids in the intestine through anion exchange
• Cause moderate reduction in LDL-C levels
- LDL-lowering potential increases when combined w/ other agents (eg statins)
- May raise TG levels in some patients
- Decrease LDL-C by 15-25%; increase HDL-C by 4-11%
B86
B LDL-C-LOWERING PHARMACOLOGICAL THERAPY (CONT’D)

Evinacumab
• An add-on treatment for patients ≥12 years old w/ homozygous familial hypercholesterolemia
• A fully human monoclonal antibody that binds to angiopoietin-like protein 3 (ANGPTL3) which in turn
inhibits lipoprotein & endothelial lipase
• A clinical trial showed a significant reduction in LDL-C when given subcutaneously or intravenously to patients
w/ refractory hypercholesterolemia despite maximal doses of statin (w/ or without Ezetimibe) & a PCSK9 inhibitor
Inclisiran
• Indicated for the treatment of adults w/ primary hypercholesterolemia (heterozygous familial & non-familial)
or mixed dyslipidemia, or clinical ASCVD requiring additional lowering of LDL-C
• Given as an adjunct to diet in combination w/ a statin or statin w/ other lipid-lowering therapies in patients
unable to reach LDL-C goals w/ max tolerated statin dose; or alone or in combination w/ other lipid-lowering
therapies in patients who are statin intolerant or for whom a statin is contraindicated
• It is a small-interfering RNA LDL-C lowering treatment that targets hepatic PCSK9 synthesis
• Dosing regimen is infrequent (initial dose is given subcutaneously which is repeated at 3 months then every
6 months) & side effects are acceptable
Microsomal Triglyceride Transfer Protein (MTP) Inhibitor
• Eg Lomitapide
• May be used for patients w/ homozygous familial hypercholesterolemia unresponsive to PCSK9 inhibitor
therapy; may also be considered in patients w/ ASCVD & baseline LDL-C ≥190 mg/dL who had inadequate
response to statin therapy (w/ or without Ezetimibe & PCSK9 inhibitors)
• Inhibits chylomicron & VLDL synthesis by direct binding & inhibition of MTP
• Lowers LDL-C levels by 40%, TC by 36%, apo B by 39%, TG by 45%, & non-HDL-C by 40%
Nicotinic Acid
• Favorably affects all lipid & lipoproteins when given in the proper dosage
- Lower doses increase HDL-C
- 2-3 g/day are needed to lower LDL-C
• Moderate reduction in CVD risk
• Alter lipid levels by inhibiting lipoprotein synthesis & decreasing the production of VLDL particles by the liver
• Most effective at raising HDL levels among lipid-modifying drugs
- Decrease LDL-C by 5-25%
- Increase HDL-C by 10-35%
- Decrease TG by 20- 30% in a dose-dependent manner
• May be combined w/ statins in managing DM patients w/ hypertriglyceridemia
• May increase blood glucose levels
Intensified LDL-C-Lowering Pharmacotherapy
• Dose increase
• Combination therapy eg statin w/ Ezetimibe w/ or without a PCSK9 inhibitor, statin w/ PCSK9 inhibitor,
Ezetimibe w/ PCSK9 inhibitor, statin w/ bile acid sequestrant
C TG-LOWERING & HDL-C-RAISING PHARMACOLOGICAL THERAPY

Fibrates
• Primary use is for lowering TG
- Decrease TG by 20-50% DYSLIPIDEMIA
- May be combined w/ statins in managing DM patients w/ hypertriglyceridemia & low HDL-C
- If TG is not elevated, fibrates may lower LDL-C by 5-20%
• Also useful in combined/mixed dyslipidemia & in increasing HDL-C by 6-35%
• Recommended for patients w/ very high TG (>4.5 mmol/L) who are at risk for pancreatitis
• Moderately reduce risk for CHD
• Favorably lower LDL in patients w/ DM
• Down-regulate the apolipoprotein C-III (apoC-III) gene & up-regulate genes for apolipoprotein A-1, fatty acid
transport protein, fatty acid oxidation & possibly lipoprotein lipase
• Primarily target atherogenic dyslipidemia including diabetic dyslipidemia
- Fenofibrate w/ or without statin therapy reduces progression of diabetic retinopathy
• When used in combination w/ LDL-lowering drugs, it improved the overall lipoprotein compared to either
agent alone
- In combination w/ statin, Fenofibrate is the preferred fibrate to use due to lower risk of myopathy &
rhabdomyolysis
• Provide an alternative treatment in statin-intolerant patients w/ mild to moderate hypercholesterolemia
• In patients in whom a fibrate is recommended, Nicotinic acid can also be considered
• Pemafibrate is a novel selective peroxisome proliferator-activated receptor alpha (PPARα) modulator w/ a
favorable benefit-risk balance compared to conventional fibrates
- May be used to treat patients w/ hypertriglyceridemia & to prevent CV events in those w/ hypertriglyceridemia
Nicotinic Acid
• Please see discussion under LDL-C-Lowering Pharmacological Therapy
B87
C TG-LOWERING & HDL-C-RAISING PHARMACOLOGICAL THERAPY (CONT’D)

Omega-3 Fatty Acids
• Total EPA & DHA at dosages between 2 to 4 g/day can lower serum TG levels
- Studies showed EPA reduced serum TG levels by up to 45% in a dose-dependent manner
• Icosapent ethyl (IPE) is a highly purified, non-oxidized form of EPA & is indicated for patients w/ TG levels
≥150 mg/dL w/ established ASCVD or diabetes w/ ≥2 ASCVD risk factors & on maximally tolerated statins
to prevent ASCVD morbidity & mortality
Volanesorsen
• Clinical trials have shown its efficacy in the treatment of patients w/ elevated TG & familial chylomicronemia
syndrome (FCS)
- Given to adult patients w/ FCS & at high risk for pancreatitis w/ inadequate response to a low-fat diet &
TG-lowering therapy
• An antisense oligonucleotide that binds to apoC-III mRNA & prevents translation of apoC-III allowing for
the metabolism & breakdown of TG & chylomicrons
TREATMENT OF SPECIFIC DYSLIPIDEMIAS

Very High LDL Cholesterol [≥4.9 mmol/L (≥190 mg/dL)]
• Usually caused by genetic forms of hypercholesterolemia
• For patients at very high risk & w/ persistent high risk, use a maximally tolerated statin &, if necessary, Ezetimibe
to lower LDL-C levels; if still not at treatment goal, a PCSK9 inhibitor may be added
• May consider addition of a bile acid sequestrant in patients 20-75 years old w/ an LDL-C level of ≥4.9 mmol/L
(≥190 mg/dL) w/ <50% reduction in LDL-C & TG ≤3.4 mmol/L (≤300 mg/dL) while on maximally tolerated
statin & Ezetimibe therapy
Elevated TG
• Strong association between high TG levels & CHD risk
• TG levels ≥2.3 mmol/L (≥200 mg/dL) indicate the need to identify non-HDL-C level, which is the secondary
target of lipid-lowering therapy in these patients (LDL-C is still the primary goal of therapy)
- Non-HDL-C is more representative of all atherogenic lipoproteins than LDL-C
- Non-HDL-C (mmol/L) = TC-HDL-C; non-HDL-C levels can be calculated from non-fasting serum
• Acquired causes: Obesity, physical inactivity, excess alcohol intake, high carbohydrate diet
- Secondary causes (eg DM, CRF, nephrotic syndrome, chronic liver disease, hypothyroidism, Cushing’s disease,
various medications, etc)
- Genetic causes
• Elevated TG can often be effectively treated through lifestyle changes; however, fibrates, Niacin, & combination
therapy w/ statins may be appropriate options for many patients
• Very high TG [>5.6 mmol/L (≥500 mg/dL)]
- Treatment should be likened to an emergency to avoid acute pancreatitis
- Fibrate (preferably Fenofibrate), prescription omega-3 fatty acids, or Nicotinic acid should be started
- Lifestyle modifications
- Fish oils can replace some long-chain TG in diet
• If LDL-C is still elevated despite a fibrate, consider adding a statin
- Decision must be individualized
- Must be started only when it is strongly indicated
- The recommended fibrate to be combined w/ a statin is Fenofibrate
DYSLIPIDEMIA
• High TG [2.3-5.6 mmol/L (200-499 mg/dL)]

- If LDL-C or non-HDL-C levels are high or ASCVD risk ≥5%: Start statin
- Consider combination therapy w/ Fenofibrate if LDL-C is at goal but TG level remains >200 mg/dL in
primary prevention or high-risk patients
- Consider combination therapy w/ IPE if TG level is between 135-499 mg/dL despite statin therapy in
patients at high risk (or above)
• Borderline high TG [1.7-2.2 mmol/L (150-199 mg/dL)]
- Medications are rarely required unless LDL-C is elevated above target level
Low HDL-C [<1 mmol/L (<40 mg/dL)]
• Low HDL-C is a strong, independent predictor of CHD
• Excluding secondary causes of low HDL-C & in the presence of other risk factors (eg borderline LDL-C,
personal history of CAD, or a family history of premature CAD), HDL-C levels should be raised by as much
as possible to levels of at least >40 mg/dL in both men & women
• Raising HDL-C levels alone in patients without accompanying risk factors is not recommended
Low HDL-C without Hypertriglyceridemia
• Causes: Obesity, physical inactivity, cigarette smoking, T2DM, certain drugs, etc
• Treatment in patients w/ CHD or CHD-risk equivalents when lifestyle modifications fail to increase HDL
include fibrates or Nicotinic acid
B88
TREATMENT OF SPECIFIC DYSLIPIDEMIAS (CONT’D)

Low HDL-C w/ Hypertriglyceridemia
• HDL-C is low & TG is high & LDL-C is not significantly elevated: Start fibrates or Nicotinic acid
Elevated Lipoprotein(a)
• Aggressive reduction of LDL-C will help lower Lp(a)
• Agents that have shown to reduce Lp(a) by approximately 20-30% include high-dose Niacin, PCSK9 inhibitors,
Estrogen & Aspirin
- Niacin reduces Lp(a) by an average of 25% & may be given to patients w/ elevated Lp(a) & hypercholesterolemia
w/ elevated LDL-C despite maximum tolerated statin therapy & Ezetimibe
Atherogenic Dyslipidemia [TG ≥1.7 mmol/L (≥150 mg/dL) & HDL-C <1 mmol/L (<40 mg/dL)]
• The patient likely has metabolic syndrome
• Attempt adequate trial of lifestyle modification to meet LDL-C goals
- Add LDL-lowering drug therapy if lifestyle modification fails to reach LDL-C goals
• TG <2.3 mmol/L (<200 mg/dL): Drug therapy to lower TG is not necessary
- If patient has CHD or CHD risk equivalents, consider using drug therapy to raise HDL-C (eg fibrates or
Nicotinic acid)
• TG 2.3-5.7 mmol/L (200-499 mg/dL): If non-HDL-C remains elevated after adequate LDL-C lowering therapy:
May consider higher dose of statin or statin + TG-lowering drug (fibrate or Nicotinic acid)
Apolipoproteins
• Target apo B level at <90 mg/dL for patients at risk of CAD, including those w/ DM
• Target apo B level at <80 mg/dL for patients w/ established CAD or DM plus ≥1 additional risk factor
Familial Hypercholesterolemia
• Common autosomal dominant genetic disease that causes LDL-C level elevation
• Causes early-onset CHD
• Dutch Lipid Clinic Network criteria are used for the diagnosis of heterozygous familial hypercholesterolemia
in adults & include the following:
- Family history
- 1st-degree relative w/ known premature* coronary or vascular disease, or 1st-degree relative w/ known
LDL-C >95th percentile = 1 point
- 1st-degree relative w/ tendinous xanthomata &/or arcus cornealis, or children <18 years old w/ LDL-C
>95th percentile = 2 points
- Clinical history
- Premature* coronary artery disease = 2 points
- Premature* cerebral or peripheral vascular disease = 1 point
- Physical examination
- Presence of tendinous xanthomata = 6 points
- Presence of arcus cornealis before 45 years old = 4 points
- LDL-C levels (without treatment)
- LDL-C ≥8.5 mmol/L (≥325 mg/dL) = 8 points
- LDL-C 6.5-8.4 mmol/L (251-325 mg/dL) = 5 points
- LDL-C 5.0-6.4 mmol/L (191-250 mg/dL) = 3 points
- LDL-C 4.0-4.9 mmol/L (155-190 mg/dL) = 1 point
- DNA analysis
- Functional mutation in the LDLR, apoB, or PCSK9 genes = 8 points DYSLIPIDEMIA
- Definite diagnosis of familial hypercholesterolemia can be made if the score is >8 points, probable if 6-8
points, possible if 3-5 points
• Treatment of familial hypercholesterolemia includes the following:
- Lifestyle modification that includes intervention on smoking, diet & physical activity
- Initiation of cholesterol-lowering drugs that include statins (maximal potent dose), Ezetimibe, PCSK9
inhibitors (Alirocumab, Evolocumab), bile acid-binding resins, Bempedoic acid or Evinacumab
Pediatric Dyslipidemia
• Benefits of developing healthy lifestyle habits in children have been recognized
• Recommended 1st-line approach is intensive lifestyle modifications (w/ emphasis on improved dietary intake
& normalization of body weight)
- It is recommended that lifestyle changes in children should be implemented for at least 6-12 months prior
to considering pharmacologic therapy
• Studies have shown that high-fiber, low-fat diets are also beneficial in children by helping reduce cholesterol
levels
- However, monitoring of fat-soluble vitamin status in children on low-fat diet is recommended since this may
reduce absorption of these vitamins
• Avoid high carbohydrate diet in children w/ hypertriglyceridemia
• Smoking cessation should also be implemented
*Premature = <55 years old in men, <60 years old in women
B89
TREATMENT OF SPECIFIC DYSLIPIDEMIAS (CONT’D)

Pediatric Dyslipidemia (Cont’d)
• Fish oil supplements are considered to have significant effects on TG levels in children, especially in those w/
end-stage renal insufficiency
• Dietary supplementation w/ plant stanols & sterols (eg orange juice, yogurt drinks, cereal bars, margarines/
spreads, dietary supplements) may be considered for children w/ severe hypercholesterolemia or those who
are at high risk
- Above supplements may also reduce absorption of fat-soluble vitamins; monitoring of fat-soluble vitamin
status is also recommended
• Pharmacotherapy is generally reserved for those w/ severe dyslipidemia or those w/ genetic lipid disorders
• Other candidates for pharmacotherapy include children & adolescents >8 years of age who satisfy the following
criteria:
- LDL-C level of ≥190 mg/dL or
- LDL-C level of ≥160 mg/dL plus
- Presence of ≥2 CAD risk factors
- Family history of premature CAD (<55 years of age)
- Being overweight or obese, or having other elements of insulin resistance syndrome
- Pediatric diabetic patients w/ LDL level of ≥130 mg/dL
• Pharmacotherapeutic options for pediatric dyslipidemia include the following:
- Based on available evidence, statins are considered safe & effective
- Statin therapy can be initiated at 6-10 years of age for the treatment of children w/ familial
hypercholesterolemia in addition to healthy lifestyle measures
- Pediatric studies have demonstrated 15-20% reductions in LDL-C level w/ bile acid sequestrants
- Cholestyramine is currently approved for hypercholesterolemia in children & should be initiated at <8 g
daily
- Safety & efficacy of Colestipol & Colesevelam have not yet been established in pediatric patients although
Colestipol may be started at <10 g daily while Colesevelam is approved for children ≥8 years of age
- Bile acid sequestrants may lead to folic acid & cholecalciferol depletion; multivitamins should therefore
be used
- Bile acid sequestrants should not be used in children w/ hypertriglyceridemia
- Fibrates may be useful in children w/ severe hypertriglyceridemia & at increased risk of pancreatitis
- Use of fibrates in children or adolescents w/ type I or V hyperlipoproteinemia warrants close
monitoring
- Ezetimibe has only been used in children ≥10 years of age & adolescents w/ homozygous familial
hypercholesterolemia or sitosterolemia
- Experience w/ Niacin therapy in children is limited
METABOLIC SYNDROME
• Non-HDL-C is secondary target of therapy (LDL-C lowering is primary)
Clinical Identification
• Any 3 or more of the following (including those on treatment):
- Increased waist circumference (Asian cut off: ≥80 cm for females; ≥90 cm for males)
- Raised TG level ≥1.7 mmol/L (≥150 mg/dL) or specific treatment for this lipid abnormality
DYSLIPIDEMIA
- Reduced HDL cholesterol <1 mmol/L (<40 mg/dL) in males & <1.3 mmol/L (<50 mg/dL) in females or
specific treatment for this lipid abnormality
- Raised BP (SBP ≥130 mmHg or DBP ≥85 mmHg) or treatment of previously diagnosed hypertension
- Disorders of glycemia:
- T2DM, or
- Impaired glucose tolerance (IGT): Fasting plasma sugar <7 mmol/L (<125 mg/dL) & 2 hours post 75-g
glucose load 7.8-11.1 mmol/L (140- 200 mg/dL), or
- Impaired fasting glucose (IFG): Fasting plasma sugar 6.1-7.0 mmol/L (110-125 mg/dL)
Manage the Underlying Causes
• Obesity & physical activity
- Weight loss & increased physical activity will reduce all of the above risk factors
COVID-19 & LIPID-LOWERING THERAPY

• Current evidence shows that lipid-lowering therapy is safe in patients w/ COVID-19 infection
- Lipid-lowering therapy should be continued in patients w/ confirmed COVID-19 diagnosis & abnormal liver
function tests (LFTs) unless alanine transaminase (ALT) or aspartate transaminase (AST) progressively
increases, a significant drug-drug interaction between the lipid-lowering agents & COVID-19 drugs has
been identified, or patient is critically ill &/or cannot take oral medications
B90
Dosage Guidelines
BILE ACID SEQUESTRANTS

Drug Available Preparation Dosage Remarks
Cholestyramine 4 g/packet bulk powd 4 g mixed in liq PO Adverse Reactions
(Colestyramine) once-6x/day • GI effects (constipation,
May increase the dosage at rarely cause fecal
intervals of not <4 wk impaction, abdominal
Max dose: 24 g/day pain, bloating, flatulence)
Colesevelam 625 mg/tab 1875 mg PO 12 hrly w/ Special Instructions
meals or 3750 mg PO • Administer other
24 hrly in 1-2 divided doses medications at least 1 hr
w/ meals before or 4 hr after bile
Max dose: 4375 mg/day acid sequestrants
In combination w/ statin • To minimize GI effects
w/ or without Ezetimibe: start w/ low dose &
2-5-3.75 g PO 24 hrly increase slowly
Colestipol 5 g/packet bulk powd 5-30 g mixed in liq PO

24 hrly or in divided doses
1 g/tab 2-16 g PO 24 hrly or in
divided doses
FIBRATES
Drug Dosage Remarks
Bezafibrate Regular-release: 200 mg Adverse Reactions
PO 8-12 hrly • GI effects (anorexia, nausea, gastric discomfort); CNS
Extended-release: 400 mg effects (headache, vertigo); Other effects (fatigue, rash)
PO 24 hrly • Myalgia, myopathy, rarely rhabdomyolysis: Occurs more
often when combined w/ statins
Ciprofibrate 100 mg PO 24 hrly • Not recommended in patients w/ severe renal or hepatic
dysfunction, gallstones, hypoalbuminemic states
• Use w/ caution in mild-moderate renal impairment
Choline Primary hyperlipidemia Adverse Reactions
fenofibrate or mixed dyslipidemia • GI effects (constipation, diarrhea, dyspepsia, increased
135 mg PO 24 hrly ALT); CNS effects (headache, dizziness); Resp effects
DYSLIPIDEMIA
Severe (sinusitis, nasopharyngitis, upper resp tract infection);
hypertriglyceridemia Other effects (fatigue, arthralgia, back pain, muscle
Initial dose: 45-135 mg PO spasms, myalgia, pain in extremity)
24 hrly; may adjust dose at Special Instructions
4-8 wk interval • Contraindicated in patients w/ hepatic insufficiency
Max dose: 135 mg PO (including biliary cirrhosis & unexplained persistent liver
24 hrly dysfunction), severe renal insufficiency, gallbladder
Co-administration w/ disease, chronic or acute pancreatitis (except acute
statins for mixed pancreatitis due to severe hypertriglyceridemia)
dyslipidemia • Use w/ caution when used concomitantly w/ statins
135 mg PO 24 hrly • Monitor liver function regularly during therapy
• Discontinue if liver enzyme levels persist >3x ULN

B91
Dosage Guidelines
FIBRATES (CONT’D)
Drug Dosage Remarks
Fenofibrate Regular-release: 100 mg PO 8 hrly w/ Adverse Reactions
meals or 300 mg PO 24 hrly w/ meals • GI effects (abdominal pain, diarrhea, nausea,
Up to 400 mg/day PO in divided doses constipation, elevated transaminase levels);
Micronized: 160-268 mg PO 24 hrly or in Other effects (back pain, asthenia, rhinitis)
divided doses Special Instructions
Nanotechnology formula: • Not recommended in patients w/ hepatic or
145 mg PO 24 hrly severe renal dysfunction, gallstones
Suprabioavailable formula: • Use w/ caution in mild-moderate renal
160 mg PO 24 hrly impairment
• Monitor serum transaminase levels regularly
Gemfibrozil Regular release: Adverse Reactions
600 mg PO 12 hrly • GI effects (abdominal pain, dyspepsia, N/V);
Max dose: CNS effects (headache, drowsiness,
1500 mg/day dizziness, vertigo); Other effects (rash,
gallstones, atrial fibrillation, eczema)
Extended-release:
• Myalgia, myopathy & rarely rhabdomyolysis:
900 mg PO 24 hrly in the evening occurs more often if combined w/ statins
• Not recommended in patients w/ severe
renal or hepatic dysfunction, gallstones
• Use w/ caution in mild-moderate renal
impairment
• Monitor serum transaminase levels regularly
FIBRATE/STATIN
Drug Available Strength Dosage Remarks
Fenofibrate/ Fenofibrate 160 mg/ Initially 1 tab PO Adverse Reactions

Atorvastatin Atorvastatin 10 mg, 24 hrly • CNS effects (headache, asthenia);
Fenofibrate 160 mg/ Max dose: GI effects (abdominal pain, nausea,
Atorvastatin 20 mg Fenofibrate 160 mg/ constipation, diarrhea)
Atorvastatin 40 mg • See Remarks section of each individual
DYSLIPIDEMIA
component for other adverse reactions

• Withhold use in patients w/ myopathy or a
risk factor predisposing to renal failure from
rhabdomyolysis
• Perform LFTs before & after 12 wk of
treatment, periodic blood counts during 1st
yr of treatment
• See Remarks section of each individual
component for other special instructions

B92
Dosage Guidelines
FIBRATE/STATIN (CONT’D)
Fenofibrate/ Fenofibrate 160 mg/ 1 cap PO 24 hrly Adverse Reactions

Pravastatin Pravastatin 40 mg • GI effects (abdominal distention & pain,
discomfort; constipation, diarrhea, dry mouth,
dyspepsia, eructation, flatulence, N/V, increased
transaminases)
• Should be taken w/ food & in the evening
• Avoid in patients w/ severe hepatic or renal
impairment, history of myopathy &/or
rhabdomyolysis, phototoxic reaction during
treatment w/ fibrates or Ketoprofen, gallbladder
disease, chronic or acute pancreatitis, CPK
elevation during previous statin treatment
• Use w/ caution in patients w/ history of liver
disease, pancreatitis, interstitial lung disease,
pulmonary embolism, galactose intolerance,
Lapp lactase deficiency or glucose-galactose
malabsorption
• Routine monitoring of CPK, transaminases,
liver & renal function every 3 mth during the
1st yr of treatment
Fenofibrate/ Fenofibrate 160 mg/ 1 tab PO 24 hrly Adverse Reactions
Rosuvastatin Rosuvastatin 10 mg, after dinner • GI effects (dyspepsia, flatulence, hepatitis,
Fenofibrate 160 mg/ cholecystitis); CNS effects (fatigue, numbness,
Rosuvastatin 20 mg insomnia, dizziness); Other effects
(photosensitivity, eczema, asthenia, flu
syndrome, rhinitis, myalgia)
• Use w/ caution in patients w/ risk of myopathy,
cholelithiasis, pancreatitis
Fenofibrate/ Fenofibrate 145 mg/ 1 tab PO 24 hrly Adverse Reactions
DYSLIPIDEMIA
Simvastatin Simvastatin 20 mg, • Metabolic effects (increased ALT, increased
Fenofibrate 145 mg/ blood creatinine); Other effects (upper resp
Simvastatin 40 mg tract infection, gastroenteritis, increased
platelet count)
• Contraindicated in patients w/ chronic or acute
pancreatitis w/ the exception of acute
pancreatitis due to severe hypertriglyceridemia
• Use w/ caution in patients w/ hepatic disorders,
pancreatitis, mild renal insufficiency

B93
Dosage Guidelines
NICOTINIC ACID DERIVATIVES

Drug Dosage Remarks
Acipimox 250 mg PO 8-12 hrly Adverse Reactions
Max dose: 1250 mg/day • GI effects (heartburn, epigastric pain, nausea, diarrhea);
CV effect (flushing); CNS effect (headache);
Hypersensitivity reactions (itching, rash); Musculoskeletal
effects (myalgia, arthralgia, myositis); Other effects (dry
eyes, malaise)
• Not recommended in patients w/ peptic ulcer & severe
renal impairment
• Use w/ caution in patients w/ renal impairment
Nicotinic acid Regular-release: Adverse Reactions
100-200 mg PO 8 hrly • CV effect (flushing); Metabolic effects (hyperglycemia,
Extended-release: hyperuricemia, gout); GI effects (cramps, diarrhea,
Administered 24 hrly at nausea); hepatotoxicity has occurred rarely
bedtime Special Instructions
Wk 1-4: 500 mg PO • To reduce flushing:
Wk 5-8: 1 g PO - Take w/ food
Adjust dose according to - Start w/ low dose & increase gradually
response & tolerability - Administer enteric-coated Aspirin 75-325 mg PO prior
every 4 wk by not >500 mg/ to dose
day
• Administer at bedtime
Maintenance: 1-2 g PO
24 hrly • Not recommended in chronic liver disease & in patients
w/ severe gout
Max dose: 2 g/day
• Use w/ caution in patients w/ DM & in patients w/
hyperuricemia
SELECTIVE CHOLESTEROL-ABSORPTION INHIBITOR

Drug Dosage Remarks
Ezetimibe 10 mg PO 24 hrly Adverse Reactions
• CNS effect (headache); GI effects (diarrhea, abdominal
pain); hypersensitivity reactions
DYSLIPIDEMIA
• When administered w/ a statin: Elevated transaminases,

muscle pain, tenderness or weakness
• Use w/ caution in patients w/ severe renal impairment
• Not recommended in patients w/ hepatic dysfunction

B94
Dosage Guidelines
SELECTIVE CHOLESTEROL-ABSORPTION INHIBITOR/STATIN

Ezetimibe/ Ezetimibe 10 mg/ Primary Adverse Reactions

Atorvastatin Atorvastatin 10 mg, hypercholesterolemia: • Common: Diarrhea, myalgia
Ezetimibe 10 mg/ 10 mg/10 mg or • See Remarks section of each individual
Atorvastatin 20 mg, 10 mg/20 mg PO 24 hrly component for other adverse reactions
Ezetimibe 10 mg/ Dose range: Special Instructions
Atorvastatin 40 mg, 10 mg/10 mg to • Can be administered at any time of the
Ezetimibe 10 mg/ 10 mg/80 mg PO 24 hrly day
Atorvastatin 80 mg If a large reduction in • Dosing should occur either ≥2 hr before
LDL-C (>55%) is or ≥4 hr after administration of a bile
required: May start at acid sequestrant
10 mg/40 mg PO 24 hrly • Perform LFTs before treatment &
Homozygous familial periodically thereafter
hypercholesterolemia: • Should not be used in patients w/ active
10 mg/10 mg to liver disease & in those w/ unexplained
10 mg/80 mg PO 24 hrly transaminase elevations >3x ULN
Ezetimibe/ Ezetimibe 10 mg/ Usual initial dose: • The 10/80 mg dose increases the chance
Simvastatin Simvastatin 10 mg, 10 mg/20 mg PO 24 hrly of developing muscle damage. The
Ezetimibe 10 mg/ in the evening 10/80 mg dose should only be used by
Simvastatin 20 mg, Dose range: patients who:
Ezetimibe 10 mg/ 10 mg/10 mg to - Have been taking this dose chronically
Simvastatin 40 mg, 10 mg/80 mg PO 24 hrly (≥12 mth) without having muscle
Ezetimibe 10 mg/ damage
If a large reduction in
Simvastatin 80 mg LDL-C (>55%) is - Do not need to take other medicines
required: May start at (eg Gemfibrozil, antifungals such as
10 mg/40 mg PO 24 hrly Ketoconazole & Itraconazole, HIV
in the evening protease inhibitors, Ciclosporin,
Nefazodone, certain antibiotics like
Homozygous familial Erythromycin, Clarithromycin &
hypercholesterolemia: Telithromycin) w/ this drug that would
10 mg/40 mg or increase the chance of getting muscle
10 mg/80 mg PO 24 hrly damage
in the evening • See Remarks section of each individual DYSLIPIDEMIA

B95
Dosage Guidelines
STATINS
Drug Dosage Remarks
Atorvastatin Initial dose: 10-20 mg PO 24 hrly any time of day Adverse Reactions
If a large reduction in LDL-C (>45%) is required: • Musculoskeletal effects
Start at 40 mg PO 24 hrly (myalgia, arthralgia, muscle
Dose range: 10-80 mg PO 24 hrly cramps); GI effects (nausea,
Primary hypercholesterolemia & mixed hyperlipidemia: abdominal pain, constipation);
10-20 mg PO 24 hrly Other effects (rash, headache,
Homozygous familial hypercholesterolemia: dizziness)
Usually 10-80 mg PO 24 hrly • Myopathy has occurred & is
usually associated w/ high dose,
Heterozygous familial hypercholesterolemia: when statin is combined w/
Initially 10 mg PO 24 hrly Nicotinic acid or fibrate, in
May be adjusted every 4 wk to 40 mg/day patients w/ renal or hepatic
Fluvastatin Initial dose: 20-40 mg PO 24 hrly in the evening impairment, serious infections,
May increase to: hypothyroidism & advanced age
Regular-release: 40 mg PO 12 hrly or 80 mg PO - Rarely has rhabdomyolysis
24 hrly in the evening occurred
Extended-release: 80 mg PO 24 hrly - Advise patient to consult
physician immediately if signs
Lovastatin Initial dose: 20 mg PO 24 hrly in the evening of muscle pain suggesting
May increase to 80 mg PO 24 hrly in the evening or myopathy occur (especially if
divided 12 hrly accompanied by fever &
Mild-moderate hypercholesterolemia: Start w/ 10 mg malaise)
PO 24 hrly in the evening Special Instructions
Dose range: 20-80 mg PO 24 hrly or in divided doses • Dose should be based upon the
Pitavastatin 1-2 mg PO 24 hrly individual’s lipoprotein profile
May increase to max of 4 mg/day • Increases in dose should be
done at ≥4-wk intervals based
Pravastatin Initial dose: 10-20 mg PO 24 hrly at bedtime upon patient’s response until
Dose range: 10-40 mg PO 24 hrly at bedtime desired lipoprotein level is
Rosuvastatin Initial dose: 5-10 mg PO 24 hrly; may increase to reached
20 mg PO 24 hrly after 4 wk • Dose may need to be adjusted
Primary hypercholesterolemia (including heterozygous based on concomitant
familial hypercholesterolemia), mixed dyslipidemia, medications
dysbetalipoproteinemia, isolated hypertriglyceridemia • Should not be used in patients
& for slowing atherosclerosis progression: Start w/ w/ active liver disease & in those
10 mg PO 24 hrly w/ unexplained transaminase
Homozygous familial hypercholesterolemia: Start w/ elevations
DYSLIPIDEMIA
20 mg PO 24 hrly • Liver function should be tested

Patient w/ severe hypercholesterolemia at high CV before or after 6-12 wk of
risk: Up to 40 mg PO therapy & w/ any dose increase
In cases where doses >20 mg is indicated, initiation of • Use w/ caution in patients w/
therapy should be under close specialist supervision renal impairment as the risk of
myopathy is increased
Simvastatin Initial dose: 5-20 mg PO 24 hrly in the evening • Simvastatin: Due to increased
Dose range: 5-40 mg PO 24 hrly in the evening risk of myopathy, including
Primary hypercholesterolemia, mixed dyslipidemia: rhabdomyolysis, use of 80 mg
10-20 mg PO 24 hrly at night, adjusted at 4 wk interval dose of Simvastatin should be
Dose range: 10-80 mg PO 24 hrly at night restricted to patients who have
Homozygous familial hypercholesterolemia: 40 mg been taking this dose
PO 24 hrly in the evening or 80 mg PO in 3 divided chronically (≥12 mth) without
doses of 20 mg, 20 mg & an evening dose of 40 mg evidence of muscle toxicity

B96
Dosage Guidelines
STATINS - OTHER COMBINATIONS

Atorvastatin/ Atorvastatin 10 mg/ Initially Adverse Reactions

Amlodipine Amlodipine 5 mg, Atorvastatin 10 mg/ • Atorvastatin: See specific adverse reactions
Atorvastatin 20 mg/ Amlodipine 5 mg on page 19
Amlodipine 5 mg, PO 24 hrly • Amlodipine: CNS effects (headache,
Atorvastatin 40 mg/ Max dose: dizziness, somnolence, fatigue); GI effects
Amlodipine 5 mg, Atorvastatin 80 mg/ (abdominal pain, nausea); Other effects
Atorvastatin 10 mg/ Amlodipine 10 mg (palpitations, flushing, edema)
Amlodipine 10 mg, daily Special Instructions
Atorvastatin 20 mg/ • Avoid in patients w/ active liver disease or
Amlodipine 10 mg, unexplained persistent elevations of serum
Atorvastatin 40 mg/ transaminases >3x upper limit of normal
Amlodipine 10 mg, (ULN)
Atorvastatin 80 mg/ • Use w/ caution in patients w/ heart failure,
Amlodipine 10 mg myopathy or risk factor predisposing to renal
failure from rhabdomyolysis
• Perform LFTs before treatment &
periodically thereafter
• Atorvastatin: See specific special instructions
on page 19
Atorvastatin/ Atorvastatin 10 mg/ 1 tab PO 24 hrly Adverse Reactions
Amlodipine/ Amlodipine 5 mg/ • GI effects (constipation, dyspepsia, N/V,
Perindopril Perindopril 5 mg, diarrhea); CNS effects (headache, dizziness,
Atorvastatin 20 mg/ paresthesia, asthenia); Musculoskeletal
Amlodipine 5 mg/ effects (myalgia, arthralgia, back pain, joint &
Perindopril 5 mg, ankle swelling); Metabolic effects
Atorvastatin 20 mg/ (hyperglycemia, abnormal LFT, increased
Amlodipine 5 mg/ blood creatine); CV effects (palpitations,
Perindopril 10 mg, hypotension); Other effects (nasopharyngitis,
Atorvastatin 20 mg/ hypersensitivity, epistaxis, flushing, edema,
Amlodipine 10 mg/ visual impairment, tinnitus, cough, dyspnea,
Perindopril 10 mg, rash, pruritus)
Atorvastatin 40 mg/ Special Instructions
Amlodipine 10 mg/ • Avoid in patients w/ hypersensitivity, liver
Perindopril 10 mg disease, severe hypotension, DYSLIPIDEMIA
hemodynamically unstable heart failure,
history of angioedema, significant bilateral
renal artery stenosis; on Sacubitril/Valsartan
• Use w/ caution in patients w/ collagen
vascular disease, on immunosuppressant
therapy, Allopurinol or Procainamide
decreased renal function; interstitial lung
disease on long-term therapy
• Monitor glycemic control & LFTs
periodically

B97
Dosage Guidelines
STATINS - OTHER COMBINATIONS (CONT’D)

Rosuvastatin/ Rosuvastatin 10 mg/ 1 cap PO 24 hrly Adverse Reactions

Aspirin Aspirin 80 mg, • Rosuvastatin: See specific adverse
Rosuvastatin 20 mg/ reactions on page 19
Aspirin 80 mg • Aspirin: Hypersensitivity
• Rosuvastatin: See specific special
instructions on page 19
• Avoid Aspirin in patients w/ active or
history of peptic ulceration,
hemophilia & other bleeding
disorders
• Use Aspirin w/ caution in patients w/
HTN; may induce GI hemorrhage
Simvastatin/ Simvastatin 20 mg/ Initially 20 mg Adverse Reactions
Ubidecarenone Ubidecarenone (Simvastatin) PO 24 hrly • Musculoskeletal effects (myopathy/
10 mg Adjust dose at intervals rhabdomyolysis, myalgia); GI effects
of not <4 wk (abnormal hepatic function,
Max dose: 80 mg constipation, abdominal pain, diarrhea);
(Simvastatin) PO 24 hrly Other effect (asymptomatic increase in
in the evening serum creatine kinase concentration)
• Use w/ caution in patients w/ severe
renal impairment, elevated
transaminase levels, history of or acute
liver disease, high alcohol consumption
• Avoid in patients w/ acute liver disease
or unexplained persistently raised
serum aminotransferase concentration
OTHER AGENTS
Drug Dosage Remarks
Benfluorex 150 mg PO 8 hrly Adverse Reactions
• GI effects (loose stools, N/V); CNS effect (drowsiness); Other
effect (fatigue)
DYSLIPIDEMIA
• Not recommended in patients w/ pancreatitis
Omega-3 fish 1-4 g/day PO in 2 Adverse Reactions
oils1 divided doses (of • GI effects (reflux, fish odor or taste, N/V, diarrhea, constipation);
(can be a a preparation rarely eczema & acne
combination of containing 46% • Moderate elevation of transaminases have been reported in
linolenic acid, EPA & 38% DHA) patients w/ hypertriglyceridemia
DHA, EPA) Special Instructions
• Due to moderate increase in bleeding time (w/ high dosage), patients
on anticoagulant therapy must be monitored & dosage of
anticoagulant adjusted as necessary
1Combination products are available & some may contain antioxidants (eg tocopherol).

B98
Dosage Guidelines
OTHER AGENTS (CONT’D)

Drug Dosage Remarks
Probucol 500 mg PO 12 hrly Adverse Reactions
• GI effects (GI upset, diarrhea, flatulence, pain, N/V);
Hypersensitivity reaction (angioedema); CV effect
(arrhythmias)
• Take w/ meals
• Use w/ caution in patients w/ recent myocardial damage,
history of arrhythmias, hypokalemia, prolonged QT interval or
CV-associated syncope
Standardized 600-1200 mg PO Adverse Reactions
red yeast 12 hrly • Mild GI upset (that can be alleviated if taken after meals)
rice Special Instructions
• Administer after meals
• Not recommended for use in individuals at risk for or having
history of liver disease, & those who are <20 yr of age
• Concomitant use w/ other anti-lipid agents is not
recommended
• Avoid if >2 drinks of alcohol per day have been consumed
• Use w/ caution in patients w/ serious infection, disease or
physical disorder; in patients who have undergone organ
transplant, recent major surgery
Tocopheryl 100-200 mg PO 8 hrly Adverse Reactions
nicotinate • GI effects (nausea, diarrhea, constipation, abdominal
(DL-alfa discomfort, anorexia); Other effects (flushing, edema, liver
tocopheryl dysfunction)
nicotinate)
Other Lipid Modifying Agents
Alirocumab 75 mg SC every 2 wk or Adverse Reactions
300 mg SC every 4 wk • Resp effects (nasopharyngitis, bronchitis, sinusitis, cough);
Max dose: 150 mg SC Musculoskeletal effects (myalgia, muscle spasms,
every 2 wk musculoskeletal pain); Other effects (inj site reactions, UTI, flu,
diarrhea, contusion)
Special Instructions DYSLIPIDEMIA
• Avoid in patients w/ serious hypersensitivity to Alirocumab
discontinue therapy
• Use w/ caution in patients w/ severe renal & hepatic impairment
Bempedoic Heterozygous familial Adverse Reactions
acid hypercholesterolemia: • Metabolic effects (hyperuricemia, gout); CV effects (increased
180 mg PO 24 hrly serum creatine kinase, atrial fibrillation); GI effects (abdominal
pain, abdominal distress); GU effect (benign prostatic
hyperplasia); Hematologic effects (thrombocytopenia,
leukopenia, anemia); Musculoskeletal effects (muscle pain, limb
pain, back pain, rupture of tendon); Other effects (increased liver
enzymes, increased serum creatinine, upper resp tract infection)
• Monitor for signs & symptoms of hyperuricemia & tendinopathy

B99
Dosage Guidelines

Drug Dosage Remarks
Other Lipid Modifying Agents (Cont’d)
Evolocumab Homozygous familial Adverse Reactions
hypercholesterolemia: • Homozygous familial hypercholesterolemia: Resp effects
420 mg SC once mthly (upper resp tract infection, nasopharyngitis); Other effects
Primary hypercholes- (influenza, gastroenteritis)
terolemia (heterozygous • Heterozygous familial hypercholesterolemia & primary
familial & nonfamilial), hyperlipidemia: Resp effects (upper resp tract infection,
mixed dyslipidemia or nasopharyngitis, cough); GI effects (gastroenteritis, diarrhea);
adults w/ established CNS effects (headache, dizziness); Other effects (influenza,
clinical ASCVD: back pain, inj site reactions, UTI, sinusitis, musculoskeletal
140 mg SC every 2 wk pain, hypertension, allergic reactions)
or 420 mg SC once Special Instructions
mthly • Avoid in patients w/ hypersensitivity
discontinue therapy
• Use w/ caution in patients w/ moderate-severe hepatic or
severe renal impairment
Icosapent 2 g PO 12 hrly Adverse Reactions
ethyl • CV effects (peripheral edema, atrial fibrillation, atrial flutter);
GI effects (constipation, abdominal distress); Musculoskeletal
effects (arthralgia, musculoskeletal pain, limb pain): Other
effects (hemorrhage, gout, oropharyngeal pain, increased
serum TG)
• Must be taken w/ meals
• Use w/ caution in patients w/ coagulopathy, known allergy or
sensitivity to fish or shellfish
Inclisiran Initially 284 mg SC inj Adverse Reactions
single dose, again at • Resp effects (dyspnea, bronchitis); Other effects (inj site
3 mth, followed by reaction, pain in extremity, arthralgia, UTI, diarrhea)
every 6 mth Special Instructions
• May be injected subcutaneously into the abdomen, upper arm,
or thigh; inj should not be given into areas of active skin
disease or injury
DYSLIPIDEMIA
• Hemodialysis should not be performed for at least 72 hr after

Inclisiran dosing
• Use w/ caution in patients w/ severe hepatic or renal
impairment

B100
Dosage Guidelines

Drug Dosage Remarks
Other Lipid Modifying Agents (Cont’d)
Lomitapide Initial dose: 5 mg PO Adverse Reactions
24 hrly • GI effects (N/V, dyspepsia, abdominal pain, hepatotoxicity,
May increase to 10 mg diarrhea); Other effects (chest pain, decreased wt, infections)
PO 24 hrly after ≥2 wk Special Instructions
of initiation, then • Take at least 2 hr after evening meal
additional 20 mg at
4-wk interval up to 60 mg • Contraindicated in patients taking CYP3A4 inhibitors & w/
based on safety & moderate-severe hepatic impairment or active liver disease
tolerability • May reduce absorption of fat-soluble vitamins & serum fatty
Max dose: 60 mg PO acids
24 hrly • Perform LFTs prior to initiation & w/ any dose increase
Mipomersen 200 mg SC once wkly Adverse Reactions
sodium • Inj site reactions (erythema, pain, tenderness, pruritus, local
swelling); Other effects (influenza-like illness, pyrexia, chills,
myalgia, arthralgia, malaise, fatigue, headache)
• Contraindicated in patients w/ moderate-severe hepatic
impairment, or active liver disease
• Perform LFTs at baseline & regularly during treatment
PERIPHERAL VASODILATORS & CEREBRAL ACTIVATORS

Drug Dosage Remarks
Peripheral Vasodilator
Xantinol Up to 3 g/day PO Adverse Reactions
nicotinate • Flushing, anxiety
(Xanthinol Special Instructions
nicotinate) • Avoid in patients w/ recent MI, decompensated cardiac
insufficiency, acute hemorrhage
• Use w/ caution in patients w/ active peptic ulcer, unstable
hypertension DYSLIPIDEMIA

B101
Heart Failure - Acute (1 of 27)
1
Patient presents w/ signs & symptoms of
possible acute heart failure
2
DIAGNOSIS ALTERNATIVE DIAGNOSIS
Is acute heart failure No
• Treat patient appropriately
confirmed?
Yes
MANAGEMENT
A Non-pharmacological therapy
• Supplemental O2
May consider non-invasive or mechanical ventilation as indicated
B Pharmacological therapy
• Diuretic (IV)
• Analgesic (eg Morphine) or sedative*
May consider mechanical circulatory support as indicated
Refer to Cardiovascular ICU if patient is in shock
3
CLASSIFY ACUTE HEART FAILURE
• Initiate specific therapy
SBP EVALUATION
Is patient’s SBP SBP
<85 mmHg >100 mmHg
or shock <85, 85-100, or
>100 mmHg?
SBP
85-100 mmHg
TREATMENT TREATMENT TREATMENT

PLAN FOR PLAN FOR PLAN FOR
PATIENTS W/ PATIENTS PATIENTS W/
SBP <85 mmHg W/ SBP 85- SBP >100 mmHg
See next page 100 mmHg See page 4
See page 3
*Benzodiazepines (Diazepam or Lorazepam) used cautiously may be the safest approach for sedation
B102
TREATMENT PLAN FOR

PATIENTS W/ SBP <85 mmHg
MANAGEMENT
• Supplemental O2
Inotropics
• Dobutamine
• Dopamine
• Epinephrine
• Norepinephrine
Other
• Correct over-diuresis or
hypovolemia, if required
Avoid vasodilators &
Morphine until BP is stabilized
SBP RESPONSE SBP

<85 mmHg & TO >100
cold extremities TREATMENT mmHg
MANAGEMENT MANAGEMENT
A Non-pharmacological therapy B Pharmacological therapy
• Non-invasive ventilation (NIV), • Nitrates (IV/sublingual)
endotracheal tube (ETT) or • Morphine
invasive ventilation if • Increase/continue diuretics as needed
SpO2* <90%
• Vasopressin antagonist
• Consider pulmonary artery
catheterization • ACE inhibitor/ARB/low-dose
beta-blocker
• If w/ signs of hypovolemia or
over diuresis, consider fluid
challenge w/ 100 mL IV infusion
& monitor response
C Interventional therapy
• Consider mechanical assist
devices, eg intra-aortic balloon RESPONSE
pump (IABP), left ventricular TREATMENT
See Heart Failure-
TO
assist device (LVAD), or Yes TREATMENT
percutaneous coronary Chronic disease
intervention (PCI) management Is patient
chart stable?
No
HEART FAILURE - ACUTE
*SpO2 is transcutaneous oxygen saturation.
B103
TREATMENT PLAN FOR

PATIENTS W/ SBP 85-100 mmHg
MANAGEMENT
• Supplemental O2
• Reduce diuretics
Inotropics
• Dobutamine
• Dopamine
• Epinephrine
• Norepinephrine
• Levosimendan
Other
• Correct over-diuresis or
hypovolemia, if required
Avoid vasodilators &
Morphine until BP is stabilized
SBP RESPONSE SBP

<85 mmHg & TO >100
cold extremities TREATMENT mmHg
MANAGEMENT MANAGEMENT
A Non-pharmacological therapy B Pharmacological therapy
• NIV, ETT, or invasive • Nitrates (IV/sublingual)
ventilation if SpO2 <90% • Morphine
• Consider pulmonary artery • Increase/continue diuretics as needed
catheterization • Vasopressin antagonist
• If w/ signs of hypovolemia or • ACE inhibitor/ARB/beta-blocker
over diuresis, consider fluid
challenge w/ 100 mL IV infusion
& monitor response
• Stop vasodilator
RESPONSE
• Consider mechanical assist TREATMENT TO
devices, eg IABP, LVAD, or PCI See Heart Failure- Yes TREATMENT
Chronic disease
management Is patient stable?
chart
No
B104
TREATMENT PLAN FOR

PATIENTS W/ SBP >100 mmHg
TREATMENT
• Nitrates (IV/sublingual)
• Morphine
• Diuretics
• Vasopressin antagonist
• ARB/ACE inhibitor/beta-blocker
TREATMENT
EVALUATION See Heart Failure-
Yes
Has patient Chronic disease
improved? management
chart
No
ADDITIONAL TREATMENT
• Address other underlying conditions
• Dobutamine
• Dopamine
• Phosphodiesterase inhibitor
• Nitroprusside
TREATMENT
EVALUATION See Heart Failure-
Yes
Has patient Chronic disease
improved? management
chart
No
MANAGEMENT
• NIV, ETT, or invasive ventilation if SpO2 <90%
• Consider pulmonary artery catheterization
• Stop vasodilator
• Stop beta-blocker if hypoperfused
• Consider inotropes
• Consider mechanical assist devices, eg IABP,
LVAD, or PCI
B105
1 ACUTE HEART FAILURE

Heart Failure
• A clinical syndrome caused by functional or structural impairment of ventricular filling or blood ejection
• Characterized by either left ventricular (LV) hypertrophy or dilation or both
• Leads to neurohormonal & circulatory abnormalities producing the following manifestations:
- Breathlessness/dyspnea at rest or on exertion
- Unexplained fatigue, tiredness
- Decreased exercise capacity or increased time to recover after exercise
- Orthopnea
- Bendopnea
- Paroxysmal nocturnal dyspnea (PND) or nocturnal cough
- Cough or wheezing
- Palpitations
- Anorexia, nausea, vomiting, abdominal pain, bloated feeling, early satiety, ascites
- Peripheral edema, ankle swelling
- Confusion, disorientation, cognitive decline
- Weakness, depression (especially in the elderly)
- Weight gain (>2 kg/week)
- Weight loss (in advanced heart failure)
- Syncope
• More specific signs typical of heart failure include elevated jugular venous pressure, hepatojugular reflux, apical
impulse that is laterally displaced, & presence of S3 (gallop rhythm)
Acute Heart Failure
• Rapid or gradual onset of or change in the signs &/or symptoms of heart failure
• Arises as a result of acute cardiac function deterioration in patients previously diagnosed w/ heart failure or
may also be the first presentation of heart failure
• Cardiac dysfunction may be related to ischemia, arrhythmia, valvular abnormalities, pericardial disease,
increased filling pressure or elevated systemic resistance
• Characterized by pulmonary congestion, decreased cardiac output, & tissue hypoperfusion
- Most acute heart failure patients present w/ normal or high blood pressure (BP) & signs &/or symptoms of
congestion instead of low cardiac output
• Life-threatening condition that needs immediate medical attention
• May be transient & reversible w/ resolution of the acute syndrome or may induce permanent damage leading
to chronic heart failure
2 DIAGNOSIS
The diagnosis of acute heart failure is based on clinical findings supported by appropriate diagnostic exam
performed urgently after first patient contact; identifies patients in cardiogenic shock & respiratory failure
Clinical Assessment
• History
• Physical Exam
- Vital signs (eg low or high BP, bradycardia, tachycardia w/ pulsus alternans, irregular pulse, tachypnea,
increased work of breathing, apnea or hypopnea w/ respiratory rate <8 breaths/minute despite dyspnea,
intolerance of supine position) & patient's body mass index (BMI)
- Assess hemodynamic status, heart rhythm & level of dyspnea to determine degree of cardiopulmonary
instability
- Check for murmurs, laterally displaced or prominent apex beat, S3 gallop & accentuated pulmonic component
of the 2nd heart sound
- Hypoperfusion: Low output state usually caused by pump failure (eg cold sweated extremities, oliguria,
narrow pulse pressure, altered mental status, dizziness, capillary refill time >2 seconds)
- Often accompanied by but is not synonymous w/ hypotension
- Congestion: Left-sided [bilateral pulmonary rales, bilateral peripheral edema (eg ankle, sacral, scrotal)] or
right-sided (elevated jugular venous pressure, bilateral peripheral edema, hepatomegaly, ascites, hepatojugular
reflux) volume overload
B106
Clinical Assessment (Cont'd)
• Based on the physical exam, acute heart failure can be classified based on the presence or absence of congestion
&/or hypoperfusion
- Warm-dry: Both congestion & hypoperfusion are absent
- Warm-wet: Congestion present but without hypoperfusion
- Cold-dry: Hypoperfusion present but without congestion
- Cold-wet: Both congestion & hypoperfusion are present
Laboratory/Diagnostic Tests
Tests to Consider in All Patients w/ Suspected Heart Failure
• Complete blood count (CBC), serum electrolytes, blood urea nitrogen (BUN), creatinine/estimated glomerular
filtration rate (GFR), glucose, troponin, uric acid, calcium, magnesium, albumin, lipid profile, liver enzymes,
bilirubin, serum ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), cardiac enzymes,
thyroid function tests, international normalized ratio (INR), C-reactive protein (CRP), & urinalysis
- To detect reversible/treatable causes of heart failure & presence of other comorbidities
- May also consider a pulse oximetry & arterial blood gas analysis in case of respiratory distress, lactate in
case of hypoperfusion, & D-dimer & procalcitonin in case of suspected pulmonary embolism & pneumonia
respectively
• Electrocardiogram (ECG)
- To assess cardiac rate & rhythm, conduction, electrical dyssynchrony, chamber enlargement, QTc interval
& detect presence of myocardial infarction (MI) or ischemia; has a high negative predictive value
- Performed immediately in patients w/ suspected cardiogenic shock
• Chest radiography
- To rule out other non-cardiac causes of dyspnea & to evaluate heart size, presence of congestion, pulmonary
or other diseases & proper placement of implanted cardiac devices
- Specific findings for acute heart failure include cardiomegaly, pulmonary venous congestion, pleural effusion
& interstitial or alveolar edema
• Echocardiography
- To determine cardiac structure & function
- Method of choice in patients w/ suspected heart failure because of its accuracy, availability, safety & cost
- Consider doing within 48 hours of admission for early management guidance if patient is hemodynamically
unstable & after stabilization particularly w/ de novo disease; performed immediately in patients w/
suspected cardiogenic shock
- May be performed if natriuretic peptide levels are elevated to rule out cardiac abnormalities
- Specific findings for acute heart failure include global LV systolic dysfunction, LV diastolic dysfunction &
inferior vena cava congestion
• Plasma natriuretic peptide [eg B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), mid-regional
pro atrial natriuretic peptide (MR-proANP)]
- Acute heart failure is associated w/ increased plasma levels of natriuretic peptides:
- BNP ≥100 pg/mL, NT-proBNP ≥300 pg/mL, MR-proANP ≥120 pg/mL
- Recommended upon presentation in patients w/ dyspnea who are suspected to have heart failure, especially
when the diagnosis is uncertain, also to exclude other causes of dyspnea
- May be utilized to establish prognosis of heart failure on admission & predischarge
- May also be used to screen individuals at risk of developing heart failure
• Measure cardiac biomarkers [eg cardiac troponin T (cTNT), highly sensitive troponin T (HsTNT)] in patients
who present w/ acute decompensated heart failure
• Coronary angiography
- To evaluate the coronary anatomy [ie establishes the presence & extent of coronary artery disease (CAD)]
- Recommended in patients w/ angina pectoris & patients w/ cardiogenic shock who are suitable for coronary
revascularization
- A multidetector computed tomography (MDCT) study may be used as an alternative to invasive coronary
angiography in select patients to rule out significant CAD
• Cardiac catheterization
- To evaluate patients for heart transplantation or mechanical circulatory support
- To assess right & left heart function & pulmonary arterial resistance
• Cardiac magnetic resonance (CMR) imaging

- To evaluate cardiac structure & function
- To characterize cardiac tissue, especially in patients w/ inadequate echocardiographic images or inconclusive
echocardiographic findings in poorly understood conditions such as innocuous myocarditis
• Myocardial perfusion/ischemia imaging [eg echocardiography, CMR, single photon emission computed
tomography (SPECT) or positron emission tomography (PET)]
- To assess the presence of reversible myocardial ischemia & viable myocardium
- Should be considered in patients who are suspected to have CAD & who are suitable for coronary
revascularization
B107
Laboratory/Diagnostic Tests (Cont'd)
Tests to Consider in All Patients w/ Suspected Heart Failure (Cont'd)
• Exercise testing
- To detect the presence of reversible ischemia
- Allows objective evaluation of exertional symptoms & exercise capacity to aid in prescribing an exercise
training program
- Aids in the evaluation of patients for heart transplantation & mechanical circulatory support & to obtain
prognostic information
- Caution must be observed in patients w/ acute heart failure & exercise testing is done when patients are
more stable
• Endomyocardial biopsy
- May be used in patients w/ rapidly progressive clinical heart failure or ventricular dysfunction despite
appropriate medical treatment & those who are suspected of having myocarditis or infiltrative diseases
MANAGEMENT
Management should include rapid identification, stabilization of clinical & hemodynamic status together
w/ determination & treatment of the primary pathology, precipitating factors & aggravating secondary
causes
• Treatment strategy for acute heart failure is similar in patients w/ & without COVID-19 infection
Goals of Treatment in Acute Heart Failure
• Treat symptoms, stabilize the patient & improve hemodynamics, congestion & organ perfusion
- Titrate supplemental oxygen to achieve SpO2 >95% & maintain systolic blood pressure (SBP) >90 mmHg &
peripheral perfusion
- Fluid challenge w/ saline or Ringer’s lactate is recommended in patients w/ cardiogenic shock if without
overt signs of fluid overload
• Identify etiology & comorbid illnesses & initiate specific therapy
• Limit organ damage (cardiac, renal, hepatic, gut) & prevent thromboembolism
• Adjust therapy to control symptoms, manage congestion & hypoperfusion, & optimize BP
• Initiate & assess the need to increase disease-modifying pharmacological therapy
• Minimize side effects
• Consider device therapy in appropriate patients
• Create a plan of care that includes medical & device therapy & follow-up
• Educate & initiate lifestyle modification & improve symptoms, quality of life & survival
• Prevent early readmission
Refer Patient to Cardiovascular Intensive Care Unit (ICU)
• W/ acute heart failure & associated shock or acute coronary syndrome (ACS)
- Patients at high risk for ACS may also be referred to the cardiac catheterization lab
• Vital signs include SBP <90 mmHg, heart rate <40 beats/minute (bpm), respiratory rate >25 breaths/minute,
SpO2 <90%, use of accessory respiratory muscles
• Arrhythmias
• There is a need for intubation or is already intubated
• Signs of hypoperfusion are present, eg altered mental status, cold extremities, metabolic acidosis, oliguria,
lactate >2 mmol/L, SvO2 <65%
• Poor response to non-invasive ventilation or to high fraction of inspired oxygen (FiO2)
• Requirement for ≥2 vasoactive drugs to maintain BP, for invasive cardiac output monitoring, or for mechanical
circulatory support
Management of Patients Based on Clinical Profile in the Initial Phase
• Warm-dry: Compensated patients w/ adequate peripheral perfusion will have adjustment of oral therapy
• Warm-wet
- Predominant congestive symptoms: Give diuretic, vasodilator; consider ultrafiltration if resistant to diuretic
therapy
- Predominant hypertension: Give vasodilator, diuretic
• Cold-dry: May consider fluid challenge or an inotropic agent if patient is still hypoperfused
• Cold-wet
- If SBP <90 mmHg: Give an inotropic agent, diuretic when perfusion is corrected; in refractory cases (eg
hypoperfusion & congestion), may consider giving a vasopressor
- If unresponsive to medical therapy (eg persistent hypoperfusion or organ damage), may consider mechanical
circulatory support &/or renal replacement therapy
- If SBP >90 mmHg: Give vasodilators, diuretics; in refractory cases, may consider giving an inotropic agent
B108
3 CLASSIFICATION OF ACUTE HEART FAILURE

Clinical Conditions of Acute Heart Failure
Patients w/ acute heart failure may present in one of the following clinical categories
Worsening or Decompensated Heart Failure
• Usually w/ a history of progressive worsening of chronic heart failure on treatment & evidence of systemic &
pulmonary congestion & increased intraventricular pressure
• Hypotension on admission is associated w/ a poor prognosis
Pulmonary Edema
• Patients present w/ severe respiratory distress, tachypnea, orthopnea & w/ rales over the lung fields
• Arterial O2 saturation is usually <90% on room air prior to oxygen therapy
• Confirmed by chest radiography
Isolated Right Heart Failure
• Low output syndrome in the absence of pulmonary congestion w/ elevated jugular venous pressure, w/ or
without hepatomegaly & low LV filling pressures
• SBP & cardiac output are low & right ventricular end-diastolic pressure is increased
Cardiogenic Shock
• Tissue hypoperfusion induced by heart failure after adequate correction of preload & major arrhythmia
• Characterized by hypotension (SBP <90 mmHg, mean arterial pressure <60 mmHg or a decrease of >30 mmHg
from baseline SBP) & absent or low urine output of <0.5 mL/kg/hr
• Rhythm disturbance is common
• Pulmonary congestion & organ hypoperfusion develop rapidly
• There is continuum from low cardiac output syndrome to cardiogenic shock
Hypertensive Heart Failure
• Signs & symptoms of heart failure accompanied by high BP & preserved LV function (heart failure w/ preserved
ejection fraction)
• Evidence of increased sympathetic tone w/ tachycardia & vasoconstriction
• May be mildly hypervolemic or euvolemic w/ signs of pulmonary congestion without signs of systemic
congestion
• Rapid response to appropriate treatment & low hospital mortality
Acute Coronary Syndrome & Heart Failure
• Some patients w/ ACS present w/ symptoms & signs of heart failure
• Episodes of heart failure are associated w/ or precipitated by arrhythmia
• Patients are managed according to the ACS guidelines
Acute Mechanical Causes
• Conditions include acute incompetence of the native or prosthetic valve due to endocarditis, aortic dissection
or thrombosis, cardiac intervention, chest trauma, or ACS complicated by rupture of the myocardium (acute
mitral regurgitation, free wall rupture, ventricular septal defect)
Causes of Acute Heart Failure
• Tachyarrhythmia (eg atrial fibrillation, ventricular tachycardia), severe bradycardia or conduction abnormalities
• ACS or its complications (eg rupture of interventricular septum, mitral valve chordal rupture, right ventricular
infarction, acute mitral regurgitation)
• Pericardial tamponade
• Pulmonary embolism
• Hypertensive crisis or uncontrolled hypertension
• Aortic dissection
• Surgery & perioperative problems
• Peripartum or stress-related cardiomyopathy
• Infection (eg infective endocarditis, pneumonia, sepsis)
• Chronic obstructive pulmonary disease (COPD) exacerbation
• Cerebrovascular insult
• Noncompliance to diet or drug therapy

• Medications [nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, cardiotoxic chemotherapeutics,
negative inotropic agents]
• High output states (eg severe anemia, thyrotoxicosis)
• Fluid overload (eg volume overload causing pulmonary edema in acute kidney injury, iatrogenic causes)
• Toxic substances (recreational drugs, alcohol)
B109
A NON-PHARMACOLOGICAL THERAPY
• Elevate back rest to position of comfort & limit total fluid intake to <1-1.5 L/day
Ventilation
Oxygen
• Should be given to treat hypoxemic patients (SpO2 <90% or PaO2 <60 mmHg) in order to maintain O2 saturation
at ≥95% (≥90% in patients w/ COPD)
• Should not be used routinely in nonhypoxemic patients because it causes vasoconstriction & decreases cardiac
output
High-Flow Nasal Cannula
• Studies show it to be non-inferior to non-invasive positive pressure ventilation (NIPPV) & more effective than
conventional oxygen therapy
Non-invasive Ventilation (NIV)
• Continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP) & NIPPV relieve dyspnea
& improve oxygen saturation in patients w/ acute pulmonary edema
• Adjunctive therapy to relieve symptoms in patients w/ pulmonary edema & severe respiratory distress who
are not responsive to pharmacological therapy
• Considered in patients w/ conditions complicated by respiratory failure, decreased consciousness or physical
exhaustion
• Initiated as soon as possible to reduce respiratory distress & decrease the rate of endotracheal intubation
• Use w/ caution in hypotensive patients & those w/ reduced preload reserve; contraindicated in patients w/
vomiting, possible pneumothorax & altered sensorium
Endotracheal Intubation & Invasive Ventilation
• Indicated in patients w/ progressive respiratory failure, which may lead to hypoxemia, hypercapnia & acidosis,
that cannot be managed through non-invasive measures
• Also considered in patients w/ physical exhaustion, decreased consciousness, inability to maintain the airway
& persistent hemodynamic instability
Monitoring
Non-invasive Monitoring
• Monitoring the temperature, respiratory rate & effort, heart rate & rhythm (ECG), BP, oxygenation, cognitive
status, intake & output & peripheral perfusion is mandatory
• Evaluate patient’s signs & symptoms daily for correction of fluid overload
• Pulse oximeter should be used continuously in any unstable patient who is on oxygen therapy
• Transcutaneous arterial oxygen saturation monitoring is recommended for patients on oxygen therapy &
ventilatory support
- Venous blood gas may be used as an alternative to arterial blood gas if risk of vascular injury is present
• Acid-base balance should also be checked on admission in cases of acute pulmonary edema or prior history
of COPD
• While admitted in the hospital, patient monitoring should also include daily measurement of weight, renal
function & electrolytes
Invasive Monitoring
Intra-arterial Line
• Insertion of an intra-arterial line should only considered in patients w/ low SBP & persistent heart failure
despite treatment, eg cardiogenic shock
Central Venous Line
• Multiple lumen catheters are useful for fluids & drugs administration & monitoring of central venous pressure
& venous oxygen saturation which provides an estimate of the body oxygen consumption/delivery ratio
Pulmonary Artery Catheterization
• Measures the cardiac output & superior vena, right atrium, right ventricle & pulmonary artery pressures
• Can be used to identify the etiology of hypotension or end-organ dysfunction in patients w/ cardiogenic shock
unresponsive to empiric initial shock management & to distinguish between a cardiogenic & non-cardiogenic
mechanism in patients w/ concurrent cardiac & pulmonary disease
• Should not be routinely performed in hemodynamically stable patients w/ acute heart failure
- Should only be considered in patients who are refractory to pharmacological therapy, persistently hypotensive,
have uncertain LV filling pressure or being considered for surgery
B110
B PHARMACOLOGICAL THERAPY
Diuretics
• Eg loop diuretics, potassium-sparing diuretics, thiazide diuretics
• Cornerstone of treatment for patients w/ acute heart failure
• Restore & maintain normal volume status in patients w/ fluid overload
- Dose of intravenous (IV) diuretic should be based on the type of acute heart failure in patients w/ volume
overload & titrated to reduce congestive symptoms
- Recommended to be given either as intermittent boluses or as continuous infusion
• Provides rapid symptomatic relief in patients w/ pulmonary edema
• Low-dose combinations of loop diuretics w/ thiazides or aldosterone antagonists are often more effective &
w/ fewer side effects than high-dose monotherapy
- Can be used to treat resistant edema or patients w/ insufficient treatment response & achieve & maintain
euvolemia w/ the lowest effective dose
- Adjust dose after restoring the patient’s dry weight to avoid the risk of dehydration
• On admission, consider giving a higher dose of diuretic than that which patient is currently taking unless there
are contraindications
- Initial IV dose of patients receiving chronic diuretic therapy should be at least equivalent to the oral dose
- Monitor closely symptoms, weight, renal function & electrolytes & urine output during diuresis
- A satisfactory diuresis is a urinary sodium of ≥50-70 mEq/L after 2 hours &/or urine output of ≥100-150
mL/hr after 6 hours
• Continue oral loop diuretics at the lowest possible dose once congestion is relieved
• Patients w/ hypotension, hyponatremia & acidosis are unlikely to respond to diuretic treatment
Loop Diuretics
• Eg Bumetanide, Furosemide, Torasemide
• Considered as the diuretic class of choice for the treatment of heart failure
• Dose given is the smallest amount that can give adequate clinical response & adjusted based on prior renal
function & prior dose of diuretic agents
- Initial IV dose of Furosemide drip should be at least equivalent to the preexisting oral dose
• Higher doses of IV loop diuretics or addition of another diuretic is reasonable w/ inadequate diuresis
Potassium-Sparing Diuretics
• Eg Amiloride, Triamterene
• Have no direct diuretic activity
• Formulated in combination w/ thiazides for the treatment of hypertension
• Concomitant administration of these agents can be helpful in patients w/ excessive potassium losses secondary
to loop diuretics
Thiazide Diuretics
• Eg Bendroflumethiazide, Hydrochlorothiazide, Indapamide, Metolazone
• May be effective as monotherapy in patients w/ heart failure w/ mild volume overload & preserved renal
function
• More effective as antihypertensive agents than loop diuretics
Vasopressin Antagonists
• Eg Conivaptan, Tolvaptan
• Promote aquaresis by blocking the action of arginine vasopressin at the V2 receptor in the renal tubules
• Used in treating patients w/ volume overload & resistant hyponatremia
- Administered to patients w/ fluid retention unresponsive to treatment w/ other diuretics including loop
diuretics (excluding those w/ hypernatremia)
Opiates
• Eg Morphine
• Induce mild venodilatation & mild arterial dilatation leading to reduction in preload, heart rate & sympathetic
drive
• May be used in some patients w/ acute pulmonary edema to decrease anxiety & relieve distress associated w/
dyspnea
• Should not be routinely offered to patients w/ acute heart failure except for those w/ intractable/severe pain
or anxiety
Vasodilators
• Eg Nesiritide, Nitroglycerin, Nitroprusside
• Reduces venous & arterial tone resulting in optimization of preload & reduction in afterload respectively
• Mostly used in patients w/ hypertension
- IV therapy may be given as initial treatment when patient's SBP is >110 mmHg to reduce congestion &
improve symptoms; sublingual nitrates may be considered alternatives
• May be considered as an adjunct to diuretics for rapid improvement of congestive symptoms in patients w/
acute decompensated heart failure without systemic hypotension or significant obstructive valvular heart
disease (eg mitral or aortic stenosis)
• Slow titration w/ frequent BP monitoring is recommended
- Reduce dose or discontinue use if symptomatic hypotension or worsening renal function develops
- Reintroduction in incremental doses can be done once symptomatic hypotension resolves
B111
B PHARMACOLOGICAL THERAPY (CONT’D)

Vasodilators (Cont’d)
Nesiritide
• Recombinant B-type natriuretic peptide developed for the treatment of acute heart failure
• Causes dose-dependent decrease in filling pressure, systemic & pulmonary vascular resistance & an increase
in cardiac output
• Recently shown to decrease dyspnea by a small but significant amount when added to conventional therapy
such as diuretics
Nitroglycerin
• Decreases pulmonary congestion by acutely decreasing LV filling pressure
• May enhance coronary blood flow making it more effective in patients w/ acute decompensated heart failure
secondary to acute ischemia or MI, hypertension or significant mitral regurgitation
Nitroprusside
• Potent vasodilator w/ balanced effects on venous & arteriolar tone, ie decrease in systemic vascular resistance
• Causes immediate decrease in pulmonary capillary wedge pressure & increase in cardiac output
• Used in patients w/ severe congestion & hypertension or LV dysfunction complicated by mitral valve
regurgitation
• May be used as an alternative in patients unresponsive to nitrates
• Used w/ caution in patients w/ renal dysfunction because of possible thiocyanate toxicity
Inotropic Agents
• Eg Dobutamine, Dopamine, Levosimendan, phosphodiesterase inhibitors, Norepinephrine, Epinephrine
• Considered in patients w/ advanced heart failure or low output syndrome or unresponsive to or intolerant of
IV vasodilators
• May be considered in patients w/ hypotension (SBP <90 mmHg) & hypoperfusion (ie cardiogenic shock), who
are unresponsive to standard treatment including fluid challenge, for increasing BP & cardiac output, improve-
ment of peripheral perfusion & maintenance of end-organ function
• If hypotension w/ subsequent hypoperfusion is deemed to be from beta-blocker therapy, consider giving
Levosimendan or a phosphodiesterase inhibitor (eg Milrinone)
• Continuous BP & cardiac rhythm monitoring are recommended because inotropes & vasopressors may induce
myocardial ischemia, arrhythmia & hypotension
Dobutamine
• Positive inotropic agent which stimulates beta1 & beta2 receptors
• At low doses, Dobutamine induces mild arterial vasodilatation which augments stroke volume by decreasing
afterload while at higher doses, it causes vasoconstriction
• Increases cardiac output in patients w/ cardiogenic shock
Dopamine
• Endogenous catecholamine which involves dopaminergic, beta-adrenergic, & alpha-adrenergic receptors
• At low doses (<3 mcg/kg/min), causes selective vasodilation in the renal, splanchnic, coronary & cerebral
vascular beds causing increase renal blood flow, w/ an increased response to diuretics
• At intermediate doses (3-5 mcg/kg/min), it has inotropic effects which cause an increase in myocardial
contractility & cardiac output
• At higher doses (>5 mcg/kg/min), it has vasoconstrictor activity causing an increase in peripheral vascular
resistance
Levosimendan
• Calcium sensitizer which improves cardiac contractility by binding to troponin-C in cardiomyocytes
• Increases cardiac output & stroke volume, decreases pulmonary wedge pressure, systemic vascular resistance
& pulmonary vascular resistance, & slightly increases heart rate & decreases BP
• Alternative for patients on beta-blockers because its inotropic effect is independent of beta-adrenergic
stimulation
Phosphodiesterase Inhibitors
• Eg Amrinone, Enoximone, Milrinone
• Have significant inotropic, lusitropic & peripheral vasodilating effects

• Indicated in patients w/ peripheral hypoperfusion w/ or without congestion who are resistant to diuretics &
vasodilators & preserved systemic BP
• May be preferred than Dobutamine in patients on concomitant beta-blocker &/or w/ inadequate response to
dobutamine
B112

Inotropic Agents (Cont'd)
Vasopressors
• Eg Epinephrine, Norepinephrine
• Agents w/ prominent peripheral arterial vasoconstrictor activity which increase BP & redistribute cardiac
output from the extremities to the vital organs
• Cardiac-stimulant effect is more pronounced at low doses & vasoconstrictor effect at high doses
• Reserved for use in emergencies to maintain perfusion in life-threatening persistent hypotension in spite of
adequate filling status
• Should be used w/ caution & only transiently because it may increase LV afterload which may further decrease
end-organ perfusion
• If vasopressors are needed in patients w/ cardiogenic shock, Norepinephrine is recommended over Dopamine
Prophylaxis for Thromboembolism
• Eg low-molecular-weight Heparin, unfractionated Heparin, Fondaparinux, direct oral anticoagulant (DOAC)
• Reduces the risk of developing deep venous thrombosis & pulmonary embolism
• Recommended in patients not anticoagulated & without contraindication to anticoagulation therapy
Drugs After Stabilization
• Oral disease-modifying therapy for heart failure should be continued during acute heart failure episodes except
in patients who are hemodynamically unstable or w/ biochemical adverse reactions
• Evidence-based oral medical treatment is recommended to be given prior to discharge
• Recommended for prevention of heart failure in patients at high risk of this syndrome (eg those w/ peripheral
vascular disease (PVD), CAD, stroke, diabetes mellitus (DM), patients w/ another major risk factor or DM
patients who smoke or have microalbuminuria)
• Recommended in patients w/ left ventricular ejection fraction (LVEF) ≤40%, after stabilization of acute heart
failure, to decrease the risk of premature death, recurrent MI & hospitalization for heart failure
Angiotensin Receptor Blockers (ARB)/Angiotensin II Antagonists
• Alternative agents in patients w/ decreased LVEF, symptomatic atherosclerotic cardiovascular disease or DM
& another risk factor, who cannot tolerate the side effects of ACE inhibitors
• Also reduce the risk of premature death, recurrent MI & hospitalization for heart failure
Beta-Blockers
• Recommended in patients w/ recent decompensation of heart failure after optimization of volume status &
discontinuation of IV diuretics, vasoactive agents & inotropes
• Should be given in a "start low, go slow" approach until maximum tolerable doses & patient's clinical status,
BP & heart rate are reassessed after each dose titration
• Used in patients w/ symptomatic heart failure, LVEF <40% or LV systolic dysfunction after MI & patients w/
atrial fibrillation for acute control of ventricular rate
- Use cautiously if patient is hypotensive
- Consider Digoxin in patients w/ atrial fibrillation w/ rapid ventricular rate despite beta-blocker therapy
• Decrease cardiac ischemia, reinfarction, & myocardial remodeling after acute MI
• Should be & can be safely continued in patients w/ acute heart failure except in cardiogenic shock
- Discontinue beta-blockers in patients taking these medications if they have a heart rate of <50 bpm, 2nd- or
3rd-degree AV block or shock
Mineralocorticoid Receptor Antagonists (MRA)/Aldosterone Antagonists
• May be given after stabilization since it has minimal effect on BP
• Recommended in patients following an acute MI, w/ clinical heart failure manifestations or history of DM &
LVEF <40%, while receiving standard therapy
• Offered as an alternative if ACE inhibitor or ARB is not tolerated
Cardiac Glycosides
• Positive inotropic effect of cardiac glycosides does not change in heart failure
• Produce a small increase in cardiac output & reduction of filling pressures
• Indicated in patients w/ acute heart failure secondary to atrial fibrillation w/ insufficient rate control
• May be used in patients w/ sinus rhythm w/ symptomatic heart failure & LVEF ≤40%
B113
C INTERVENTIONAL THERAPY
Mechanical Assist Devices
• Temporary mechanical circulatory assistance may be indicated in patients w/ acute heart failure who have
potential for myocardial recovery but unresponsive to conventional treatment
• Mechanical circulatory support used in the short term may be considered in patients w/ refractory cardiogenic
shock depending on patient’s age, presence of comorbidities & neurological function
- Can also be used as a bridge to heart transplantation that may lead to significant recovery of the heart function
(bridge to recovery, bridge to decision or bridge to bridge)
Intra-aortic Balloon Pump (IABP) Counterpulsation
• Standard component of therapy in cardiogenic shock or severe acute left heart failure in patients who:
- Do not respond rapidly to fluid administration, vasodilatation & inotropic support
- Are complicated by significant mitral regurgitation or rupture of the interventricular septum
- Have severe myocardial ischemia in preparation for coronary angiography & revascularization
• Should only be used in patients who may recover spontaneously or whose underlying condition may be corrected
by coronary revascularization, valve replacement or heart transplant
• Contraindicated in patients w/ aortic dissection, significant aortic insufficiency, severe PVD, uncorrectable
causes of heart failure or multi-organ failure
Ventricular Assist Devices
• Mechanical pumps that partially replace the mechanical work of the ventricle
• Decrease myocardial work & pump blood into the arterial system thus increasing peripheral & end-organ flow
• Considered in patients w/ >2 months of severe symptoms despite optimal medical & device treatment who
have >1 of the following conditions (either as a destination therapy or a bridge to cardiac transplantation):
- LVEF <25% & peak maximum oxygen consumption <12 mL/kg/min
- ≥3 heart failure hospitalizations in the last 12 months w/ no known precipitating cause
- Dependence on IV inotropes
- Progressive end-organ dysfunction from reduced perfusion
- Without deteriorating right ventricular function
• Complications include thromboembolism, bleeding, infection & device malfunction
Ultrafiltration
• One of the most common approaches of renal replacement therapies
• Used to remove fluid in patients w/ heart failure who are not responsive to diuretics
Coronary Revascularization
• Can be considered in patients w/ heart failure & suitable coronary anatomy for relief of refractory angina or
ACS
• Following revascularization, patients may be referred for cardiac rehabilitation
- Meta-analyses demonstrate that cardiac rehabilitation improves functional capacity, exercise duration &
health-related quality of life & decreases hospitalizations & mortality in patients w/ heart failure
Valvular Surgery
• May be indicated in patients w/ valvular heart disease as the etiology of heart failure or as an important
aggravating factor for heart failure
• Surgical or percutaneous intervention may be performed after stabilization & optimal medical management
of heart failure & comorbid conditions
• Emergency surgery should be avoided if possible
B114
Dosage Guidelines
ACE INHIBITORS
Drug Dosage Remarks
Benazepril Initial dose: 2.5 mg PO 24 hrly Adverse Reactions

Adjust dose gradually according to • CV effects (hypotension, palpitations); CNS effects
response (fatigue, headache, dizziness); GI effect (taste
Max dose: 20 mg/day disturbances); Resp effects (persistent dry cough,
upper resp tract symptoms); Dermatologic effects
Captopril Initial dose: (skin rashes, erythema multiforme, toxic epidermal
6.25-12.5 mg PO 8 hrly necrolysis, pruritus, angioedema, photosensitivity
Adjust dose gradually according to reaction); Renal effect (renal impairment); Other
response effects (electrolyte disturbances, eg hyperkalemia,
Maintenance dose: 25 mg PO hyponatremia; blood disorders)
8-12 hrly or 50 mg PO 8 hrly Special Instructions
Max dose: 150 mg/day • Patients w/ heart failure & those who may be salt or
Cilazapril Initial dose: 0.5 mg PO 24 hrly water depleted (taking diuretic or on dialysis) may
experience hypotension during initial stages of ACE
Maintenance dose: 1-2.5 mg PO
inhibitor therapy
24 hrly
- Start treatment only under close medical
Max dose: 5 mg PO 24 hrly
supervision; in these patients use a low dose & have
Enalapril Initial dose: 2.5 mg PO 24 hrly the patient in a supine position
Maintenance dose: 20 mg PO • Start w/ low dose & if lower doses have been
24 hrly or divided 12 hrly tolerated, gradually increase dose every 2 wk until
Max dose: 40 mg/day maximum tolerated dose is achieved
Fosinopril Initial dose: 10 mg PO 24 hrly • Avoid in patients w/ aortic stenosis, mitral stenosis,
outflow tract obstruction, renovascular disease (eg
Adjust dose gradually according to renal artery stenosis, severe renal insufficiency) &
response hereditary or idiopathic angioedema
Max dose: 40 mg/day • Should not be given to patients if they have
Imidapril Initial dose: 2.5 mg PO 24 hrly experienced life-threatening adverse reactions
Max dose: 10 mg/day (angioedema or renal failure) w/ or without previous
exposure to the drug, hypotensive patients who are at
Lisinopril Initial dose: 2.5 mg PO 24 hrly immediate risk of cardiogenic shock
Maintenance dose: 5-20 mg PO • Check BP, renal function & electrolytes 1-2 wk after
24 hrly each dose increment, at 3 mth then every 6 mth
Max dose: 40 mg/day
- More frequent monitoring is necessary in patients
Perindopril Initial dose: 2-2.5 mg PO 24 hrly w/ previous or existing renal dysfunction
Maintenance dose: 4-5 mg PO • NSAIDs should be avoided since they can block the
24 hrly beneficial effects & increase adverse effects of ACE
Quinapril Initial dose: 5 mg PO 12-24 hrly inhibitors & may synergistically compromise renal
Maintenance dose: 10-40 mg/day function
PO divided 12 hrly
Max dose: 40 mg/day
Ramipril Initial dose: 1.25 mg PO 24 hrly
Adjust dose gradually according
to response
Doses ≥2.5 mg/day may be given
24 hrly or divided 12 hrly
Max dose: 10 mg/day
Trandolapril Initial dose: 0.5 mg PO 24 hrly

to response
Max dose: 4 mg/day

B115
Dosage Guidelines
ADRENERGIC AGONISTS
Drug Dosage Remarks
Dobutamine Initial dose: Adverse Reactions

2.5-10 mcg/kg/min IV • CV effects (dose-related increases in heart rate & BP, ectopic
May be adjusted beats, angina/chest pain, palpitations)
according to symptoms, - Reduce dose if the above occur or stop temporarily
diuretic response or • Other CV effects (rarely ventricular tachycardia, occasionally
hemodynamic hypotension which may respond to decrease in dose); Other
monitoring occasional effects (dyspnea, headache, N/V, leg cramps,
Dose range: paresthesia)
0.5-40 mcg/kg/min IV Special Instructions
Max dose: • Hypovolemia should be corrected prior to treatment
40 mcg/kg/min
• Avoid in patients w/ marked obstruction (eg idiopathic
subaortic stenosis, severe valvular stenosis), atrial fibrillation,
atrial flutter & hypersensitivity to sulfites
• Use w/ caution in patients w/ acute MI & in cardiogenic shock
complicated by severe hypotension
• Tolerance may develop after 72 hr & higher dose may be
needed
• Recommended to decrease dose slowly upon discontinuation
Dopamine Initial dose: Adverse Reactions
2-5 mcg/kg/min IV • CV effects (ectopic beats, tachycardia, palpitations, anginal
infusion pain, hypotension, vasoconstriction); Other effects (N/V,
Gradually increase by headache, dyspnea)
5-10 mcg/kg/min • Less common: CV effects (bradycardia, cardiac conduction
Max dose: abnormalities, hypertension may occur if overdosage); Other
20-50 mcg/kg/min effects (piloerection, azotemia)
• Hypovolemia should be corrected prior to treatment
• Avoid in patients w/ pheochromocytoma, hyperthyroidism &
uncorrected tachyarrhythmias or ventricular fibrillation
• Use w/ caution & in low dose in patients w/ shock secondary
to MI, patients w/ history of PVD who are at increased risk of
ischemia of the extremities
• Use w/ caution in patients w/ hypersensitivity to sodium
metabisulfite
• When discontinuing, it may be necessary to gradually decrease
the dose while expanding blood volume w/ IV fluids to prevent
hypotension

B116
Dosage Guidelines
ADRENERGIC AGONISTS (CONT’D)

Drug Dosage Remarks
Epinephrine Hypotension refractory to Adverse Reactions

(Adrenaline) Dopamine/Dobutamine: • CV effects (palpitations, tachycardia, coldness of
0.05-0.5 mcg/kg/min IV infusion extremities, hypertension, vasodilation w/ flushing
Titrate to desired hemodynamic & hypotension); CNS effects (anxiety, restlessness,
effects tremors, weakness, dizziness, headache); Other
effects (sweating, hypersalivation)
• Overdosage or in susceptible subjects: Cardiac
arrhythmias, sharp increase in BP
• Correction of hypovolemia, metabolic acidosis &
hypoxia or hypercapnia should be carried out prior
to administration or concomitantly
• Avoid in patients w/ pheochromocytoma,
arrhythmia, tachycardia >140 bpm, severe
hypertension & narrow-angle glaucoma
• Use w/ caution in patients w/ preexisting
arrhythmias or tachycardia, Prinzmetal’s angina,
thromboembolic disorders, history of ischemic
heart disease, in patients w/ history of occlusive
vascular disease, hypertension, allergy to sodium
metabisulfite, elderly & DM patients
Norepinephrine Initial dose: 0.2-1 mcg/kg/min Adverse Reactions
(Noradrenaline) IV infusion & titrate to desired • CV effects (hypertension, reflex bradycardia,
response peripheral ischemia which may be severe); CNS
effects (headache, weakness, dizziness, tremor,
restlessness, anxiety); Resp effects (resp difficulty,
apnea); Other effects (pallor, intense sweating,
vomiting)
• Severe local adverse effects may occur &
extravasation must be avoided
• Correction of hypovolemia prior to administration
is recommended
• Large vein should be used for IV infusion
• Avoid in the presence of hypertension & monitor
BP closely
• Use w/ caution in patients w/ hypoxia or
hypercapnia, cardiac arrhythmias are more likely in
these patients
• Use w/ caution in hyperthyroidism
• When discontinuing, decrease dose slowly &
observe patient for too rapid fall in BP
- Additional IV fluids may be necessary

B117
Dosage Guidelines
Drug Dosage Remarks
Candesartan Initial dose: 4 mg PO Adverse Reactions
24 hrly • Usually mild & transient: CNS effects (dizziness,
Increase dose at headache); CV effect (dose-related orthostatic hypotension
intervals of 2 wk to which may occur particularly in patients w/ volume
reach the target dose depletion); renal impairment
Max dose: 32 mg/day • Rare other effects: Rash, angioedema, elevated liver
function tests (LFTs); myalgia
Losartan Initial dose: 12.5 mg PO
Titrated at wkly intervals • Patients w/ volume depletion (eg high-dose diuretic
to 12.5 mg, 25 mg, therapy) may experience hypotension & should be started
50 mg, 100 mg PO on low dose
24 hrly up to • Use w/ caution in patients w/ renal artery stenosis, renal
Max dose: 150 mg/day impairment or hepatic impairment, aortic stenosis, mitral
stenosis, obstructive hypertrophic cardiomyopathy,
Valsartan Initial dose: 40 mg PO primary hyperaldosteronism
12 hrly • Contraindicated in patients w/ severe renal or hepatic
May increase to dysfunction & cholestasis
80-160 mg PO 12 hrly at • Check BP, renal function & electrolytes 1-2 wk after each
least at 2-wk interval dose increment, at 3 mth then every 6 mth
Max dose: 320 mg/day - More frequent monitoring is necessary in patients w/
previous or existing renal dysfunction

B118
Dosage Guidelines
BETA-BLOCKERS
Drug Dosage Remarks
Bisoprolol Initial dose: Adverse Reactions

1.25 mg PO 24 hrly x 1 wk • CNS effects (fatigue, depression, dizziness,
If tolerated, increase to 2.5 mg PO 24 hrly headache, confusion, sleep disturbances); CV
x 1 wk effects (heart failure, heart block, coldness of
If tolerated, increase to 3.75 mg PO extremities, male impotence); Resp effects
24 hrly x 1 wk (bronchospasm in susceptible patients & drugs
w/ beta1 selectivity should be used w/ caution
If tolerated, increase to 5 mg PO 24 hrly x in these patients); GI effects (N/V,
4 wk constipation, diarrhea); Metabolic effects (can
If tolerated, increase to 7.5 mg PO 24 hrly produce hyper- or hypoglycemia, changes in
x 4 wk serum cholesterol & triglycerides)
If tolerated, increase to: Special Instructions
Maintenance dose: 10 mg PO 24 hrly • Patients should be on optimal therapy w/ ACE
Carvedilol Initial dose: inhibitors (unless contraindicated) & should
3.125 mg PO 12 hrly x 2 wk be in stable condition without need of IV
inotropic therapy & without signs of marked
If tolerated, increase to 6.25 mg PO fluid retention
12 hrly x 2 wk
• Dose should be titrated individually every 2
If tolerated, increase to 12.5 mg PO wk to maximum dose tolerated by the patient
12 hrly x 2 wk
• During the titration period (increase or
If tolerated, increase to 25 mg PO 12 hrly decrease in dose), monitor patient for heart
Max dose in patients <85 kg: 25 mg PO failure symptoms, fluid retention,
12 hrly hypotension, bradycardia & adjust ACE inhibi-
Max dose in patients ≥85 kg: 50 mg PO tors, diuretics & other drugs as necessary
12 hrly • Patients need to be aware that clinical
Metoprolol 12.5-25 mg PO 24 hrly response to beta-blockers may take 2-3 mth
If tolerated, may titrate dose up to: - If improvement in symptoms does not occur,
Max dose: 200 mg PO 24 hrly beta-blockers should still be continued to
reduce risk of major clinical events
Nebivolol Initial dose: • Contraindicated in severe bradycardia, 2nd- or
1.25 mg PO 24 hrly x 2 wk 3rd-degree of AV block, SA block, sick sinus
If tolerated, increase to 2.5 mg PO 24 hrly syndrome & severe, unstable LV failure or
x 2 wk acute heart failure, hypotension, cardiogenic
If tolerated, increase to 5 mg PO 24 hrly x shock, severe asthma or COPD, late stages of
2 wk peripheral arterial occlusive disease &
If tolerated, increase to 10 mg PO 24 hrly Raynaud’s syndrome, untreated
pheochromocytoma, metabolic acidosis
Max dose: 10 mg/day
• Use w/ caution in patients w/ bronchospasm,
asthma or obstructive airway diseases,
1st-degree AV block, Prinzmetal’s angina,
depression, patients w/ PVD, renal or hepatic
dysfunction, thyrotoxicosis, psoriasis &
patients on Insulin
• Beta-blockers may mask the symptoms of
hyperthyroidism & hypoglycemia & may
aggravate psoriasis
• Patients on long-term treatment should not
discontinue abruptly; should discontinue
gradually over 1-2 wk

& non-elderly adults w/ normal renal & hepatic function unless otherwise stated
B119
Dosage Guidelines
CARDIAC GLYCOSIDES
Drug Dosage Remarks
Digoxin 62.5-250 mcg PO 24 hrly Adverse Reactions
• Side effects are usually due to Digoxin toxicity or
overdosage & Digoxin is usually well-tolerated at the
recommended doses for chronic heart failure
• Digoxin toxicity: GI effects (N/V, anorexia, diarrhea,
abdominal pain) are usually the 1st signs of Digoxin
toxicity; Other signs of toxicity: CNS effects
(headache, fatigue, facial pain, weakness, dizziness,
mental confusion); Visual disturbances (blurred
vision, color disturbances); Toxic doses may cause
serious CV effects (aggravation of heart failure,
arrhythmias, conduction disturbances)
• Hypokalemia can predispose a person to Digoxin
toxicity
• Rarely hypersensitivity reactions occur
• Low doses of Digoxin (62.5 mcg/day or 125 mcg
every other day) should be used in the elderly,
patients w/ impaired renal function or low lean body
mass
Metildigoxin 100-600 mcg PO 24 hrly
(Methyl digoxin) • Avoid in patients w/ obstructive cardiomyopathy
unless there is severe heart failure, in patients w/
Wolff-Parkinson-White (WPW) syndrome or
evidence of accessory pathway
• Contraindicated in patients w/ ventricular
tachycardia, intermittent complete heart block or
2nd-degree AV block
• Use w/ caution in partial heart block, sinus node
disorders, acute myocarditis, acute MI, advanced
heart failure, severe pulmonary disease, thyroid
dysfunction, in patients undergoing
electrocardioversion (withhold Digoxin for 24 hr
prior to procedure) & w/ other drugs that can
depress the sinus or AV nodal function (eg
Amiodarone or beta-blocker)
• Hypokalemia, hypercalcemia, hypomagnesemia,
hypoxia & hypothyroidism may affect the sensitivity
to Digoxin
• Monitoring of Digoxin levels is only necessary if
there is suspected toxicity

B120
Dosage Guidelines
CARDIAC STIMULANTS EXCLUDING CARDIAC GLYCOSIDES

Drug Dosage Remarks
Levosimendan Bolus dose: Adverse Reactions
12 mcg/kg IV over • Effects seen during infusion: CV effect (hypotension); CNS effect
10 min followed by (headache)
Continuous • Less commonly: CV effects (extrasystole, atrial fibrillation,
infusion: tachycardia, palpitations, MI)
0.05-0.2 mcg/kg/ • Effects seen within 3 days after start of infusion: Hematologic effect
min for 24 hr (decreased Hb): Metabolic effect (hypokalemia); CNS effects
Infusion rate may (dizziness, headache); CV effects (hypotension, myocardial
be increased once ischemia, extrasystoles, atrial fibrillation, tachycardia, ventricular
patient is stable tachycardia); GI effects (N/V)
In patients w/ SBP Special Instructions
<100 mmHg, • Contraindicated in patients w/ severe renal or hepatic impairment,
infusion should be significant mechanical obstructions affecting ventricular filling or
started without a outflow or both, severe hypotension & tachycardia, history of
bolus dose to avoid torsades de pointes
hypotension • Use w/ caution in patients w/ mild to moderate renal or hepatic
Individualize dose impairment, in patients w/ ischemic CV disease & concurrent
& length of therapy anemia, in patients w/ hypotension, tachycardia or atrial fibrillation
based on patient w/ rapid ventricular response
response • Monitor serum K levels & correct low K levels prior to therapy
• Correct hypovolemia before starting therapy
• Monitor heart rate x at least 3 days after the end of infusion or
until the patient is clinically stable (5 days is recommended in those
w/ mild-moderate hepatic impairment)
DIRECT VASODILATOR
Drug Dosage Remarks
Sodium Initial dose: Adverse Reactions
nitroprusside 0.3 mcg/kg/min • Adverse effects are typically either due to hypotensive effects or
(Na May increase in from excessive cyanide accumulation (thiocyanate toxicity)
nitroprusside, increments up to • These effects may be reduced w/ a decrease in infusion rate: GI effects
Nitroprusside) 5 mcg/kg/min (N/V, abdominal pain); CNS effects (apprehension, headache,
Adjust dose dizziness, restlessness); CV effects (retrosternal discomfort,
depending on palpitations); Other effects (perspiration, muscle twitching)
hemodynamic • Excessive cyanide may result in: Tachycardia, sweating,
effect or hyperventilation, arrhythmias & metabolic acidosis;
appearance of methemoglobinemia may also occur
headache or nausea • Thiocyanate may cause: Tinnitus, miosis, hyperreflexia, confusion,
Usual dose: hallucinations & convulsions have been reported
3 mcg/kg/min Special Instructions
Max dose: • BP, venous oxygen concentration & acid-base balance should be
10 mcg/kg/min monitored closely
Infusion faster • Avoid extravasation
than 2 mcg/kg/min • Avoid in compensatory hypertension
generates cyanide • Use w/ caution or not at all in hepatic impairment & in patients w/
faster than a low plasma cobalamin concentration or Leber’s optic atrophy
patient can handle • Use w/ caution in patients w/ impaired cerebrovascular circulation,
patients w/ hypothyroidism, renal impairment, ischemic heart
disease & impaired pulmonary function

• If continued for longer than 72 hr, plasma concentrations of
cyanide should be monitored
• When discontinuing, reduce dose slowly

B121
Dosage Guidelines
DIURETICS
Drug Dosage Remarks
Aldosterone Antagonists
Eplerenone Initial dose: 25 mg PO 24 hrly Adverse Reactions
May increase dose to 50 mg • CNS effects (headache,dizziness, drowsiness, ataxia,
within 4 wk mental confusion); GI effects (cramps, diarrhea,
Max dose: 50 mg/day abdominal pain, elevated liver enzymes); CV effect
(angina); Endocrine & metabolic effects
(gynecomastia, hirsutism, menstrual irregularities,
impotence, mild acidosis, hyponatremia,
hyperkalemia, increased uric acid, & transient
increases in BUN); Resp effect (cough); Dermatologic
effects (rash, angioneurotic edema)
• Prior to initiation of therapy verify that eGFR
≥30 mL/min/1.73 m2, creatinine ≤2.5 mg/dL (men) or
≤2 mg/dL (women) & serum K ≤5 mEq/L
Spironolactone Initial dose: 12.5-25 mg PO • Closely monitor serum K & renal function 3 days
24 hrly after initiating therapy, at 1 wk after initiation, at
least mthly for the 1st 3 mth of treatment, then every
Max dose: 50-100 mg/day 3 mth thereafter
• Avoid in patients w/ hyperkalemia, severe renal
impairment, or Addison’s disease
• Use w/ caution in patients at increased risk of
developing hyperkalemia (eg DM, elderly, patients w/
renal or hepatic impairment)

B122
Dosage Guidelines
DIURETICS (CONT’D)
Drug Dosage Remarks
Loop Diuretics
Bumetanide 1-2 mg IM or IV inj given over 2 min Adverse Reactions
May repeat in 20 min if needed • Endocrine & metabolic effects
or (hypomagnesemia, hyponatremia,
IV infusion: 2-5 mg IV in 500 mL hypokalemia & hypochloremic alkalosis
saline over 30-60 min especially after large doses or prolonged
administration, hyperglycemia, glycosuria,
May be repeated in 2-3 hr if necessary hyperuricemia & may precipitate gout)
or • Signs of electrolyte imbalances: Headache,
Initial dose: 1 mg PO 24 hrly muscle cramps, dry mouth, hypotension,
Give 2nd dose 6-8 hr later if thirst, weakness, drowsiness, etc
necessary • Less common other effects (blurred vision,
High doses may be given 8-12 hrly dizziness, orthostatic hypotension, skin rashes
Max dose: 10 mg/day & hypersensitivity reactions, tinnitus)
Furosemide Pulmonary edema Special Instructions
(Frusemide) Initial dose: 20-40 mg slow IV over • Avoid in patients w/ anuria or in renal
1-2 min insufficiency caused by nephrotoxic or
hepatotoxic drugs or caused by hepatic coma
If no adequate response within 1 hr,
may give 80 mg via infusion • Contraindicated in patients w/ severe
electrolyte depletion, hypersensitivity to
or sulfonamides & Furosemide, Addison’s disease
Initial dose: 20-80 mg PO 12-24 hrly • Use w/ caution in patients w/ existing or at a
Max dose: 600 mg/day risk of fluid & electrolyte imbalances, prostatic
Torasemide 10-20 mg IV slow inj over 2 min hyperplasia, impairment of micturition & gout
(Torsemide) If inadequate response, may repeat • Patients w/ hepatic cirrhosis are more likely to
every 2 hr & may double the dose develop hypokalemia & patients w/ severe
Max dose: 200 mg/day heart failure are more likely to suffer
hyponatremia
or
• Monitor patient’s BP, renal function &
5 mg PO 24 hrly electrolytes after initiation & during dose
May increase to 20 mg PO 24 hrly if titration
necessary
Max dose: 40 mg/day

B123
Dosage Guidelines
Drug Dosage Remarks
Amiloride Patient on ACE inhibitor Adverse Reactions
Initial dose: 2.5 mg PO 24 hrly • Endocrine & metabolic effects (hyperkalemia
Max dose: 20 mg/day especially in the elderly, patients w/ DM & patients
Patient not on ACE inhibitor w/ impaired renal function, hyponatremia has
occurred in patients receiving combination diuretic
Initial dose: 5-10 mg PO therapy); GI effects (N/V, abdominal pain, diarrhea,
24 hrly constipation, thirst); CNS effects (headache,
Max dose: 20 mg/day dizziness, weakness, muscle cramps, paresthesia);
CV effect (orthostatic hypotension); Dermatologic
effects (rash, pruritus)
• Use only if hypokalemia persists after the start of
ACE inhibitors & other diuretics
Triamterene Patient on ACE inhibitor • Avoid in patients w/ hyperkalemia or severe renal
Initial dose: 25 mg PO 24 hrly impairment
Max dose: 100 mg/day • Use w/ caution in patients at increased risk of
Patient not on ACE inhibitor developing hyperkalemia (eg DM, elderly, patients w/
renal or hepatic impairment)
Initial dose: 100 mg PO 12 hrly
• Use 1 wk low dose & check serum K & Cr after 5-7 days
of therapy & titrate dose as required
- Continue to recheck serum K & Cr every 5-7 days
until K values are stable
- Monitor serum electrolytes regularly
• Discontinue for at least 3 days before glucose
tolerance tests are done

B124
Dosage Guidelines
Drug Dosage Remarks
Thiazides & Related Diuretics
Bendroflumethiazide Initial dose: Adverse Reactions
5-10 mg PO 24 hrly or on • CV effects (postural hypotension, venous
alternate days thrombosis); Endocrine & metabolic effects (volume
Maintenance dose: depletion, electrolyte imbalance, gout,
2.5-10 mg PO 1-3 times hyperglycemia, altered lipid concentrations); CNS
wkly effects (lethargy, drowsiness, dizziness, syncope,
vertigo, paresthesia); Dermatologic effects
Max dose: 20 mg/day (hypersensitivity reactions, photosensitivity); GI
Hydrochlorothiazide Initial dose: effects (N/V, dry mouth, diarrhea, constipation,
25 mg PO 24 hrly pancreatitis, intrahepatic cholestasis); Hematologic
Maintenance dose: effect (blood dyscrasia); GU effect (impotence);
Musculoskeletal effects (muscle cramps, joint pain)
• May cause hypokalemia, exacerbate SLE & aggravate
Indapamide Initial dose: DM & gout
2.5 mg PO 24 hrly • Use w/ caution in patients w/ hepatic & renal
May increase to 5 mg PO impairment, porphyria, existing electrolyte
24 hrly after 1 wk if disturbance, hepatic cirrhosis, severe heart failure,
necessary hyperlipidemia, extrasystole
Max dose: 5 mg/day • Avoid in patients w/ severe renal & hepatic
impairment, symptomatic hyperuricemia,
Metolazone Initial dose: sulfonamide allergy, Addison’s disease & refractory
2.5 mg PO 24 hrly hypokalemia, hyponatremia, hypercalcemia
May increase to 20 mg PO • Monitor for signs of fluid & electrolyte imbalance
24 hrly
Max dose: 80 mg/day
Vasopressin Antagonist
Tolvaptan Usual dose: Adverse Reactions
15 mg PO 24 hrly • GI effects (dry mouth, constipation); Endocrine
May increase to 30 mg PO effects (thirst, polyuria, hyperglycemia)
24 hrly after at least 24 hr Special Instructions
For patients w/ serum Na • Assess serum Na concentration & neurologic status
<125 mEq/L or for whom especially during initiation & after titration
rapid volume decrease is • Carefully monitor patient’s fluid intake, urine
considered volume, serum Na level & for occurrence of clinical
inappropriate: symptoms (eg thirst, dehydration)
Start w/ 7.5 mg PO 24 hrly • Contraindicated in cases of urgent need to raise
Max dose: 60 mg/day serum Na acutely, in hypernatremia, in patients
Max duration of therapy: unable to autoregulate fluid balance
30 days • Discontinue treatment if serum Na is increased
above normal range, if significant signs & symptoms
of dehydration & hypovolemia are present
• Use w/ caution in hyperkalemia or drugs that
increase serum K, co-administration w/ hypertonic
saline solutions

B125
Dosage Guidelines
NITRATES (IV)
Drug Dosage Remarks
Glyceryl Initial dose: 5-25 mcg/min IV Adverse Reactions

trinitrate May increase dose by 5-10 mcg/min • IV administration (especially if given too
(Nitroglycerin, at 3- to 5-min intervals as required rapidly): May cause CV effects (severe
GTN, NTG) to reach hemodynamic & clinical hypotension, retrosternal discomfort,
response palpitations, tachycardia, flushing); GI effects
Max dose: 200 mcg/min (nausea & retching, abdominal pain); CNS
effects (apprehension, restlessness, muscle
twitching, syncope); Other effect (diaphoresis);
prolonged administration has been associated
w/ methemoglobinemia
• Nitrate-free interval is recommended in
patients on long-term therapy w/ nitrates to
decrease the risk of nitrate tolerance
• Avoid in patients w/ severe hypotension,
hypovolemia, marked anemia, heart failure,
hypertrophic obstructive cardiomyopathy,
Isosorbide Initial dose: 1 mg/hr IV increased cerebral hemorrhage or head trauma, low
dinitrate up to 10 mg/hr cardiac output secondary to hypovolemia,
inferior MI w/ right ventricular involvement,
Max dose: 20 mg/hr
raised intracranial pressure
• Use w/ caution in patients w/ severe renal or
hepatic dysfunction, hypothyroidism,
malnutrition, hypothermia, cerebrovascular
disease, lung disease or cor pulmonale, mitral
valve prolapse, cardiac tamponade, glaucoma
• Close monitoring of heart rate & BP is
necessary during IV infusion
• Slow or temporarily stop infusion if mean
arterial BP falls below 80 mmHg or SBP falls
<90 mmHg
• Gradual withdrawal in patients who have
received prolonged high dose infusions
• Do not administer to patients who have taken
phosphodiesterase inhibitors within the past
24 hr
• The plastic used for administration may absorb
GTN & dosing may need to be adjusted for this

B126
Dosage Guidelines
NITRATES (ORAL)
Glyceryl 400, 500, 600 mcg 400-600 mcg SL Adverse Reactions

trinitrate sublingual (SL) every 5 min until • CNS effects (headache, lightheadedness,
(Nitroglycerin, tab cessation of pain or dizziness, syncope, vertigo, restlessness,
GTN, NTG) side effects occur confusion); rarely CV effects (tachycardia,
Max dose: 3 doses hypotension, flushing, palpitation); GI
within 15 min effects (N/V, bowel incontinence,
400 mcg/dose SL 1-2 sprays xerostomia)
spray (400-800 mcg) SL, Special Instructions
closing the mouth • Nitrate-free interval is recommended in
after spraying patients on long-term therapy w/ nitrates
Max dose: 3 doses to decrease the risk of nitrate tolerance
within 15 min • Avoid in patients w/ severe hypotension,
hypovolemia, marked anemia, heart failure
Isosorbide 5 mg, 10 mg SL 5-10 mg SL every
due to obstruction or raised intracranial
dinitrate tab 2-3 hr until
pressure due to head trauma or
cessation of pain or
hemorrhage
side effects occur
• Use w/ caution in patients w/ severe renal
or
or hepatic dysfunction, hypothyroidism,
30-160 mg PO daily malnutrition, mitral valve prolapse,
in divided doses arterial, hypoxemia, glaucoma or
Max dose: hypothermia
240 mg/day PO • Co-administration w/ phosphodiesterase
20 mg retard tab 20 mg PO 12 hrly inhibitors (eg Sildenafil) are
contraindicated within 24 hr interval after
1.25 mg/dose 1-3 sprays taking a nitrate preparation
buccal spray (1.25-3.75 mg) into Acute attacks
the buccal cavity;
waiting 30 sec • Instruct patient to sit down & use
between sprays medication at 1st sign of angina attack
Do not inhale • Patient should be made aware that dose
medication may be repeated in 5-10 min w/ max of
3 doses given
• Patient should seek emergency medical
treatment if pain does not subside

B127
Dosage Guidelines
PERIPHERAL VASODILATOR & CEREBRAL ACTIVATOR

Drug Dosage Remarks
Nesiritide Initial loading dose: Adverse Reactions

2 mcg/kg IV inj over 1 min • CV effects (hypotension, angina); CNS effects
followed immediately by (dizziness, headache, anxiety, insomnia); GI effects
maintenance infusion (N/V, abdominal pain)
Maintenance dose: Special Instructions
0.01 mcg/kg/min as continuous • Contraindicated in cardiogenic shock (when used
infusion as a primary therapy) & in hypotension (SBP
<90 mmHg)
• Not recommended in patients w/ known or
suspected low cardiac filling pressures or in whom
vasodilating agents are inappropriate (eg restrictive
or obstructive cardiomyopathy, pericardial
tamponade, significant valvular stenosis,
constrictive pericarditis)
• Monitor BP closely during administration
• Stop or reduce dose if hypotension occurs during
infusion
PHOSPHODIESTERASE INHIBITORS
Drug Dosage Remarks
Amrinone Initial dose: Adverse Reactions

(Inamrinone) 750 mcg/kg by slow IV inj over • CV effects (hypotension, supraventricular
2-3 min arrhythmia, ventricular arrhythmia, chest pain,
May be repeated after 30 min if vasculitis); CNS effects (headache, tremor); GI
necessary effects (N/V); Metabolic effect (hypokalemia); Resp
Maintenance dose: effect (bronchospasm); Other effects (fever, nail
discoloration, hypersensitivity, myositis)
5-10 mcg/kg/min IV infusion
• Produces dose-dependent thrombocytopenia
Max dose: 10 mg/kg/24 hr
• Long-term use may cause hepatotoxicity
Enoximone Initial dose: Special Instructions
0.5-1 mg/kg slow IV bolus over • Monitor BP, heart rate, platelet count & liver
5-10 min followed by function tests (LFTs)
Maintenance dose: • Maintain fluid & electrolyte balance
5-20 mcg/kg/min IV infusion • Contraindicated in patients w/ heart valve stenosis
Adjust according to clinical & & acute MI
hemodynamic response • Use w/ caution in patients w/ severe obstructive
Milrinone Initial dose: aortic or pulmonary vascular disease, hypertrophic
25-75 mcg/kg slow IV bolus over cardiomyopathy, atrial flutter or fibrillation
10 min followed by
Maintenance dose:
0.375-0.75 mcg/kg/min IV infusion
Titrate according to hemodynamic
& clinical response
Max dose: 1.13 mcg/kg/24 hr

B128
Heart Failure - Chronic (1 of 29)
1
Patient presents w/ or without signs &
symptoms but w/ risk of heart failure (HF)
2
DIAGNOSIS No ALTERNATIVE
Is HF confirmed?
DIAGNOSIS
Yes
CONSIDER EXPERT REFERRAL

• Determine etiology & initiate
appropriate therapy including
revascularization
MANAGEMENT
STAGE A STAGE B STAGE C

At risk for HF Pre-HF HF
A Non-pharmacological A Non-pharmacological
therapy therapy
TREATMENT
B Pharmacological B Pharmacological therapy See next page
therapy • Prevention of CV events
• Control of risk & - Angiotensin-converting
prevention of enzyme (ACE) inhibitor
cardiovascular (CV)
- Angiotensin receptor blocker
events
(ARB, if intolerant of ACE
• Evaluation by inhibitor)
multidisciplinary
team for - Beta-blocker
management of C Interventional therapy
patient w/ • Device-based therapy
cardiotoxin exposure - Implantable cardioverter-
defibrillator (ICD)
B129
HEART FAILURE - CHRONIC
STAGE C
HF
ASSESS LEFT VENTRICULAR

EJECTION FRACTION (LVEF)
LVEF LVEF LVEF

≤40% 41-49% ≥50%
A Non-pharmacological therapy A Non-pharmacological therapy

B Pharmacological therapy1 B Pharmacological therapy
• Angiotensin receptor-neprilysin • Diuretics (as needed)
inhibitor (ARNI) (NYHA Class II-III); • SGLT2 inhibitor
ACE inhibitor or ARB (NYHA Class • ACE inhibitor/ARB/ARNI
II-IV)2 • Beta-blocker3
• Beta-blocker3 • MRA
• Mineralocorticoid receptor antagonist Control risk & triggering
(MRA)/aldosterone antagonist factors, manage comorbid
• Sodium-glucose linked transporter/ conditions
co-transporter 2 (SGLT2) inhibitor
• Diuretics (as needed if w/ fluid
retention)
If w/ persistent symptoms: A Non-pharmacological therapy

B
• Hydralazine & Isosorbide dinitrate Pharmacological therapy
C • Diuretics (as needed)
Interventional therapy
• SGLT2 inhibitor
• Device-based therapy
• ARB4
- Eg cardiac resynchronization therapy
• ARNI4
(CRT), ICD
Additional treatment (if indicated): • MRA4
• Diuretics (titrate dose if already on) Control risk & triggering
• Ivabradine factors, manage comorbid
conditions
• Digoxin
- Should be considered for all HF patients
w/ atrial fibrillation (AF) & low BP
• Vericiguat
Stage D
Advanced HF
• Device-based therapy
- Eg mechanical circulatory support w/ left
ventricular assist device (LVAD)
• Surgery
- Eg coronary revascularization [coronary
artery bypass grafting (CABG) or
percutaneous coronary intervention (PCI)],
valvular surgery, heart transplantation
Patient counselling
• Discuss end-of-life issues & palliative care
1Medications listed may be initiated simultaneously at initial low doses or sequentially.

2Consider ACE inhibitor or ARB in patients w/ inaccessibility, intolerance or contraindications to ARNI.
3Evidence-based beta-blockers: Bisoprolol, Carvedilol or Metoprolol succinate
4Patients w/ LVEF nearer to 50% will have greater benefit.
B130

1 CHRONIC HEART FAILURE
Heart Failure (HF)
• Clinical syndrome due to a structural or functional cardiac disorder that impairs the ability of the ventricle to
fill w/ or eject blood in order to deliver oxygen at a rate commensurate w/ the requirements of the metabolizing
tissues in spite of normal filling pressures or only at the expense of elevated filling pressures
• Symptoms are caused by ventricular dysfunction secondary to abnormalities of the myocardium, pericardium,
endocardium, valves, heart rhythm or conduction
Common Causes of Heart Failure
• Cardiac pathologies [eg coronary artery disease (CAD), cardiomyopathies, congenital heart disease,
tachyarrhythmia, valvular heart disease]
• Hypertension
• Infiltrative cardiac diseases (eg amyloid, hemochromatosis, sarcoid)
• Infections (eg rheumatic fever, sexually transmitted diseases, pneumonia)
• Endocrine disorders (eg diabetes, dyslipidemia, hypo/hyperthyroidism, adrenal disorder, pheochromocytoma)
• Nutritional disorders (eg deficiency of thiamine, selenium, iron, calcium, phosphates & L-carnitine, obesity,
cachexia)
• Toxins (eg alcohol, medications, trace elements, illicit drug use eg cocaine, cannabis, methamphetamine)
• Drugs [eg beta-blockers, calcium antagonists, antiarrhythmics, cardiotoxic chemotherapy agents, nonsteroidal
anti-inflammatory drugs (NSAIDs), non-compliance to medications]
• Other diseases (eg inflammatory/immunological diseases, neuromuscular disease, malignancies, severe anemia,
renal dysfunction, renal artery stenosis & end-stage renal failure)
Types of Heart Failure
Heart Failure Based on Time-course
• Acute heart failure (AHF)
- Refers to the first occurrence (new-onset or de novo) of HF
- May result from the deterioration of a previously stable HF
• Chronic heart failure (CHF)
- A chronic state where patient’s signs & symptoms have been unchanged (stable) for at least a month
- May decompensate suddenly or slowly when stable CHF deteriorates leading to hospitalization or outpatient
IV diuretic therapy
• Congestive heart failure
- Refers to AHF or CHF that has evidence of volume overload
• Transient heart failure
- Refers to symptomatic HF over a limited period of time, although long-term therapy may be indicated
- Recurrent or episodic
Heart Failure Based on Left Ventricular Ejection Fraction (LVEF)
• Heart failure w/ preserved EF (HFpEF) (diastolic HF)
- W/ preserved systolic function; EF is defined as ≥50%
• Heart failure w/ reduced EF (HFrEF) (systolic HF)
- EF is defined as ≤40%
• Patients w/ an EF in the 41-49% range represent a ‘grey area’ & it is termed HF w/ mildly reduced EF (HFmrEF)
• Further criteria for the diagnosis of HF w/ preserved & mildly reduced EF include presence of HF symptoms
&/or signs, elevated levels of natriuretic peptides w/ at least 1 added criterion of either significant structural
heart disease or diastolic dysfunction
Presentation of Patients w/ Heart Failure
Decreased Exercise Tolerance
• Dyspnea &/or fatigue occurring at rest or during exercise
• Impaired exercise tolerance not noticed by patient as it occurs gradually
Fluid Retention
• Complaints of leg or abdominal swelling as primary symptom
No Symptom or Symptoms of Another Cardiac or Other Disease
• Cardiac enlargement or dysfunction may be noted during their evaluation for a disease other than HF
B131
1 CHRONIC HEART FAILURE (CONT’D)

Development Stages of Heart Failure
Stage A
• At risk for HF but without structural or functional heart disease or signs or symptoms of HF
- Abnormal cardiac biomarkers are absent
- Hypertension, atherosclerotic cardiovascular disease, diabetes , obesity, metabolic syndrome
- Use of cardiotoxins
- Family history of or genetic variant for cardiomyopathy
Stage B
• Structural or functional heart disease but without signs or symptoms of HF
- Previous myocardial infarction (MI), left ventricular (LV) remodelling including left ventricular hypertrophy
(LVH) & low EF, asymptomatic valvular disease
- Elevated levels of natriuretic peptide or cardiac troponin in the setting of cardiotoxin exposure
Stage C
• Structural &/or functional heart disease w/ prior or current signs &/or symptoms of HF
- Persistent HF or HF in remission
- Shortness of breath (SOB), fatigue & decreased exercise tolerance
Stage D
• Refractory, advanced or end-stage HF
- Marked signs &/or symptoms at rest despite guideline-directed medical treatment (GDMT) (refractory or
intolerant to GDMT), recurrent hospitalizations
- Requires specialized treatment interventions
2 DIAGNOSIS
• Requires a thorough history & physical examination, identification of the etiology & risk factors, & diagnostic
examination of the cardiac structure & function in order to identify diseases that will require specific
management
History
• Many symptoms of HF are nonspecific & do not distinguish between HF & other diseases
• More Specific Symptoms
- Dyspnea at rest or on exertion/breathlessness
- Paroxysmal nocturnal dyspnea
- Orthopnea
- Reduced exercise capacity
- Fatigue/longer time to recover post exercise
- Edema/ankle swelling
• Less Specific Symptoms
- Nocturnal cough
- Wheezing
- Palpitations
- Dizziness
- Bendopnea
- Bloated feeling
- Anorexia
- Confusion (especially in the elderly)
- Depression
- Syncope
• Determine predisposition to risk factors especially in lifestyle (eg smoking, diet, alcohol consumption, substance
abuse & inactivity)
• Review the past medical history
- To identify possible cause of HF & presence of comorbid illnesses (eg history of CAD or arterial hypertension,
previous cardiac surgery, chronic lung, liver or kidney disease, COVID-19 infection)
- Screening HF patients for CV & non-CV comorbidities help alleviate symptoms & improve prognosis
- Current or past standard or alternative therapies & chemotherapy (eg diuretic use, exposure to radiation or
cardiotoxic drug)
• Family history to determine familial predisposition to atherosclerotic disease, cardiomyopathy (obtain a
3-generation family history), conduction system disease or tachyarrhythmias
B132

Physical Exam
More Specific Signs
• S3 gallop
• Laterally displaced or prominent apical impulse
• Elevated jugular venous pressure (JVP)
• Hepatojugular reflux
Less Specific Signs
• Irregular pulse
• Tachycardia w/ pulsus alternans
• Narrow pulse pressure
• Murmurs/S4 gallop
• Pulmonary rales or crepitations
• Reduced air entry or dullness at lung bases
• Tachypnea/orthopnea
• Weight gain (>2 kg/week)
• Weight loss (in advanced HF)
• Oliguria
• Other findings (eg hepatomegaly, ascites, peripheral edema/bilateral ankle edema, cold extremities, cachexia)
Assessment of Volume Status
• Determines the need for diuretic treatment
• Detects sodium excess or deficiency that may affect efficacy & reduce tolerability of drugs used to treat HF
• At each visit, record the patient’s weight, vital signs especially blood pressure (BP) (sitting & standing) & other
abnormal physical findings including presence of clinical congestion
Assessment of Functional Capacity
New York Heart Association (NYHA) Functional Classification in Patients w/ Heart Failure
• Class I
- Patient has no limitation of physical activity
- Ordinary physical activity does not cause symptoms (eg palpitation, dyspnea or fatigue)
• Class II
- Patient has slight limitation of physical activity
- Comfortable at rest but ordinary physical activity produces symptoms
• Class III
- Patient has a marked limitation of physical activity
- Comfortable at rest but less than ordinary activity causes symptoms
• Class IV
- The patient is unable to carry out any physical activity without discomfort
- HF symptoms are present at rest & any physical activity will cause an increase in discomfort
Laboratory/Diagnostic Tests
• Lab testing will confirm the presence of HF & may show the presence of disorders that can lead to or exacerbate
HF & may help guide appropriate management
• Patients w/ HFpEF are recommended to have screening for & treatment of etiologies & CV & non-CV
comorbidities
• For the diagnosis of HFpEF & HFmrEF, spontaneous or provokable increased LV filling pressures should be
confirmed in patients w/ LVEF >40% via elevated levels of natriuretic peptides, diastolic function on
echocardiography or invasive hemodynamic measurement
- Additional findings supporting an HFpEF diagnosis include an increase in the LV mass index &/or left atrial
volume index
B133
Laboratory/Diagnostic Tests (Cont’d)
Tests to Consider in All Patients
• Initial evaluation includes, but is not limited to, the following:
- Complete blood count (CBC), serum electrolytes (include sodium, potassium, calcium & magnesium), blood
urea nitrogen (BUN), creatinine/estimated glomerular filtration rate (eGFR), albumin, cardiac enzymes, liver
enzymes, bilirubin, serum ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), blood
lipids, blood glucose, international normalized ratio (INR), C-reactive protein (CRP), thyroid function &
urinalysis
- Used to detect reversible/treatable causes of HF & comorbidities interfering w/ HF
- Natriuretic peptides [B-type natriuretic peptide (BNP) ≥35 pg/mL, N-terminal pro B-type natriuretic peptide
(NT-proBNP) ≥125 pg/mL or mid-regional atrial natriuretic peptide (MR-proANP)]
- Useful for differentiating dyspnea caused by HF from dyspnea due to other causes
- Used in patients in whom the diagnosis of HF is uncertain & when an echocardiogram cannot be performed
- Also helpful in establishing disease severity, stratifying risk & obtaining prognostic information
- Recommended biomarker to be used to screen high-risk patients for HF
• 12-Lead Electrocardiogram (ECG)
- Most common findings are nonspecific repolarization abnormalities (ST-T wave changes)
- Abnormalities are usually nonspecific (include LV hypertrophy, Q wave, sinus tachycardia & AF)
- Conduction abnormalities may also be seen [eg left bundle branch block (LBBB), first-degree atrioventricular
(AV) block, left anterior hemiblock & nonspecific intraventricular conduction delays]
- Information obtained can assist in treatment planning & is of prognostic importance
- Normal ECG makes the diagnosis of HF due to LV systolic dysfunction less likely
• Chest radiography (X-ray)
- Useful to determine the heart size, presence of pulmonary congestion, detection of pulmonary & other
diseases & proper placement of implanted cardiac device
- Normal chest X-ray does not exclude the diagnosis of HF
- Common abnormal findings are pulmonary venous redistribution w/ upper lobe blood diversion
• Transthoracic echocardiography
- Most useful initial investigation performed immediately to confirm the diagnosis in patients suspected w/
HF
- Evaluates cardiac structure & function (eg chamber volumes/sizes, LV systolic function by LVEF, diastolic
function, hemodynamics, wall thickness & valvular structure & function), assists in treatment management
& obtains prognostic information
- Excludes correctable causes of HF
Tests to Consider in Selected Patients
• Cardiac magnetic resonance imaging (CMRI)
- Performed in select patients, it evaluates cardiac structure & function, measures LVEF, assesses myocardial
scarring, characterizes cardiac tissue especially in patients w/ inadequate echocardiographic images or where
there are inconclusive or incomplete echocardiographic findings
- Useful in the work-up of patients suspected w/ cardiomyopathy, arrhythmias, cardiac tumors or cardiac
involvement by a tumor, pericardial disease & complex congenital heart disease
• Coronary angiography
- Recommended in patients w/ angina pectoris despite medical therapy or symptomatic ventricular arrhythmias
who are suitable for coronary revascularization to evaluate the coronary anatomy (ie establishes the presence
& extent of CAD)
- Also considered in patients w/ evidence of reversible myocardial ischemia on non-invasive testing, especially
if the EF is decreased
- A multidetector computed tomography (MDCT) study may be used as an alternative to invasive coronary
angiography in select patients to rule out significant CAD
• Cardiac catheterization
- Considered in patients who are being evaluated for heart transplantation or mechanical circulatory support
- Evaluates the cardiac function & pulmonary arterial resistance
- May be performed in cases of uncertain diagnosis, eg early HFpEF
- A right heart catheterization should be considered in patients in whom HF is thought to be caused by
congenital heart disease, constrictive pericarditis, restrictive cardiomyopathy & high output states
- May be considered to determine patient’s volume status
B134

Laboratory/Diagnostic Tests (Cont’d)
Tests to Consider in Selected Patients (Cont’d)
• Myocardial perfusion/ischemia imaging [eg stress echocardiography, CMRI, single photon emission computed
tomography (SPECT) or positron emission tomography (PET)]
- Alternative imaging modality in patients w/ unsatisfactory echocardiographic findings or when the degree
of LVEF influences treatment management
- Considered in patients who are suspected to have CAD & who are suitable for coronary revascularization
• Cardiopulmonary exercise testing
- Detects reversible myocardial ischemia & investigates the cause of dyspnea
- Used in the objective evaluation of exercise & functional capacity & exertional symptoms to aid in prescribing
an exercise training program
- Also used for evaluating patients for heart transplantation &/or mechanical circulatory support & to obtain
prognostic information
- An alternative option to measure patient’s exercise capacity is the 6-minute walk test
• Endomyocardial biopsy
- May be useful in identifying a specific diagnosis which would influence treatment decisions
- May be indicated rarely in patients w/ dilated cardiomyopathy w/ recent onset of symptoms & where HF has
been excluded by angiography & in primary myocardial diseases like endomyocardial fibrosis & amyloid
heart disease
- May also be used in patients w/ rapidly progressive clinical HF or ventricular dysfunction despite appropriate
medical treatment & those who are suspected of having myocarditis or infiltrative diseases (eg amyloidosis)
• Spirometry & pulmonary function tests
- Assess the potential contribution of lung disease to the patient’s dyspnea
- Demonstrate or exclude concomitant smoking-related or other respiratory causes of airway limitation
Patient Education
General Counseling
• Patient counseling tends to improve patient compliance & outcomes
• Educate the patient & caregivers about CHF
- Discuss the nature of HF, treatment goals, drug regimens & side effects, dietary & activity restrictions, device
management, signs & symptoms of worsening HF, what to do if these symptoms occur & prognosis
• Advise patient regarding enrollment in a multidisciplinary HF management program, self-management strategies
& either home-based &/or clinic-based programs to decrease the risk of hospitalization & mortality
• Provide discharge instructions w/ a transitional care plan & programs for psychological & social support
• Genetic counseling & screening may be advised to patients w/ 1st-degree relatives w/ inherited or genetic
cardiomyopathies
Medications
• Inform patients about the drugs’ indications, dosage, side effects & precautions
• Emphasize the importance of treatment adherence
• Assist patients in dealing w/ complicated drug regimens & in accessing affordable medications
• Avoid NSAIDs including cyclooxygenase-2 (COX-2) inhibitors
- Patients are at increased risk for fluid retention & renal failure especially those w/ decreased renal function
or who are on ACE inhibitors
- NSAIDs can cause sodium retention, peripheral vasoconstriction, decrease the efficacy & increase the toxicity
of ACE inhibitors & diuretics
Weight Monitoring
• Increase in body weight is associated w/ deterioration of HF & fluid retention
• Patients should weigh themselves regularly to monitor weight change
- If a patient has sudden unexpected weight gain of >2 kg in 3 days, the physician should be informed & diuretic
dose may need to be adjusted
• Patients who are obese need to lose weight to decrease symptoms, improve well-being & prevent progression
of HF
• Weight reduction should not routinely be done in patients w/ moderate to severe HF since unintentional weight
loss & anorexia are common problems
• Cardiac cachexia, defined as involuntary non-edematous weight loss ≥6% of total body weight within the
previous 6-12 months, is an important predictor of decreased survival
- Possible treatments are appetite stimulants, exercise, anabolic agents & nutritional supplements
B135
A NON-PHARMACOLOGICAL THERAPY (CONT’D)

Patient Education (Cont’d)
Diet Modification
• Sodium restriction
- Restrict sodium intake to <2 g/day (~1/4 teaspoon of table salt)
• Potassium reduction
- Advise patients regarding a low potassium diet since hyperkalemia &/or abnormal renal function hinders
the ability to reach target medication doses
• Fluid restriction
- Should be individualized, though generally may limit fluid intake to 1-1.5 L/day in patients w/ normal renal
function
- Routine fluid restriction in all patients w/ mild to moderate symptoms is probably not beneficial
- Weight-based fluid restriction (30 mL/kg body weight if body weight ≤85 kg or 35 mL/kg if body weight
>85 kg) may cause less thirst
• Caffeine
- Excessive caffeine intake may increase heart rate, increase BP & exacerbate arrhythmia
- Limit caffeine beverages to 1-2 cups/day
• Saturated fat
- Limit saturated fat intake in all patients w/ HF
• Omega-3 fatty acids
- Supplementation w/ omega-3 polyunsaturated fatty acids is a reasonable adjunctive therapy in CHF NYHA
Class II-IV
- A trial showed reduction in mortality or hospital admission for a CV event
• Fiber
- High fiber diet is recommended to prevent constipation secondary to relative gastrointestinal hypoperfusion
- Helps avoid straining in stool which may provoke angina, dyspnea or arrhythmia
• Frequent small meals may prevent shunting of the cardiac output to the gastrointestinal tract, thus decreasing
the risk of angina, dyspnea, dizziness or bloating
Alcohol
• Alcohol is a direct myocardial toxin & may impair cardiac contractility
• May have negative inotropic effect & may be associated w/ BP elevation & increased risk for arrhythmia
• Advise patient to abstain from or avoid excessive alcohol consumption
• Limit alcohol intake to 10-20 g/day (2 units/day in men or 1 unit/day in women)
- A standard drink of 14 g of pure alcohol is equal to 12 oz of beer (5% alcohol content), 8-9 oz of malt liquor
(7% alcohol content), 5 oz of table wine (12% alcohol content), or 1.5 oz of 80-proof distilled spirits or liquor,
eg gin, rum, vodka, whiskey (40% alcohol content)
- 1 unit is equivalent to 10 mL (8 g) of pure alcohol [⅓ pint of beer (5.2% alcohol content), half a standard glass
(175 mL) of wine (12% alcohol content), or 1 measure (25 mL) of spirits (40% alcohol content)]
Smoking Cessation
• Primary goals: Complete smoking cessation & avoidance of passive smoking
• Provide counseling, cessation programs & pharmacotherapy (eg nicotine replacement, Bupropion)
Physical Activity
• Regular physical activity or aerobic exercise is strongly recommended in patients w/ CHF (NYHA Class I-III)
- It should be individualized based on the patient’s capacity
- Promote adherence to an exercise goal of 30 minutes of moderate activity or exercise, 5-7 days a week w/
warm up & cool down exercise
• When clinically stable, patients should be encouraged to carry out daily physical activities & leisure activities
that do not induce symptoms
Sexual Activity
• Counsel patients to defer sexual activities if they are in NYHA Class III-IV but may resume when their cardiac
condition is stabilized
• Sexual activity is likely to be safe in patients who are able to achieve approximately 5-6 metabolic equivalents
of exercise (ie can climb two flights of stairs without stopping due to angina, dyspnea or dizziness)
• Advise patients regarding the use of sublingual Nitroglycerin as prophylaxis against dyspnea & chest pain
during sexual activity
- Drugs used in erectile dysfunction (eg Avanafil, Sildenafil, Tadalafil) are contraindicated in patients receiving
nitrates or those who have hypotension, arrhythmias or angina pectoris
B136

Patient Education (Cont’d)
Pregnancy & Contraception
• Low-dose oral contraceptives have a small risk of causing hypertension or thrombogenicity, but these risks
need to be weighed against the risk of pregnancy
• Advise patients w/ LVEF <30% & those in NYHA Class III-IV to not get pregnant; if HF occurs during pregnancy,
use beta-blockers, Digoxin, diuretics, Hydralazine &/or nitrates judiciously
• Women w/ a history of HF or cardiomyopathy should be counseled pre-pregnancy regarding contraception
& the risks of CV status deterioration while pregnant
Travel
• Discuss travel plans w/ the physician for patients w/ HF who are at increased risk of deep venous thrombosis
(DVT)
• Air travel is preferred than other means of transportation, especially on long journeys
- Long flights may predispose patients to accidental omission of medicines, edema of the lower extremities,
dehydration & DVT
- DVT prophylaxis w/ a single injection of low-molecular-weight Heparin &/or graduated compression
stockings plus calf stretching during the flight are recommended
- Pharmacotherapy may be added if there is significant risk of DVT
• Avoid high altitude destinations of >1500 meters because of relative hypoxia
• Useful in patients who are clinically stable & able to participate in exercise programs
• Several meta-analyses demonstrated cardiac rehabilitation improves functional capacity, exercise duration &
health-related quality of life & decreases risk of hospitalizations & mortality in HF patients
- An exercise-based cardiac rehabilitation is recommended in symptomatic patients w/ HFrEF who are stable
to decrease risk of hospitalization
- Consider a supervised program in patients w/ frailty, more severe disease or comorbidities
• Helpful in monitoring symptoms & supporting drug titration
• Following revascularization, patients may also be referred for cardiac rehabilitation
Depression & Mood Disorder
• Screening for endogenous or prolonged reactive depression in patients w/ HF should be done following diagnosis
& at periodic intervals as clinically indicated
• Initiate appropriate pharmacotherapy (eg selective serotonin receptor uptake inhibitors) & provide psychosocial
support
Sleep & Breathing Disorders
• Patients w/ symptomatic HF usually have sleep-related breathing disorders (eg central or obstructive sleep
apnea)
• Weight loss in obese patients, smoking cessation & abstinence from alcohol are recommended to decrease the
risks
• Continuous positive airway pressure (CPAP) should be considered in polysomnograph-documented obstructive
sleep apnea to improve daily functional capacity & quality of life
Please see the Heart Failure - Acute disease management chart for information on IV drugs administered
in the hospital/healthcare facility for emergency cases of HF
Control of Risk & Prevention of Cardiovascular Events
Hypertension & Dyslipidemia
• Recommended optimal BP for HF patients w/ hypertension is <130/80 mmHg1; a healthy diet & statin therapy
are potential preventive strategies for dyslipidemia
• Please see Hypertension & Dyslipidemia disease management charts for further information
Diabetes Mellitus (DM)
• SGLT2 inhibitors significantly decrease HF events in type 2 diabetes patients w/ HF, established CV disease or high
risk for CV disease; Metformin may be used in type 2 diabetes patients w/ stable HF
• Long-term treatment w/ ACE inhibitors or ARBs
- ACE inhibitors & ARBs can prevent the development of end-organ disease, CV complications & risk of HF
in patients w/ diabetes & those without hypertension
• Other agents that may also be given to patients w/ DM include a beta-blocker, MRA, an ARNI & Ivabradine
1Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities.
B137

Control of Risk & Prevention of Cardiovascular Events (Cont’d)
Atherosclerotic Disease
• One large-scale trial showed that long-term therapy w/ an ACE inhibitor decreased the risk of CV death, MI
& stroke in patients w/ known vascular disease
• ACE inhibitors prevent HF in patients who are at high risk of developing HF, have a history of atherosclerotic
vascular disease, DM or hypertension w/ associated CV risk factors
• For prevention of symptomatic HF in pre-HF patients, consider the following:
- ACE inhibitor or beta-blocker for LVEF ≤40%
- ARB in patients intolerant of ACE inhibitors & w/ a recent MI & LVEF ≤40%
- Beta-blocker (LVEF ≤40%) or statins for patients w/ a remote or recent history of acute coronary syndrome
or MI
• An ICD may be placed in pre-HF patients who are at least 40 days post-MI w/ LVEF ≤30% & w/ >1 year expected
survival
Treatment Strategy
• The use of ARNI, ACE inhibitor or ARB, beta-blocker, MRA & SGLT2 inhibitor is important in modifying the
course of systolic HF
- Should be considered in all patients w/ HF because it decreases the risk of HF hospitalization & premature
death
- They are commonly used in conjunction w/ a diuretic to relieve the symptoms & signs of congestion
- Initiation of a beta-blocker is better tolerated when the patient is less congested (dry) & an ARNI, ACE
inhibitor or ARB when the patient is congested (wet)
• Titration of therapy to maximally tolerated target doses must be done in chronic HFrEF patients in order to
achieve maximal benefits of GDMT
• GDMT should be continued, initiated & further optimized in hospitalized patients before discharge
• May consider continuous IV inotropes &/or vasopressors as a bridge to mechanical circulatory support or
heart transplantation in patients w/ advanced HF w/ low cardiac output & evidence of organ hypoperfusion,
or as palliative therapy to control symptoms & improve functional status
• In COVID-19 infection, inhibition of the renin-angiotensin-aldosterone system is not associated w/ infection
risk or disease severity & should be continued as long as hemodynamically tolerated by the patient
- CHF patients should continue GDMT regardless of COVID-19 infection
• Recommended for the prevention of HF in patients at risk of this syndrome
• ACE inhibitors should be prescribed to all patients w/ decreased LVEF of ≤40% regardless of symptoms unless
contraindicated or not tolerated
• Started as soon as HF diagnosis is made because of its modest effect on LV remodelling which delays the
development of symptomatic CHF in patients w/ asymptomatic LV dysfunction & those without ventricular
dysfunction
• If a patient has recent or current history of fluid retention, diuretics should be started prior to ACE inhibitors
to ensure sodium balance, preventing peripheral & pulmonary edema
• An increase in the creatinine & potassium levels is expected after treatment w/ an ACE inhibitor (or ARB) or
ARNI
- An increase in the creatinine level of up to 3 mg/dL (eGFR >25 mL/min/1.73 m2) or up to 50% above baseline
(whichever is smaller) & potassium level to ≤5.5 mmol/L is acceptable
- Administration of potassium-lowering agents (eg patiromer & sodium zirconium cyclosilicate) may allow
renin-angiotensin-aldosterone system (RAAS) inhibitor initiation or uptitration in a large number of patients
w/ hyperkalemia; consider a specialist referral if w/ significant renal dysfunction or hyperkalemia
Angiotensin Receptor Blockers (ARBs)/Angiotensin II Antagonists
• Recommended as an alternative in patients who are intolerant of ARNI or ACE inhibitors due to cough or
angioedema; patients should also be given a beta-blocker & an MRA
- Can also be used as alternatives to ACE inhibitors as 1st-line agents in those already on ARB for other
indications
• May also be considered in patients w/ systolic CHF who remain symptomatic despite receiving ACE inhibitor
& a beta-blocker & are intolerant of MRA
• Candesartan may be considered for ambulatory patients w/ symptomatic HFmrEF to decrease the risk of HF
hospitalization & CV death
• Avoid use in patients w/ recent acute MI & decreased LVEF who are on ACE inhibitor & beta-blocker
• Triple combination of ACE inhibitor, ARB & MRA is not recommended due to increased risk of hyperkalemia
B138

• Eg Sacubitril/Valsartan
• Indicated for patients w/ HFrEF (EF ≤40%), NYHA Class II-III
• Acts by inhibiting neprilysin which slows down the degradation of natriuretic peptides, bradykinin & other
peptides leading to high amounts of circulating A-type natriuretic peptide & BNP resulting in diuresis, natriuresis
& relaxation & anti-remodelling of the myocardium
- Interpret BNP values w/ caution as BNP levels may rise w/ ARNI therapy
• Recommended replacement for ACE inhibitor or ARB to further decrease morbidity & mortality in patients
w/ HFrEF NYHA Class II-III
• May consider starting Sacubitril/Valsartan rather than an ACE inhibitor or ARB for patients admitted w/
new-onset HF or decompensated CHF for reduction of short-term risk of adverse events & for simplification
of management (ie the need to initially titrate ACE inhibitor then switch to Sacubitril/Valsartan is avoided)
• Treatment should not be combined w/ ACE inhibitor or ARB or initiated within 36 hours from the last dose
of ACE inhibitor due to a higher risk of angioedema
Beta-Blockers
• Recommended in all stable NYHA Class II-IV patients w/ HFrEF to relieve angina, unless contraindicated or
not tolerated
• Preferred 1st-line treatment to control ventricular rate for patients in NYHA Class I-III provided they are
euvolemic
- May also be used to control the ventricular rate in HF patients w/ preserved EF & AF
• Also used in patients w/ prior MI to reduce mortality, recurrent MI & development of HF
- Slow down symptom onset & decrease cardiac morbidity in post-MI patients w/ asymptomatic LV
dysfunction
• May be considered for ambulatory patients w/ symptomatic HFmrEF to decrease the risk of all-cause & CV death
• Prevent ischemia & inhibit the adverse effects of the sympathetic nervous system in HF
• It is recommended to use only evidence-based beta-blockers (eg Bisoprolol, Carvedilol, Metoprolol succinate)
in patients w/ HFrEF & to initiate treatment in a “start low, go slow” approach
Calcium Channel Blockers
• Dihydropyridine calcium channel blockers are not recommended for HF treatment in patients w/ HFrEF
- May be used to treat hypertension in patients w/ high BP despite optimal GDMT
• Non-dihydropyridine calcium channel blockers that are negative inotropes are contraindicated in patients w/
HFrEF
- However, Diltiazem is sometimes used in patients w/ CHF & AF to decrease excessive exercise-related heart rates
Digoxin
• May be used to slow a rapid ventricular rate in patients w/ symptomatic HF, LVEF ≤40% & AF in addition to
or prior to a beta-blocker
- Recommended as the preferred second drug, in addition to a beta-blocker, to control the ventricular rate in
patients w/ inadequate response to beta-blocker
• May also be used to decrease HF hospitalizations in NYHA Class II-IV patients w/ EF ≤40% in sinus rhythm
& persisting symptoms despite treatment w/ optimized GDMT
Diuretics
• Recommended in NYHA Class II-IV patients w/ HF & those w/ clinical manifestations of congestion or fluid
overload regardless of EF
- Start w/ a low dose & titrate accordingly until clinical improvement is achieved
- Diuretic dosing may need to be reduced w/ increasing doses of ARNI, ACE inhibitor or ARB
- Adjust dose after restoration of dry body weight to avoid risk of dehydration, hypotension & renal dysfunction
• Patients w/ preserved EF are given diuretics to control volume, manage high BP & relieve ischemia
- If after management of volume overload patient w/ preserved EF still has persistent hypertension, ACE
inhibitors or ARBs & beta-blockers should be given to achieve SBP <130 mmHg
• May be considered to reduce the risk of HF hospitalization in patients in sinus rhythm w/ an EF ≤45% who
are unable to tolerate a beta-blocker
• Work synergistically when a different diuretic is used in combination w/ a loop diuretic for the treatment of
resistant edema
• Consider ultrafiltration in patients w/ refractory volume overload not responding to diuretic therapy
Loop Diuretics
• Preferred diuretic for the treatment of HF
• Used in patients w/ more severe volume overload or if there is inadequate response to thiazide
- Produce a greater fractional excretion of filtered sodium & more intense, shorter diuresis
• If high doses of a loop diuretic are reached during treatment (ie equivalent of Furosemide 80 mg 12 hourly),
may consider switching to a different loop diuretic or adding a thiazide diuretic
B139

Diuretics (Cont’d)
• Recommended in patients w/ excessive potassium losses secondary to the use of loop diuretics
• Also used in combination w/ thiazides for the treatment of hypertension
• Caution is needed if a potassium-sparing diuretic is used in addition to ACE inhibitor or ARB & MRA
Thiazide Diuretics
• May be effective as a monotherapy in HF patients w/ mild congestion & normal renal function
Combinations
• Thiazides or Metolazone can be used in combination w/ loop diuretics for a synergistic effect in patients w/
persistent fluid retention despite high-dose loop diuretic treatment
• Chronic daily use of these agents, especially of Metolazone, should be avoided because of the risk of electrolyte
imbalance & dehydration
Hydralazine & Isosorbide Dinitrate
• Given to NYHA Class III-IV black patients w/ HFrEF who remain symptomatic despite optimal standard
therapy w/ ARNI, ACE inhibitor or ARB, beta-blocker, aldosterone antagonist & SGLT2 inhibitor
• Considered an alternative in patients who cannot tolerate ACE inhibitors, ARBs, or ARNI or in whom these
agents are contraindicated & if no other treatment options are available
• Hydralazine & Isosorbide have complementary dilating actions
- Hydralazine may interfere w/ the molecular mechanisms responsible for the progression of HF
- Isosorbide may also inhibit abnormal myocardial & vascular growth thus may reduce ventricular remodeling
Ivabradine
• A highly selective sinus node I(f ) channel inhibitor that is known for slowing the heart rate
• Approved for use in patients w/ ≥75 bpm heart rate
• May be considered to reduce mortality & the risk of HF hospitalization in patients in sinus rhythm w/ an LVEF
≤35%, heart rate of ≥70 bpm at rest, w/ persisting symptoms (NYHA Class II-III) & w/:
- Inadequate response to GDMT including evidence-based dose of beta-blocker
- Intolerance or contraindication to beta-blockers or when there is treatment failure after beta-blocker therapy;
patient should also be given an ACE inhibitor (or ARB/ARNI) & MRA
Mineralocorticoid Receptor Antagonists (MRA)/Aldosterone Antagonists
• Recommended for NYHA Class II-IV patients w/ HFrEF to reduce morbidity & mortality
- Treatment option for patients w/ HFpEF (EF ≥45%, increased BNP, eGFR >30 mL/min/1.73 m2, creatinine
<2.5 mg/dL, potassium <5 mEq/L) to reduce hospitalizations
• Recommended also for NYHA Class II symptomatic patients w/ a history of previous CV hospitalization or
an elevated level of natriuretic peptide
• Spironolactone & Eplerenone block receptors that bind aldosterone & other corticosteroids & are best characterized
as MRAs
• Spironolactone is recommended for patients who remain severely symptomatic despite appropriate doses w/
ACE inhibitors, loop diuretics & Digoxin
- May be considered for ambulatory patients w/ symptomatic HFmrEF without contraindications to decrease
the risk of HF hospitalization & CV death
• Eplerenone is considered in patients w/ systolic HF who still have mild symptoms despite receiving standard
therapy of ACE inhibitors & beta-blockers; has no antiandrogenic effects
• Renal dysfunction & hyperkalemia may lead to underutilization of MRA
- Administration of potassium-lowering agents may allow MRA initiation or uptitration in a large number of
patients w/ hyperkalemia
- Serial monitoring of serum electrolytes & renal enzymes is advised
Nitrates
• A short-acting oral or transcutaneous nitrate is an effective treatment for angina & is safe in patients w/ HF
Rivaroxaban
• May be considered, in addition to Aspirin therapy, for ambulatory patients w/ CAD & CHF in NYHA Class
I/II w/ an LVEF >30% to decrease the risk of stroke & CV death
• Dapagliflozin & Empagliflozin are indicated for patients w/ HFrEF (EF ≤40%) w/ or without diabetes, NYHA
Class II-IV, to decrease the risk of HF hospitalization & death
• A clinical trial showed the benefit of Empagliflozin in the treatment of symptomatic HF patients w/ LVEF >40%
& elevated levels of natriuretic peptides
• Sotagliflozin initiated before or shortly after discharge reduced CV deaths & HF hospitalizations in a clinical trial
• Prior to initiation of therapy, ensure an eGFR of ≥30 mL/min/1.73 m2 for Dapagliflozin & ≥20 mL/min/1.73 m2
for Empagliflozin*
*Reference: 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to
10 pivotal issues about heart failure with reduced ejection fraction. http://www.acc.org.
B140

Tolvaptan
• A vasopressin V2 receptor antagonist that may be used in the short term for the treatment of resistant
hypervolemic hyponatremia despite water restriction & GDMT
- May be given during hospitalization to patients w/ HFrEF who have fluid retention unresponsive to treatment
w/ other diuretics including loop diuretics
• Tolvaptan given during hospitalization for AHF may be used by patients w/ HFpEF after discharge to control
congestion
• Adverse effects may include thirst & dehydration
Vericiguat
• An oral soluble guanylyl cyclase stimulator, Vericiguat may be considered in high-risk patients w/ HFrEF NYHA
Class II-IV w/ worsening HF despite GDMT to decrease the risk of HF hospitalization or CV death
Adjunctive Therapy
Coenzyme Q10 (CoQ10)
• A lipid-soluble cofactor found in the mitochondrial inner membrane that has antioxidant properties & a
bioenergetic role; it is predominantly located in the myocardium
• Q-SYMBIO trial, a double-blind trial on CoQ10 as adjunctive therapy of CHF, found that supplementation w/
CoQ10 was safe & resulted in HF symptom improvement & reduction in major adverse CV events & mortality
• As trials on CoQ10 have shown mixed results, further evidence is needed to establish beneficial effect
Treatment of Comorbidity
Anticoagulation
• Long-term anticoagulation should be given to patients w/ CHF w/ permanent-persistent-paroxysmal AF & a
CHA2DS2-VASc score of ≥2 in men & ≥3 in women
- In eligible patients, direct oral anticoagulant (DOAC) is recommended over Warfarin
- Reasonable therapy for patients w/ CHF w/ permanent-persistent-paroxysmal AF in the absence of additional
risk factors
Intravenous Iron Replacement
• Consider giving in symptomatic patients w/ HFrEF (NYHA Class II & III) & iron deficiency (serum ferritin
<100 ng/mL or 100-300 ng/mL if transferrin saturation is <20%) w/ or without anemia for alleviation of HF
symptoms & improvement of exercise capacity & quality of life
- Also considered in HF patients who are symptomatic & hospitalized recently for HF w/ LVEF <50% & iron
deficiency to decrease the risk of HF hospitalization
Immunization
• Pneumococcal vaccination & annual influenza vaccination, as well as COVID-19 vaccination, are recommended
in all patients w/ HF in the absence of known contraindication
• Pulmonary congestion & pulmonary hypertension increase the risk of respiratory infections (one of the major
causes of acute decompensation, especially in the elderly)
C INTERVENTIONAL THERAPY
Device-based Therapy
Cardiac Resynchronization Therapy (CRT)
• May be performed in patients >40 days post-MI & w/ reasonable expected survival of >1 year
• Recommended if NYHA Class II-IV symptomatic patient is in sinus rhythm w/ a QRS duration of ≥150 msec,
LBBB & LVEF ≤35% despite optimal GDMT for at least 3-6 months; CRT provides high economic value
• Should be considered in NYHA Class II-IV symptomatic HF patient in sinus rhythm w/ LVEF ≤35% & QRS
duration of ≥150 msec & non-LBBB pattern or QRS duration of 120-149 msec & LBBB pattern despite optimal
medical therapy
• CRT w/ a pacemaker is recommended (instead of a right ventricular pacing) in patients w/ HFrEF regardless of
NYHA class or QRS width w/ an indication for ventricular pacing for high-degree AV block, bradycardia, & AF
• Consider an upgrade to CRT in patients w/ LVEF ≤35% who have received a conventional pacemaker or an
ICD & subsequently experience worsening HF despite optimal medical therapy & who have a significant
proportion of right ventricular pacing
• To improve symptoms & quality of life & to reduce hospitalizations & total mortality, CRT may also be
considered in the following patients:
- W/ high-degree or complete heart block & LVEF of 36-50%
- In sinus rhythm NYHA Class III-IV w/ a QRS duration of 120-149 msec, non-LBBB & LVEF ≤35% on GDMT
- W/ ischemic cause of HF, in sinus rhythm NYHA Class I w/ a QRS duration of ≥150 msec, LBBB & LVEF
≤30% on GDMT
- On GDMT w/ LVEF ≤35% & undergoing placement of a new or replacement of a device implant w/ anticipated
requirement for significant ventricular pacing
B141
C INTERVENTIONAL THERAPY (CONT’D)

Device-based Therapy (Cont’d)
Implantable Cardioverter-Defibrillator (ICD)
• Primary prevention or prophylactic ICD implantation to decrease the risk of sudden cardiac death may be
done in a NYHA Class II-III symptomatic patient w/ an LVEF ≤35% or NYHA Class I symptomatic patient w/
an LVEF ≤30% despite optimal GDMT for at least 3-6 months &:
- Without an MI in the prior 40 days
- W/ dilated ischemic cardiomyopathy
- W/ reasonable expected survival of >1 year
• A transvenous ICD is of high economic value in the primary prevention of sudden cardiac death
• ICD may be done for secondary prevention in the following patients to improve survival:
- Cardiac arrest survivors (expected survival rate of >1 year w/ good functional status) from ventricular
fibrillation or w/ hemodynamic instability caused by documented ventricular dysrhythmia
- Those w/ symptomatic CHF & LVEF ≤35% who experience syncope of unclear etiology
- W/ previous MI & LVEF ≤40% w/ non-sustained ventricular tachycardia & ventricular tachycardia or
ventricular fibrillation that is inducible & sustained during an electrophysiological study
• Consider an ICD implantation in patients w/ genetic arrhythmogenic cardiomyopathy w/ high-risk features
of sudden death & EF of ≤45% to decrease sudden death
Left Ventricular Assist Device (LVAD)
• A mechanical circulatory support used as a bridge to transplantation or to recovery
• Should be considered in select NHYA Class IV patients who are deemed dependent on IV inotropes or temporary
mechanical circulatory support
• May be used long-term as a transplantation alternative in patients w/ end-stage HF not eligible for heart
transplantation (destination therapy) or as a bridge to candidacy or heart transplantation
Surgery
Coronary Revascularization
• Eg coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)
• Considered in patients w/ HF w/ LVEF ≤35% & suitable coronary anatomy to relieve persistent angina symptoms
despite optimal GDMT including anti-anginal agents
Valvular Surgery
• Mitral valve repair or replacement may be considered after optimization of GDMT in patients w/ LV systolic
dysfunction & severe mitral regurgitation who will undergo surgical coronary revascularization
- Mitral valve repair may be done in symptomatic patients w/ HF, severe mitral regurgitation & LVEF <30%
- A MitraClip may be considered in select patients w/ HFrEF to decrease mitral regurgitation
- In symptomatic patients w/ chronic moderate-severe to severe mitral regurgitation despite GDMT at
optimal doses, a transcatheter mitral valve edge-to-edge repair may be considered if ineligible for surgery
& not requiring coronary revascularization
- Mitral valve replacement may be considered in symptomatic patients w/ LVEF <30% &/or LV end-systolic
diameter >55 mm unresponsive to medical treatment, w/ comorbidities, & w/ low likelihood for successful
surgical outcome
- Balloon mitral valvuloplasty (BMV) can be considered in patients w/ mitral stenosis w/ suitable valve anatomy
- Percutaneous mitral commissurotomy (PMC) may be considered in symptomatic patients w/ mitral stenosis
w/ valve area >1.5 cm2 w/ suitable valve anatomy at high risk or w/ contraindications for surgery
- Should be considered in asymptomatic patients w/ high thromboembolic risk &/or high risk of hemodynamic
decompensation without contraindications to PMC
• Aortic valve replacement may be considered for patients w/ aortic stenosis or aortic regurgitation
- Recommended for symptomatic patients irrespective of LVEF value
- Should be considered in symptomatic patients w/ LVEF ≤50%, LV enlargement w/ LV end-diastolic diameter
>70 mm, or LV end-systolic diameter >50 mm
- Transcatheter aortic valve replacement (TAVR) or transcatheter aortic valve implantation (TAVI) may be
considered in patients w/ high-risk aortic stenosis or patients not fit for surgery
• Aortic valve repair or valve-sparing surgery should be considered in patients w/ pliable noncalcified tricuspid
or bicuspid valves w/ type I or type II aortic regurgitation
Heart Transplantation
• Considered in eligible patients w/ poor prognosis, advanced or end-stage HF & severe symptoms who have
failed or are refractory to optimal GDMT or device therapy/surgery, & without absolute contraindications
• Significantly increases patient’s survival & quality of life
B142

PROGNOSIS
• Assessment of prognosis provides better information for the patients & their families to plan for their futures
- Validated multivariable risk scores for CHF [eg the Seattle Heart Failure Model, the Heart Failure Survival
score & the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score] have commonly been
used to provide estimates of patient’s survival
• Helps in the identification of patients in whom cardiac transplantation or mechanical device therapy should
be considered
• Patients w/ HF, even w/ stable & well-controlled symptoms, require follow-up at intervals no longer than
6 months to assess symptoms & treatment optimization
- A follow-up visit 1-2 weeks after hospitalization [earlier (within 7 days) if admitted for worsening HF] is
recommended to check for signs of congestion, drug tolerance & to initiate &/or uptitrate evidence-based
therapy
• Patients w/ prior HFrEF who currently have an LVEF of >40% are considered to have an improved LVEF
(HFimpEF) & should continue optimized GDMT, even in those who may become asymptomatic, in order to
avoid LV dysfunction & relapse of HF
• Referral to a HF specialist should be considered in patients needing chronic IV inotropes, w/ NYHA Class
IIIB-IV symptoms or persistently elevated natriuretic peptides, end-organ dysfunction, EF ≤35%, defibrillator
shocks, multiple hospitalizations, edema despite dose escalation of diuretics, low systolic BP/high heart rate,
& progressive intolerance or down-titration of GDMT
- Other indications for referral of advanced HF include a new-onset HF regardless of EF, CHF w/ high-risk
features, HF etiology requiring a second opinion, yearly review of patients w/ confirmed advanced HF &
patient assessment for possible clinical trial inclusion
• Provide palliative & end-of-life care services to patients w/ advanced HF
Conditions Associated w/ a Poor Prognosis in Heart Failure
• Advanced age
• Ischemic etiology
• Worsening NYHA functional status (Class III-IV)
• Chronic hypotension
• Resting tachycardia
• Intolerance to GDMT at optimal dose
• Increasing need for diuretics, refractory volume overload
• >1 HF hospitalization within the last year
• Resuscitated sudden death, CRT non-responder clinically
• Decreasing peak exercise O2 uptake
• Iron deficiency w/ or without anemia
- Anemia is independently associated w/ the severity of HF & iron deficiency seems to be uniquely associated
w/ a reduction in exercise capacity
- Iron deficiency in HF patients is associated w/ a worse prognosis
• Progressive deterioration of hepatic or renal function
• Persistent hyponatremia
• Marked elevation of BNP/NT-proBNP
• Elevated biomarkers of myocardial fibrosis (soluble ST2 receptor, galectin-3, high sensitivity cardiac troponin)
& neurohormonal activation
• Widened QRS >120 msec on 12-lead ECG
• Tachycardia & Q waves
• LVH & complex ventricular arrhythmias
• Decreasing LVEF
B143
Dosage Guidelines
ACE INHIBITORS
Drug Dosage Remarks

Adjust dose gradually • CV effects (hypotension, palpitations); CNS effects
according to response (fatigue, headache, dizziness); GI effect (taste
Max dose: 20 mg/day disturbances); Resp effects (persistent dry cough, upper
resp tract symptoms); Dermatologic effects (skin rashes,
Captopril Initial dose: 6.25-12.5 mg PO erythema multiforme, toxic epidermal necrolysis,
8-12 hrly pruritus, angioedema, photosensitivity reaction); Renal
Adjust dose gradually effect (renal impairment); Other effects (electrolyte
according to response disturbances, eg hyperkalemia, hyponatremia; blood
Maintenance dose: 25 mg PO disorders)
8-12 hrly or 50 mg PO 8 hrly Special Instructions
Max dose: 150 mg/day • Patients w/ HF & those who may be salt or water
Cilazapril Initial dose: 0.5 mg PO 24 hrly depleted (taking diuretic or on dialysis) may experience
Maintenance dose: 1-2.5 mg hypotension during initial stages of ACE inhibitor
PO 24 hrly therapy
Max dose: 5 mg PO 24 hrly - Start treatment only under close medical supervision;
in these patients use a low dose & have the patient in a
Enalapril Initial dose: 2.5 mg PO 24 hrly supine position
Maintenance dose: 20 mg PO • Start w/ low dose & if lower doses have been tolerated,
24 hrly or divided 12 hrly gradually increase dose every 2 wk until maximum
Max dose: 40 mg/day tolerated dose is achieved
Fosinopril Initial dose: 10 mg PO 24 hrly • Avoid in patients w/ aortic stenosis, mitral stenosis,
outflow tract obstruction, renovascular disease (eg renal
Adjust dose gradually
artery stenosis, severe renal insufficiency) & hereditary
according to response
or idiopathic angioedema
Max dose: 40 mg/day
• Should not be given to patients if they have experienced
Imidapril Initial dose: 2.5-10 mg PO life-threatening adverse reactions (angioedema or renal
24 hrly failure) w/ or without previous exposure to the drug,
Adjust dose gradually hypotensive patients who are at immediate risk of
according to patient’s age & cardiogenic shock
response • Check BP, renal function & electrolytes 1-2 wk after each
dose increment, at 3 mth then every 6 mth
- More frequent monitoring is necessary in patients w/
• NSAIDs should be avoided since they can block the
beneficial effects & increase adverse effects of ACE
inhibitors & may synergistically compromise renal
function

B144

Dosage Guidelines
ACE INHIBITORS (CONT’D)

Drug Dosage Remarks
Lisinopril Initial dose: 2.5 mg PO 24 hrly Adverse Reactions
Maintenance dose: 5-20 mg PO • CV effects (hypotension, palpitations); CNS effects
24 hrly (fatigue, headache, dizziness); GI effect (taste
Max dose: 40 mg/day disturbances); Resp effects (persistent dry cough,
upper resp tract symptoms); Dermatologic effects
Perindopril1 Initial dose: 2-2.5 mg PO 24 hrly (skin rashes, erythema multiforme, toxic epidermal
Maintenance dose: 4-5 mg PO necrolysis, pruritus, angioedema, photosensitivity
24 hrly reaction); Renal effect (renal impairment); Other
Quinapril Initial dose: 5 mg PO 12-24 hrly effects (electrolyte disturbances, eg hyperkalemia,
Maintenance dose: 10-40 mg/ hyponatremia; blood disorders)
day PO divided 12 hrly Special Instructions
Max dose: 40 mg/day • Patients w/ HF & those who may be salt or water
depleted (taking diuretic or on dialysis) may
Ramipril Initial dose: 1.25 mg PO 24 hrly experience hypotension during initial stages of ACE
Adjust dose gradually according inhibitor therapy
to response - Start treatment only under close medical
Doses ≥2.5 mg/day may be given supervision; in these patients use a low dose & have
24 hrly or divided 12 hrly the patient in a supine position
Max dose: 10 mg/day • Start w/ low dose & if lower doses have been tolerated,
Trandolapril Initial dose: 1 mg PO 24 hrly gradually increase dose every 2 wk until maximum
tolerated dose is achieved
to response • Avoid in patients w/ aortic stenosis, mitral stenosis,
outflow tract obstruction, renovascular disease (eg
Max dose: 4 mg/day
renal artery stenosis, severe renal insufficiency) &
hereditary or idiopathic angioedema
• Should not be given to patients if they have
experienced life-threatening adverse reactions
(angioedema or renal failure) w/ or without previous
exposure to the drug, hypotensive patients who are at
immediate risk of cardiogenic shock
• Check BP, renal function & electrolytes 1-2 wk after
each dose increment, at 3 mth then every 6 mth
- More frequent monitoring is necessary in patients
w/ previous or existing renal dysfunction
• NSAIDs should be avoided since they can block the
beneficial effects & increase adverse effects of ACE
inhibitors & may synergistically compromise renal
function
1Combination w/ Bisoprolol is available.

B145
Dosage Guidelines
ADRENERGIC AGONIST
Drug Dosage Remarks
Dopamine Initial dose: Adverse Reactions
2-5 mcg/kg/min IV infusion • CV effects (ectopic beats, tachycardia, palpitations,
Gradually increase by anginal pain, hypotension, vasoconstriction); Other
5-10 mcg/kg/min effects (N/V, headache, dyspnea)
Max dose: 20-50 mcg/kg/min • Less common: CV effects (bradycardia, cardiac
conduction abnormalities, hypertension may occur if
overdosage); Other effects (piloerection, azotemia)
• Hypovolemia should be corrected prior to treatment
• Avoid in patients w/ pheochromocytoma,
hyperthyroidism & uncorrected tachyarrhythmias or
ventricular fibrillation
• Use w/ caution & in low dose in patients w/ shock
secondary to MI, patients w/ history of peripheral
vascular disease (PVD) who are at increased risk of
ischemia of the extremities
• Use w/ caution in patients w/ hypersensitivity to
sodium metabisulfite
• When discontinuing, it may be necessary to gradually
decrease the dose while expanding blood volume w/ IV
fluids to prevent hypotension
Drug Dosage Remarks
Candesartan Initial dose: 4 mg PO 24 hrly Adverse Reactions

Increase dose at intervals of • Usually mild & transient: CNS effects (dizziness,
2 wk to reach the target dose headache); CV effect (dose-related orthostatic
Max dose: 32 mg/day hypotension which may occur particularly in patients w/
volume depletion)
Losartan Initial dose: 12.5 mg PO 24 hrly Special Instructions
Titrated at wkly intervals to • Patients w/ volume depletion (eg high-dose diuretic
12.5 mg, 25 mg, 50 mg, therapy) may experience hypotension & should be
100 mg PO 24 hrly up to started on low dose
Max dose: 150 mg/day • Use w/ caution in patients w/ renal artery stenosis, renal
Valsartan Initial dose: 40 mg PO 12 hrly impairment or hepatic impairment, aortic stenosis,
May increase to 80-160 mg mitral stenosis, obstructive hypertrophic
PO 12 hrly at least at 2-wk cardiomyopathy, primary hyperaldosteronism
interval • Contraindicated in patients w/ severe renal or hepatic
Max dose: 320 mg/day dysfunction & cholestasis
• Check BP, renal function & electrolytes 1-2 wk after
each dose increment, at 3 mth then every 6 mth
- More frequent monitoring is necessary in patients w/

B146

Dosage Guidelines
ANGIOTENSIN II ANTAGONISTS (CONT’D)

Drug Dosage Remarks
Sacubitril/ 100 mg PO 12 hrly doubled Adverse Reactions
Valsartan up to 200 mg PO 12 hrly • GI effects (diarrhea, nausea, gastritis); CNS effects (dizziness,
after 2-4 wk headache, syncope, asthenia); Metabolic effects (hyper- or
Patient not on ACE hypokalemia, hypoglycemia); Other effects (hypotension, renal
inhibitor or ARB impairment, anemia, cough, fatigue)
Starting dose: 50 mg PO Special Instructions
12 hrly • Administer until 36 hr after last dose of ACE inhibitor
• Temporary down-titration/discontinue administration in case
of symptomatic hypotension, hyperkalemia or renal
dysfunction
• Treatment should not be initiated in patient w/ serum K level
>5.4 mmol/L or SBP <100 mmHg; not recommended for
end-stage renal disease
• Starting dose of 50 mg 12 hrly is recommended for patient w/
eGFR <30 mL/min/1.73 m2 (use w/ caution) or moderate
hepatic impairment (Child-Pugh Class B) or if patient is taking
Enalapril ≤10 mg/day or equivalent or Valsartan ≤160 mg/day
or equivalent
• Starting dose of 100 mg 12 hrly is recommended for patient
taking Enalapril >10 mg/day or equivalent or Valsartan >160
mg/day or equivalent
• Caution is required in patient w/ renal artery stenosis &
monitoring of renal function is recommended; caution when
initiating in patient w/ NYHA Class IV
• Contraindicated in patients w/ known history of angioedema
related to previous ACE inhibitor or ARB therapy, hereditary
or idiopathic angioedema, concomitant use w/ ACE inhibitors
or ARBs, Aliskiren-containing medicinal products in patients
w/ DM or renal impairment, severe hepatic impairment, biliary
cirrhosis & cholestasis
• Check BP, renal function & electrolytes after initiation &
during dose titration

B147
Dosage Guidelines
ANTI-ANGINAL DRUG
Drug Dosage Remarks
Ivabradine1 Initial dose: Adverse Reactions
<75 yr: 5 mg PO 12 hrly • Ophtha effects [luminous phenomena (phosphenes), blurred
≥75 yr: 2.5 mg PO 12 hrly vision]; CV effects (bradycardia, AV block, ventricular
Titrate dose after 2 wk extrasystoles, palpitation); CNS effects (headache, dizziness,
depending on patient’s syncope)
heart rate: Special Instructions
>60 bpm: Increase by • Should be taken w/ food; avoid excessive consumption of
2.5 mg PO 12 hrly until grapefruit juice
max dose of 7.5 mg PO • Use w/ caution in patients w/ hypotension, arrhythmias,
12 hrly moderate hepatic impairment, congenital QT syndrome &
50-60 bpm: Maintain patients taking QT-prolonging drugs, severe renal impairment
current dose • Contraindicated in patients w/ resting heart rate <70 bpm
<50 bpm: Decrease by prior to treatment, BP <90/50 mmHg, sick sinus syndrome, SA
2.5 mg PO 12 hrly or block, unstable or AHF, pacemaker dependent, unstable
discontinue if already at angina, 3rd degree AV block, cardiogenic shock, acute MI,
2.5 mg PO 12 hrly severe hepatic impairment
Max dose: 7.5 mg PO • Monitor heart rate, BP & cardiac rhythm
12 hrly • Discontinue if symptoms of bradycardia persist even after dose
titration
1Combination w/ Carvedilol is available.

B148

Dosage Guidelines
ANTIDIABETIC AGENTS
Drug Dosage Remarks
Dapagliflozin 10 mg PO 24 hrly Adverse Reactions
Empagliflozin 10 mg PO 24 hrly • GU effects (polyuria, dysuria, vulvovaginitis, balanitis,
increased susceptibility to infections); Renal effect (acute
kidney injury); Hematologic effect (increased hematocrit); GI
effects (nausea, constipation); CV effects (hypotension,
decreased blood volume); Other effects (dyslipidemia,
increased creatinine & urea levels, hypoglycemia, rash,
hyperhidrosis, back pain, euglycemic diabetic ketoacidosis)
• Electrolyte disturbances (hyperphosphatemia,
hypermagnesemia, hyperkalemia)
• Monitor kidney function prior to starting therapy & assess
periodically during therapy
• Should not be given in patients w/ severe renal impairment
• Though current evidence suggests that CV & renal benefits
appear to be maintained even at eGFR levels as low as 30 mL/
min/1.73 m², physicians need to recognize that at a level of
CKD stage 3b & lower, the glucose-lowering efficacy of SGLT2
inhibitors is weak
• Use w/ caution in patients taking diuretics, NSAIDs & those w/
decreased blood volume & congestive heart failure
• May need to lower doses of insulin, sulfonylurea, insulin
secretagogues when used concomitantly w/ SGLT2 inhibitors
• Consider withholding SGLT2 inhibitors in events that may
precipitate diabetic ketoacidosis, eg intercurrent illness,
surgery (elective or emergency), trauma, severe carbohydrate
restriction
• SGLT2 inhibitors are generally safe for diabetic patients during
Ramadan but should be discontinued in select patients whose
risk for adverse effects might be increased

B149
Dosage Guidelines
BETA-BLOCKERS
Drug Dosage Remarks
Bisoprolol1 Initial dose: 1.25 mg PO 24 hrly x Adverse Reactions
1 wk • CNS effects (fatigue, depression, dizziness,
If tolerated, increase to 2.5 mg PO headache, confusion, sleep disturbances); CV
24 hrly x 1 wk effects (HF, heart block, coldness of extremities,
If tolerated, increase to 3.75 mg PO male impotence); Resp effects (bronchospasm in
24 hrly x 1 wk susceptible patients & drugs w/ beta1 selectivity
If tolerated, increase to 5 mg PO should be used w/ caution in these patients); GI
24 hrly x 4 wk effects (N/V, constipation, diarrhea); Metabolic
effects (can produce hyper- or hypoglycemia,
If tolerated, increase to 7.5 mg PO changes in serum cholesterol & triglycerides)
24 hrly x 4 wk
If tolerated, increase to:
• Patients should be on optimal therapy w/ ACE
Max dose: 10 mg PO 24 hrly inhibitors (unless contraindicated) & should be in
Carvedilol2 Initial dose: 3.125 mg PO 12 hrly x stable condition without need of IV inotropic
2 wk therapy & without signs of marked fluid retention
If tolerated, increase to 6.25 mg PO • Dose should be titrated individually every 2 wk to
12 hrly x 2 wk maximum dose tolerated by the patient
If tolerated, increase to 12.5 mg PO • During the titration period (increase or decrease
12 hrly x 2 wk in dose), monitor patient for HF symptoms, fluid
retention, hypotension, bradycardia & adjust
If tolerated, increase to 25 mg PO ACE inhibitors, diuretics & other drugs as
12 hrly necessary
Max dose in patients <85 kg: 25 mg • Patients need to be aware that clinical response
PO 12 hrly to beta-blockers may take 2-3 mth
Max dose in patients ≥85 kg: 50 mg - If improvement in symptoms does not occur,
PO 12 hrly beta-blockers should still be continued to
or reduce risk of major clinical events
10 mg PO 24 hrly x 2 wk • Contraindicated in severe bradycardia, 2nd- or
Increase dosage to 20 mg, 40 mg, & 3rd-degree AV block, SA block, sick sinus
then 80 mg PO 24 hrly over intervals syndrome & severe, unstable LV failure or acute
of at least 2 wk as tolerated HF, hypotension, cardiogenic shock, severe
asthma, late stages of peripheral arterial occlusive
Metoprolol 12.5-25 mg PO 24 hrly disease & Raynaud’s syndrome, untreated
If tolerated, may titrate dose up to: pheochromocytoma, metabolic acidosis
Max dose: 200 mg PO 24 hrly • Use w/ caution in patients w/ bronchospasm,
asthma or obstructive airway diseases, 1st-degree
Nebivolol Initial dose: 1.25 mg PO 24 hrly AV block, Prinzmetal’s angina, depression,
May increase dose stepwise at patients w/ PVD, renal or hepatic dysfunction,
1-2 wkly intervals, depending on thyrotoxicosis, psoriasis & patients on Insulin
patient tolerability to 2.5 mg PO, • Beta-blockers may mask the symptoms of
5 mg PO & 10 mg PO 24 hrly hyperthyroidism & hypoglycemia & may
Max dose: 10 mg PO 24 hrly aggravate psoriasis
• Patients on long-term treatment should not
discontinue abruptly; should discontinue
gradually over 1-2 wk
2Combination w/ Ivabradine is available.

B150

Dosage Guidelines
CALCIUM ANTAGONISTS
Drug Dosage Remarks
Dihydropyridines Adverse Reactions
Amlodipine Initial dose: 5 mg PO 24 hrly • CV effects (depression of cardiac function, hypotension,
worsening HF, edema, flushing, tachycardia, palpitations,
Max dose: 10 mg/day
ischemic chest pain); GI effects (nausea, dyspepsia, dry
Benidipine Initial dose: 2-4 mg PO 24 hrly mouth, constipation, abdominal pain, abnormal LFTs,
Max dose: 8 mg/day gingival hyperplasia); CNS effects (headache, dizziness,
tremor, insomnia, paresthesia); Hematologic effect
Felodipine Initial dose: 5 mg PO 24 hrly (thrombocytopenia); Dermatologic effect (rashes)
Max dose: 10 mg/day • Short-acting dihydropyridine agents should be avoided
Isradipine Initial dose: 1.25 mg PO because they have the potential to enhance risk of
12 hrly or 2.5 mg PO 24 hrly adverse cardiac events
Nicardipine Initial dose: 20 mg PO 8 hrly
• Contraindicated in patients w/ overt decompensated HF,
May increase at intervals of at though vasoselective dihydropyridines (eg Amlodipine,
least 3 days until required effect Felodipine) are tolerated in patients w/ a decreased LVEF
is achieved
• Avoid in patients w/ cardiogenic shock, recent MI or
Maintenance dose: 30 mg PO acute unstable angina, severe aortic stenosis
8 hrly or 60-120 mg in divided
doses • Use w/ caution in patients w/ acute cerebral infarction
or hemorrhage, pheochromocytoma, hepatic
Nisoldipine Initial dose: 10 mg PO 24 hrly impairment or decreased hepatic blood flow, portal
Maintenance dose: hypertension, renal impairment & CHF
20-40 mg PO 24 hrly • Sudden withdrawal may exacerbate angina
CARDIAC GLYCOSIDES
Drug Dosage Remarks
Digoxin 62.5-250 mcg Adverse Reactions
PO 24 hrly • Side effects usually due to Digoxin toxicity or overdosage & Digoxin is
Elderly, usually well-tolerated at the recommended doses for CHF
patients w/ • Digoxin toxicity: GI effects (N/V, anorexia, diarrhea, abdominal pain)
impaired renal are usually the 1st signs of Digoxin toxicity; Other signs of toxicity: CNS
function or effects (headache, fatigue, facial pain, weakness, dizziness, mental
low lean body confusion); Visual disturbances (blurred vision, color disturbances);
mass: 62.5 mcg/ Toxic doses may cause serious CV effects (aggravation of HF,
day PO or arrhythmias, conduction disturbances)
125 mcg PO • Hypokalemia can predispose a person to Digoxin toxicity
every other day Special Instructions
Metildigoxin 100-600 mcg • Loading doses are not necessary in CHF patients
(Methyl PO 24 hrly • Avoid in patients w/ obstructive cardiomyopathy unless there is severe
digoxin) HF, in patients w/ Wolff-Parkinson-White (WPW) syndrome or
evidence of accessory pathway
• Contraindicated in patients w/ ventricular tachycardia, intermittent
complete heart block or 2nd-degree AV block
• Use w/ caution in partial heart block, sinus node disorders, acute
myocarditis, acute MI, advanced HF, severe pulmonary disease, thyroid
dysfunction, in patients undergoing electrocardioversion (withhold
Digoxin for 24 hr prior to procedure) & w/ other drugs that can depress
the sinus or AV nodal function (eg Amiodarone or beta-blocker)
• Hypokalemia, hypercalcemia, hypomagnesemia, hypoxia &
hypothyroidism may affect the sensitivity to Digoxin
• Monitoring of Digoxin levels is only necessary if there is suspected toxicity

B151
Dosage Guidelines
DIURETICS
Drug Dosage Remarks
Eplerenone Initial dose: 25 mg PO Adverse Reactions
24 hrly • CNS effects (headache, dizziness, drowsiness, ataxia,
May increase dose to mental confusion); GI effects (cramps, diarrhea, abdominal
50 mg PO 24 hrly pain, elevated liver enzymes); CV effect (angina); Endocrine
within 4 wk & metabolic effects (gynecomastia, hirsutism, menstrual
Max dose: 50 mg/day irregularities, impotence, mild acidosis, hyponatremia,
hyperkalemia, increased uric acid, & transient increases in
Spironolactone1 Initial dose: BUN); Resp effect (cough); Dermatologic effects (rash,
12.5-25 mg PO 24 hrly angioneurotic edema)
If after 1 mth patient is Special Instructions
still symptomatic but
normokalemic, increase • Prior to initiation of therapy, verify that eGFR ≥30 mL/
dose to 50 mg PO min/1.73 m2, creatinine ≤2.5 mg/dL (men) or ≤2 mg/dL
24 hrly (women) & serum K ≤5 mEq/L
• Closely monitor serum K & renal function 3 days after
initiating therapy, at 1 wk after initiation, at least mthly for
the 1st 3 mth of treatment, then every 3 mth thereafter
• Avoid in patients w/ hyperkalemia, severe renal
impairment or Addison’s disease
• Use w/ caution in patients at increased risk of developing
hyperkalemia (eg DM, elderly, patients w/ renal or hepatic
impairment)
Carbonic Anhydrase Inhibitor
Acetazolamide 250-375 mg PO 24 hrly Adverse Reactions
in the morning • CNS effects (paresthesia, drowsiness, confusion); Other
effects (loss of appetite, hearing dysfunction, taste
alteration, GI disturbances, polyuria, acidosis, transient
myopia)
• Avoid in patients w/ depressed Na &/or K blood serum
levels, marked kidney or liver disease, hyperchloremic
acidosis, cirrhosis
• Use w/ caution in patients w/ pulmonary obstruction or
emphysema; rapid ascent to high altitude
1Combinations of Spironolactone & Hydroflumethiazide; Spironolactone & Furosemide are available.

B152

Dosage Guidelines
Drug Dosage Remarks
Loop Diuretics
Bumetanide Initial dose: 0.5-1 mg Adverse Reactions
PO 24 hrly • Endocrine & metabolic effects (hypomagnesemia, hyponatremia,
Give 2nd dose 6-8 hr hypokalemia & hypochloremic alkalosis especially after large
later if necessary doses or prolonged administration, hyperglycemia, glycosuria,
High doses may be hyperuricemia & may precipitate gout)
given 8-12 hrly • Signs of electrolyte imbalance: Headache, hypotension,
Max dose: 10 mg/day muscle cramps, dry mouth, drowsiness, thirst, weakness
Furosemide Initial dose: 20-80 mg • Avoid in patients w/ anuria or in renal insufficiency caused by
(Frusemide)1 PO 12-24 hrly nephrotoxic or hepatotoxic drugs or caused by hepatic coma
Max dose: 600 mg/day • Contraindicated in patients w/ severe electrolyte depletion,
Torasemide 10-20 mg PO 24 hrly hypersensitivity to sulfonamides & Furosemide, Addison’s disease
(Torsemide) Max dose: 200 mg/day • Use w/ caution in patients w/ existing or at a risk of fluid &
electrolyte imbalances, prostatic hyperplasia, impairment of
micturition & gout
• Patients w/ hepatic cirrhosis are more likely to develop
hypokalemia & patients w/ severe HF are more likely to suffer
hyponatremia
• Monitor patient’s BP, renal function & electrolytes after
initiation & during dose titration
Amiloride2 Patient on ACE Adverse Reactions
inhibitor • Endocrine & metabolic effects (hyperkalemia especially in the
Initial dose: elderly, patients w/ DM & patients w/ impaired renal function,
2.5 mg PO 24 hrly hyponatremia has occurred in patients receiving combination
Max dose: 20 mg/day diuretic therapy); GI effects (N/V, abdominal pain, diarrhea,
Patient not on ACE constipation, thirst); CNS effects (headache, dizziness, weakness,
inhibitor paresthesia); CV effect (orthostatic hypotension); Dermatologic
effects (rash, pruritus)
Initial dose: 5-10 mg
PO 24 hrly Special Instructions
Max dose: 20 mg/day • Use only if hypokalemia persists after the start of ACE
inhibitors & other diuretics
Triamterene Patient on ACE • Avoid in patients w/ hyperkalemia or severe renal impairment
inhibitor • Use w/ caution in patients at increased risk of developing
Initial dose: hyperkalemia (eg DM, elderly, patients w/ renal or hepatic
25 mg PO 24 hrly impairment)
Max dose: 100 mg/day • Use 1 wk low dose & check serum K & creatinine after
Patient not on ACE 5-7 days of therapy & titrate dose as required
inhibitor - Continue to recheck serum K & creatinine every 5-7 days
Initial dose: until K values are stable
100 mg PO 12 hrly - Monitor serum electrolytes regularly
Max dose: 300 mg/day • Discontinue for at least 3 days before glucose tolerance tests
are done
1Combination w/ Spironolactone is available.
2Combination w/ Hydrochlorothiazide is available..

B153
Dosage Guidelines
Drug Dosage Remarks
Thiazides & Related Diuretics
Bendroflumethiazide Initial dose: 5-10 mg PO Adverse Reactions
24 hrly or on alternate days • CV effects (postural hypotension, venous
Maintenance dose: thrombosis); Endocrine & metabolic effects
2.5-10 mg PO 1-3x/wk (hyperuricemia & may precipitate gout in some
Max dose: 20 mg/day patients, hypochloremic alkalosis,
hyponatremia, hypokalemia, hyponatremia,
Chlortalidone Initial dose: 25-50 mg PO hypomagnesemia, hyperglycemia & glucosuria
(Chlorthalidone) 24 hrly in DM or other susceptible patients, altered
May increase to 100-200 mg lipid concentrations); GI effects (GI irritation,
PO 24 hrly in severe cases N/V, constipation, anorexia, diarrhea,
Maintenance dose: pancreatitis, intrahepatic cholestasis); CNS
25-50 mg PO 24 hrly or on effects (headache, dizziness, lethargy, syncope,
alternate days vertigo, paresthesia); Dermatologic effects
Max dose: 200 mg/day (hypersensitivity reactions, photosensitivity);
GU effect (impotence)
Cyclopenthiazide Initial dose: 0.25-0.5 mg PO
24 hrly • Signs of electrolyte imbalances: Headache,
muscle cramps, dry mouth, hypotension, thirst,
Reduce to lowest effective weakness, drowsiness
dose for maintenance
Max dose:
1 mg PO 24 hrly • Do not use thiazides if GFR <30 mL/min unless
used synergistically w/ loop diuretics
Hydrochlorothiazide1 Initial dose: 25 mg PO • Avoid in patients w/ severe hepatic impairment
(Dihydrochlorothiazide) 24 hrly if encephalopathy may be precipitated, in
Maintenance dose: patients w/ severe renal impairment or anuria,
25-100 mg PO 24 hrly in patients w/ preexisting hypercalcemia,
Max dose: 200 mg/day symptomatic hyperuricemia, sulfonamide
allergy, Addison’s disease & refractory
Indapamide Initial dose: 2.5 mg PO
hypokalemia, hyponatremia
24 hrly
• Use w/ caution in patients w/ existing or at risk
May increase to 5 mg PO
of fluid & electrolyte imbalances (eg elderly),
24 hrly after 1 wk if
patients w/ hepatic cirrhosis are more likely to
necessary
develop hypokalemia & patients w/ severe HF
Max dose: 5 mg/day are more likely to suffer hyponatremia
Metolazone Initial dose: 2.5 mg PO • Use w/ caution in patients w/ hepatic & renal
24 hrly impairment, porphyria, hyperlipidemia &
May increase to 20 mg PO extrasystole
24 hrly • May exacerbate SLE & aggravate DM & gout
Max dose: 80 mg/day • Monitor patient for signs of fluid & electrolyte
imbalance
1Combination w/ Amiloride or Candesartan is available.

B154

Dosage Guidelines
Drug Dosage Remarks
Vasopressin Antagonist
Tolvaptan Usual dose: Adverse Reactions
15 mg PO 24 hrly • GI effects (dry mouth, constipation); Endocrine effects (thirst,
May increase to polyuria, hyperglycemia)
30 mg PO 24 hrly after Special Instructions
at least 24 hr • Assess serum Na concentration & neurologic status especially
For patients w/ serum during initiation & after titration
Na <125 mEq/L or for • Carefully monitor patient’s fluid intake, urine volume, serum Na
whom rapid volume level & for occurrence of clinical symptoms (eg thirst, dehydration)
decrease is considered • Contraindicated in cases of urgent need to raise serum Na acutely,
inappropriate: in hypernatremia, in patients unable to autoregulate fluid balance
Start w/ 7.5 mg PO • Discontinue treatment if serum Na is increased above normal
24 hrly range, if significant signs & symptoms of dehydration &
Max dose: 60 mg/day hypovolemia are present
Max duration of • Use w/ caution in hyperkalemia or drugs that increase serum K,
therapy: 30 days co-administration w/ hypertonic saline solutions
NITRATES (ORAL)
Available
Drug Dosage Remarks
Strength
Glyceryl 400, 500, 400-600 mcg SL every 5 min Adverse Reactions
trinitrate 600 mcg until cessation of pain or side • CNS effects (headache,
(Nitroglycerin, sublingual (SL) effects occur lightheadedness, dizziness,
GTN, NTG) tab Max dose: 3 doses within 15 min syncope, vertigo, restlessness,
confusion); rarely CV effects
400 mcg/dose 1-2 sprays (400-800 mcg) SL,
(tachycardia, hypotension, flushing,
SL spray closing the mouth after spraying
palpitation); GI effects (N/V, bowel
Max dose: 3 doses within 15 min incontinence, xerostomia)
Isosorbide 5 mg, 10 mg SL 5-10 mg SL every 2-3 hr until Special Instructions
dinitrate tab cessation of pain or side effects • Nitrate-free interval is
occur recommended in patients on
or long-term therapy w/ nitrates to
30-160 mg PO daily in divided decrease the risk of nitrate tolerance
doses • Avoid in patients w/ severe
Max dose: 240 mg/day PO hypotension, hypovolemia, marked
anemia, HF due to obstruction or
20 mg retard tab 20 mg PO 12 hrly raised intracranial pressure due to
1.25 mg/dose 1-3 sprays (1.25-3.75 mg) into head trauma or hemorrhage
buccal spray the buccal cavity, waiting 30 sec • Use w/ caution in patients w/
between sprays severe renal or hepatic
Do not inhale medication dysfunction, hypothyroidism,
malnutrition, mitral valve
Isosorbide 20 mg/tab 20 mg PO 12 hrly prolapse, arterial, hypoxemia,
5-mononitrate Max dose: 120 mg/day glaucoma or hypothermia
(Isosorbide
mononitrate) 50 mg/cap 50 mg PO 24 hrly • Co-administration w/
May increase to 100 mg PO phosphodiesterase inhibitors (eg
simultaneously Sildenafil) is contraindicated
within 24-hr interval after taking
60 mg/tab 30-60 mg PO 24 hrly a nitrate preparation

B155
Dosage Guidelines
VASODILATORS USED IN CARDIAC DISEASES1

Drug Dosage Remarks
Hydralazine In combination w/ Adverse Reactions
Isosorbide dinitrate: • Typically subside w/ continued therapy: CV effects
Initial dose: 25 mg (tachycardia, palpitations, angina, flushing); GI effects
PO 6-8 hrly (anorexia, N/V, diarrhea); Other effects (dizziness, nasal
May increase every congestion)
2 days if needed • Other CV effects (postural hypotension, fluid retention,
Maintenance dose: edema); Other effects (wt gain, tremor, conjunctivitis, muscle
50-75 mg PO 6 hrly cramps, lacrimation)
• Avoid in patients w/ severe tachycardia, HF w/ high cardiac
output, dissecting aortic aneurysm, cor pulmonale or
myocardial insufficiency due to mechanical obstruction
(eg aortic stenosis, mitral stenosis, constrictive pericarditis),
idiopathic SLE & related disorders
• Use w/ caution in patients w/ ischemic heart disease, recent
MI, cerebrovascular disorders, impaired renal or hepatic
function
• CBC, antinuclear antibody determinations & urinalysis should
be done periodically during long-term therapy
• Monitor BP & heart rate after initiation & during dose titration
Isosorbide Use in combination Adverse Reactions
dinitrate w/ Hydralazine • CNS effects (headache which usually decreases w/ long-term
Initial dose: 20 mg administration, lightheadedness, dizziness, syncope, confusion,
PO 8 hrly x 2-4 wk weakness, restlessness, vertigo); rarely CV effects (palpitations,
If tolerated, increase tachycardia, hypotension, flushing); GI effects (N/V, abdominal
dose to pain, bowel incontinence, xerostomia)
Maintenance dose: • Nitrate tolerance usually develops w/ long-term use & dosing
40 mg PO 8 hrly w/ adequate nitrate-free interval is recommended
Max dose: 120 mg/day Special Instructions
• Avoid in patients w/ severe hypotension, hypovolemia, marked
anemia, HF due to obstruction or raised intracranial pressure
due to head trauma or hemorrhage
• Use w/ caution in patients w/ severe renal or hepatic
dysfunction, hypothyroidism, malnutrition or hypothermia
• Co-administration w/ phosphodiesterase inhibitors
(eg Sildenafil) are contraindicated
• Monitor BP & heart rate after initiation & during dose titration
1 Thecombination of Hydralazine & Isosorbide dinitrate should not be used for the treatment of HF in patients who have no prior use
of ACE inhibitor & should not be substituted for ACE inhibitor in patients who are tolerating ACE inhibitors without difficulty.

B156

Dosage Guidelines
OTHER CARDIOVASCULAR DRUGS

Drug Dosage Remarks
Levosimendan Individualize dosage Adverse Reactions
Initial dose: • Hematologic effect (decreased Hb): Metabolic effect
6-24 mcg/kg IV over (hypokalemia); CNS effects (dizziness, headache);
10 min followed by CV effects (hypotension, myocardial ischemia,
Continuous infusion: extrasystoles, AF, tachycardia, ventricular tachycardia);
0.1 mcg/kg/min for GI effects (N/V)
24 hr Special Instructions
If tolerated & an • Contraindicated in patients w/ severe renal or hepatic
increased hemodynamic impairment, significant mechanical obstructions affecting
effect is required, may ventricular filling or outflow or both, severe hypotension &
increase to 0.2 mcg/kg/ tachycardia, history of torsades de pointes
min • Use w/ caution in patients w/ mild to moderate renal or
Rate of infusion may hepatic impairment, ischemic CV disease & concurrent
be decreased to anemia, tachycardia or AF w/ rapid ventricular response,
0.05 mcg/kg/min or ongoing coronary ischemia, acute HF related to a recent
discontinued if the onset of a non-cardiac condition, serious deterioration of
response is deemed HF after surgery & severe HF awaiting heart
excessive transplantation; concomitant use w/ other inotropic agents
(except Digoxin) or QTc-prolonging drugs
• Monitor serum K levels, changes in BP or heart rate
Ubidecarenone Adjunctive therapy: Adverse Reactions
(Coenzyme Q10, 30-200 mg PO 24 hrly • GI effects (nausea, epigastric pain, heartburn, diarrhea);
Ubiquinone-10) Other effects (appetite suppression, rash, sleep
disturbances)
• Monitor INR if taken concomitantly w/ Warfarin

B157
Hypertension (1 of 30)
1
Adult patient presents w/ elevated
blood pressure (BP)
2
No Yes
DIAGNOSIS
Mean BP readings Patient is
are normal Is hypertension hypertensive
confirmed?
FOLLOW-UP No 4
• Advise optimal Patient has
EVALUATION
lifestyle habits elevated BP
• Repeat BP screening Assess for:
in 1 year • Secondary causes
• Target organ damage
A Non-pharmacological (TOD)
therapy
• Other cardiovascular
• Patient education (CV) risk factors or
• Lifestyle modification concomitant
• Continue to measure disorders that would
BP every 3-6 months affect prognosis
3
RISK
GOAL OF STRATIFICATION
Yes THERAPY No
& TREATMENT
Target BP See next page
achieved?
FOLLOW-UP 4
• Repeat BP EVALUATION
screening annually
Assess for:
• Secondary causes
• Other CV risk factors
or concomitant
disorders that would
affect prognosis
DRUG
THERAPY
See page 3
B158
RISK STRATIFICATION
OF HYPERTENSIVE
PATIENTS
5
Low risk or BP RISK High &
130-139/80- STRATIFICATION Very high
89 mmHg w/ risk* or BP
estimated 10-year What is the patient’s risk for ≥140/90
CVD risk <10% developing a major mmHg
CV event?
HYPERTENSION
A Non-pharmacological Moderate risk or BP A Non-pharmacological
therapy 130-139/80-89 mmHg therapy
• Patient education w/ estimated 10-year • Patient education
• Lifestyle modification CVD risk ≥10% • Lifestyle modification
• Monitor BP B Pharmacological
(every 3-6 months) & therapy
risk factors A Non-pharmacological therapy Evaluate BP in 1 month
• Patient education
• Lifestyle modification
• Monitor BP & risk factors
3 • See Drug Therapy on next page
Evaluate BP in 1 month DRUG
GOAL OF THERAPY
THERAPY See next page
Target BP
achieved?
No Yes 3
GOAL OF
THERAPY
Target BP
achieved?
DRUG Yes No
THERAPY
See next page
CONTINUE TO CONTINUE TO • Emphasize lifestyle

MONITOR BP & REASSESS BP & & medication
RISK FACTORS RISK FACTORS compliance
PERIODICALLY EVERY • Consider changing
3-6 MONTHS treatment regimen
*For patients w/ very high BP (eg SBP ≥180 mmHg or DBP ≥110 mmHg), prompt treatment w/ antihypertensives after evaluation is
recommended. Please see Hypertensive Crisis disease management chart for further information.
B159
DECISION TO START
DRUG THERAPY IS MADE
6
THERAPY
DECISION
What is the appropriate
treatment
strategy?
HYPERTENSION
TREATMENT OPTIONS
• Set BP goal & initiate antihypertensive agents based on age, presence of
comorbidities (eg diabetes mellitus & chronic kidney disease)
• Select initial treatment strategy*:
- Start monotherapy w/ any of the 1st-line agents, eg ACEI or ARB, calcium
antagonist & thiazide/thiazide-like diuretic
- Maximize first drug prior to adding a second medication or
- Add a second drug prior to reaching maximum dose of the first drug
- Start w/ 2 1st-line agents from separate drug classes, eg ACEI or ARB w/
calcium antagonist or thiazide/thiazide-like diuretic (either separately or in a
fixed-dose/single-pill combination)
3
CONTINUE
GOAL OF CURRENT
THERAPY Yes
TREATMENT &
Target BP MONITORING
achieved?
No
• Emphasize lifestyle & medication compliance

• Titrate doses of initial medications to maximum or
• Add a third drug class not previously chosen, eg ACEI or ARB
w/ calcium antagonist & thiazide/thiazide-like diuretic
(preferably as a triple-drug single-pill combination)
Target BP reached?
No Yes
• Continue to emphasize lifestyle & CONTINUE CURRENT

medication compliance Yes TREATMENT &
• Add a third drug class not previously Target BP MONITORING
chosen (preferably as a triple-drug reached?
single-pill combination) or
• Add additional class (eg beta-blocker) No C Resistant hypertension
*Consider adding a beta-blocker to any treatment step when specifically indicated, eg atrial fibrillation, angina, heart failure, post-MI,
or young women planning to get pregnant or are pregnant.
B160
1 PRIMARY CARE VISIT

Patient Evaluation
History
• History should be taken w/ emphasis on hypertension, diabetes mellitus (DM), dyslipidemia & premature
coronary heart disease (CHD), stroke or renal disease
- Level & duration of elevated BP
- Usual range of BP; current/past antihypertensive medications & history of adherence to treatment
- Symptoms of secondary causes of hypertension (eg sweating, headache & palpitations in pheochromocytoma;
muscle weakness & tetany in hyperaldosteronism; hypersomnolence & snoring in obstructive sleep apnea;
heat intolerance, weight loss & palpitations in hyperthyroidism; fatigue, edema, & frequent urination in
kidney disease or failure)
- Lifestyle & environmental evaluation (eg dietary intake of fat, salt & alcohol, physical activity, smoking status,
weight gain since young adulthood)
- Medication history of prescribed & over-the-counter medications, use of herbal supplements & illicit drugs
- History or current symptoms of target organ damage (TOD) (eg CHD, cerebrovascular disease, cognitive dysfunction)
- The association between BP & cardiovascular disease (CVD) in Asians is stronger than in Westerners w/
HYPERTENSION
stroke (eg hemorrhagic stroke) & nonischemic heart failure being the common end results of hypertension-
related CVD
- History or current symptoms of concomitant diseases that will affect prognosis (eg DM, renal disease, gout,
UTI, thyroid disease, etc)
- Family history of high BP, stroke, diabetes, CVD, CHD, renal disease & dyslipidemia
- Occupational history (eg w/ frequent travels or long trips, consider time changes, medication schedule,
prevention of complications, etc)
Physical Exam
• Appropriate BP measurement w/ verification in contralateral arm
• Calculation of body mass index (BMI) & waist circumference - risk for metabolic syndrome or for type 2 DM
is high when waist circumference is >102 cm in men, >88 cm in women
• Heart rate (patient at rest) to search for arrhythmias, respiratory rate, temperature
• Examination of optic fundi
• Auscultation for carotid, abdominal & femoral bruits
• Thorough exam of heart & lungs; palpation of the thyroid gland
• Exam of the abdomen for truncal obesity, enlarged kidneys, masses, distended urinary bladder & abnormal
aortic pulsation
• Palpation of lower extremities for edema & pulses, eg ankle-brachial index (ABI)
• Neurological & mental status assessment
Diagnostic Tests
• Should be done to exclude secondary causes, provide evidence for additional risk factors & note the occurrence
of TOD
- CBC, urinalysis, renal function tests, fasting blood sugar &/or HbA1c, lipid profile (after 9- to 12-hour fast),
serum creatinine, serum K & Na, serum uric acid, liver function tests (LFTs), thyroid stimulating hormone,
12-lead ECG, echocardiography
Presence of Secondary Cause or Evidence of TOD
• Consider to screen for secondary hypertension in the following: Abrupt development of hypertension, onset
of hypertension in patients <40 years old, onset of diastolic hypertension in patients ≥65 years old, hypertension
that is either drug-resistant or accelerated/malignant, exacerbation of a previously controlled hypertension,
TOD that is out of proportion to the degree of hypertension, excessive or unprovoked hypokalemia
• Patient should be referred to a specialist & treated appropriately if a secondary cause of hypertension is found
• Further tests should be done if TOD is found in order to evaluate the level of severity
2 DIAGNOSIS
Clinical/Office BP Measurement
• BP is measured at least annually in ≥18 years old but more frequently in those at moderate or high risk of
vascular disease
• Patient should be seated comfortably for >5 minutes in a chair, w/ back supported, feet on the floor & arm
supported at heart level prior to measurement of BP
- Measurement of BP in the standing position is recommended for patients at risk of postural hypotension,
patients w/ diabetes & at the 1st visit of elderly patients
• 2-3 measurements should be taken spaced by 1-2 minutes
- A difference of >15 mmHg between 2 arms suggest arterial problems & requires further investigation
- Take BP measurements from sitting, lying, & standing (usually after 1 minute) positions to take note of drops in BP
• Cuff w/ bladder 12-13 cm wide & 35 cm long should be used & placed at heart level of the patient
- Wider cuffs (>32 cm circumference) are needed for large arms & smaller cuffs (<26 cm circumference) for
thin arms1
- Bladder length should encircle at least 80% of the arm while the width should be at least 40% of arm
circumference
• Use the appearance of phase I Korotkoff ’s sounds for systolic blood pressure (SBP) & the disappearance of
phase V for diastolic blood pressure (DBP)
1Please also refer to the Recommended Cuff Sizes table under Non-pharmacological Therapy on page 9.
B161
2 DIAGNOSIS (CONT'D)
Clinical/Office BP Measurement (Cont'd)
Confirmation of Hypertension
• In general, diagnosis is confirmed by taking the BP 1-4 weeks after the first measurement or the average of
readings on ≥2 occasions or visits
• A substantially elevated BP requires a shorter interval between visits, depending on the degree of BP elevation
& presence of CVD or TOD
Out-of-Office BP Measurement
• Recommended for the confirmation of hypertension diagnosis
• Ambulatory BP Monitoring (ABPM)
- Preferred method; automatically measures patient’s BP at regular intervals over a 24-hour period
- Advantages: Detects masked/white coat hypertension; determines nocturnal BP patterns; confirms borderline
hypertension or abnormal home BP monitoring results; evaluates impact of antihypertensive treatments
• Home BP Monitoring (HBPM)
HYPERTENSION
- Self-measurement of BP for over 5-7 days, if possible in duplicate measurement

- May also be used to screen for masked/white coat hypertension
- Possible error in measurement & no nocturnal BP readings
• In Asians, out-of-office BP management includes focusing initially on the morning BP then nocturnal BP
- Morning hypertension confers CV risk independent of the 24-hour ambulatory BP
- It may be controlled w/ the use of long-acting antihypertensive agents given in appropriate (often full)
doses & in proper combinations; consider bedtime dosing if morning BP is not controlled
- Also, the detection & management of masked & masked uncontrolled hypertension are important parts of
hypertension treatment
BP LEVELS DEFINING HYPERTENSION
2017 ACC/AHA* 2018 ESH/ESC**
Category
SBP (mmHg) &/or DBP (mmHg) SBP (mmHg) &/or DBP (mmHg)
Clinic/Office BP ≥130 ≥80 ≥140 ≥90
Daytime ABPM ≥130 ≥80 ≥135 ≥85
Nighttime ABPM ≥110 ≥65 ≥120 ≥70
24-hour ABPM ≥125 ≥75 ≥130 ≥80
Home BP ≥130 ≥80 ≥135 ≥85
Reference: Bakris G, Ali W, Parati G. ACC/AHA versus ESC/ESH on hypertension guidelines: JACC guideline comparison. J Am
Coll Cardiol. 2019 Jun 18;73(23):3018-3026.
Classification of BP
• Classification must be based on the average of ≥2 properly measured, seated BP readings on each of ≥2 office visits
• Various consensus guidelines are available as standard references for the definition of hypertension1
BP Classification based on 2017 ACC/AHA/AAPA/ SBP (mmHg) DBP (mmHg)

ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA*
Normal <120 & <80
Elevated 120-129 & <80
Hypertension Stage 1 130-139 or 80-89
Hypertension Stage 2 ≥140 or ≥90
BP Classification based on 2018 ESH/ESC** SBP (mmHg) DBP (mmHg)

Optimal <120 & <80
Normal 120-129 &/or 80-84
High Normal 130-139 &/or 85-89
Grade 1 hypertension 140-159 &/or 90-99
Grade 2 hypertension 160-179 &/or 100-109
Grade 3 hypertension ≥180 &/or ≥110
Isolated systolic hypertension (ISH)2 ≥140 & <90
1Recommendations may vary between countries. Please refer to available guidelines from local health authorities.
*Reference: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention,
detection, evaluation, and management of high blood pressure in adults. This guideline updates prior JNC reports.
**Reference: 2018 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the
management of arterial hypertension.
2Graded 1, 2 or 3 according to the SBP values in the indicated ranges.
B162
3 GOALS OF THERAPY
Treatment Goals
• To manage hypertension
- To achieve & maintain BP goal based on age & presence/absence of comorbidities [eg DM & chronic kidney
disease (CKD)]
• To prevent complications through identification & management of all other identified risk factors for CVD
(DM or glucose intolerance, lipid disorders, obesity, smoking)
- Identification & treatment of all reversible risk factors
- Management of concomitant disorders (eg DM, established CV or renal disease)
Target BP1
• Reduce BP to <140/90 mmHg in all patients
• If therapy is well tolerated, a treated BP goal of ≤130/80 mmHg is recommended for:
- Patients w/ clinical CVD or ≥10% atherosclerotic CVD (ASCVD) risk in 10 years
- Patients without clinical CVD & <10% ASCVD risk in 10 years
- Patients w/ comorbidities such as DM, CKD, heart failure, stable ischemic heart disease, atrial fibrillation
HYPERTENSION
on anticoagulation, peripheral vascular disease (PVD) & for secondary stroke prevention
• An SBP goal of 130-139 mmHg is recommended for patients ≥70 years old receiving antihypertensive therapy
- In patients ≥80 years old, an SBP goal of <150 mmHg is advised though it should be adjusted to individual
tolerability in frail elderly patients
• An SBP goal of 120-130 mmHg in most patients ≤69 years old receiving antihypertensive therapy is
recommended
• A DBP goal of <80 mmHg should be considered in all patients regardless of risk level & comorbidities
1Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities.
4 EVALUATION
• If patient is found to have chronic elevated BP, then they should undergo further assessment to determine
secondary causes, TOD, CVD risk factors or concomitant disorders that will affect prognosis
Identifiable Secondary Causes of Hypertension
• CKD
• Chronic steroid therapy & Cushing syndrome
• Coarctation of the aorta
• Obesity
• Takayasu arteritis
• Pheochromocytoma
• Primary aldosteronism
• Renovascular disease
• Obstructive sleep apnea
• Thyroid & parathyroid disorders
• Congenital adrenal hyperplasia
• Alcohol- or drug-induced
- Prescription, over-the-counter medications, herbal supplement, use of illicit drugs, etc
CVD Risk Factors
• Increased age
• Male sex
• Smoking
• Unhealthy diet/physical inactivity
• Low educational or socioeconomic status
• DM
• Overweight or obesity
• Dyslipidemia
• Hyperuricemia
• Metabolic syndrome
• Obstructive sleep apnea
• CKD
• Psychosocial stress
• Family history of premature CV disease (<55 years for male relative or <65 years for female relative)
• Abdominal obesity [waist circumference: Men ≥90 cm; women ≥80 cm (Asian)]
• Early-onset menopause
Target Organ Damage (TOD)
• Heart: LV hypertrophy, angina/prior MI, prior coronary revascularization, heart failure
• Brain: Stroke or transient ischemic attack (TIA), dementia
• Kidney: CKD
• Vascular: Peripheral arterial disease
• Eyes: Retinopathy
B163
• All patients should be classified not only in relation to stages of hypertension but also in terms of total CV risk
resulting from coexistence of different risk factors, organ damage & related diseases
• Decisions on management of hypertension & subsequent follow-up should be based on BP levels along w/
other CV risk factors & TOD
• A study revealed that in patients being given aggressive antihypertensive therapy, prolonged QRS duration
confers higher risk of sudden cardiac death in this subset of patients
• SBP is better in quantifying prognosis than DBP in patients >50 years old
- In younger patients without comorbidities, DBP is a more important CV risk factor
• Pulse pressure is also a good predictor of CV events in elderly patients
• To estimate the 10-year risk of ASCVD, the ACC/AHA pooled cohort equations (http://tools.acc.org/ASCVD-
Risk-Estimator/) or the Systemic COronary Risk Evaluation (SCORE) system may be used
- ASCVD was defined as 1st CHD death, fatal or non-fatal stroke, or non-fatal MI
HYPERTENSION
RISK STRATIFICATION TO QUANTIFY PROGNOSIS

No other TOD, CKD Established CVD,
Blood pressure 1-2 risk ≥3 risk
risk Grade 3 or DM CKD Grade ≥4
(mmHg) factors factors
factors without TOD or DM w/ TOD
SBP 130-139 or Low risk Low risk Low to Moderate to Very High
DBP 85-89 Moderate High risk risk
risk
SBP 140-159 or Low risk Moderate Moderate to High risk Very High
DBP 90-99 risk High risk risk
SBP 160-179 or Moderate Moderate to High risk High risk Very High
DBP 100-109 risk High risk risk
SBP ≥180 or High risk High risk High risk High to Very Very High
DBP ≥110 High risk risk
Reference: 2018 European Society of Hypertension/European Society of Cardiology Guidelines for the management of arterial
hypertension.
6 THERAPY DECISION
General Principles
Initiating Treatment1
• Decision to initiate therapy is based on the untreated BP level & presence of TOD or concomitant disorders
• Primary prevention is recommended for patients:
- Without prior history of CVD but w/ a ≥10% estimated 10-year ASCVD risk & SBP ≥130 mmHg or DBP
≥80 mmHg
- Without prior history of CVD but w/ a <10% estimated 10-year ASCVD risk & SBP ≥140 mmHg or DBP
≥90 mmHg
• Secondary prevention of recurrent CVD events is recommended in patients w/ clinical CVD & SBP ≥130
mmHg or DBP ≥80 mmHg
• Implement lifestyle changes throughout management
- A defined time period of lifestyle changes may be considered in patients w/ medication intolerance &
<10% 10-year ASCVD risk
- Medication is started together w/ lifestyle changes in patients w/ elevations in SBP of >20 mmHg or DBP
of >10 mmHg above BP goal, those w/ TOD on screening & in fit patients 65-80 years old w/ SBP
140-159 mmHg if therapy is well tolerated
- In patients w/ BP ≥140/90 mmHg at low-moderate risk & no TOD, pharmacological therapy can be
started if still hypertensive despite lifestyle changes for 3-6 months
• If w/ high-normal BP, consider initiating drug treatment in very high risk patients w/ CVD, especially CAD
• Pharmacological therapy is recommended in fit patients >80 years old w/ an SBP of ≥160 mmHg & have
not received BP treatment provided therapy is well tolerated
• Start drug treatment promptly in all patients for whom it is necessary to achieve a more rapid control of BP
1Recommendations for treatment initiation may vary between countries. Please refer to available guidelines from local health authorities.
B164
6 THERAPY DECISION (CONT’D)

Treatment Regimen
• Assessment of BP & adjustment of treatment regimen is continuous until BP goal is reached
• Different initial strategies may be considered based on individual circumstances, preferences of physician &
patient:
- Monotherapy
- Though most patients will need >1 drug to achieve BP control, it is reasonable to start w/ a single
antihypertensive agent in low-risk patients w/ low baseline BP that is close to recommended goal (SBP
<150 mmHg), high-risk patients w/ high-normal BP, frail or old patients who need gentle BP reduction,
or those who have a history or are at risk of hypotension or drug-associated side effects
- Dosage titration & sequential addition of other agents may be done to achieve target BP
- Combination therapy
- Two 1st-line agents from separate drug classes, either separately or in a fixed-dose or single-pill
combination
- Recommended in patients w/ an average BP of >20/10 mmHg above their target
HYPERTENSION
- It has been shown in the general population of individuals w/ hypertension that combination therapy at
low dose is more effective than monotherapy at maximal dose
- If goal BP cannot be achieved using 2 drugs, increase treatment to a 3-drug combination therapy
(preferably in a single-pill combination)
• Initial doses of drugs should be at least half the maximum dose so only one dose adjustment is needed to
be done thereafter
• In general, an effective regimen is expected to be reached within 6-8 weeks, regardless whether 1, 2 or 3
drugs were employed
- Consider stepping down therapy if patient's BP remains controlled after 1-2 years of therapy & is without
symptoms related to hypertension or TOD
• Referral to a hypertension specialist may be necessary when goal BP cannot be achieved despite above
strategies or when managing patients for whom additional consultation is warranted
Choice of Antihypertensive Agents
• Choice is influenced by the following factors:
- Patient’s age, ethnicity/race
- Patient’s previous history w/ antihypertensive medications
- Monitor for adverse reactions to avoid patient’s noncompliance to medications
- Presence of other medical conditions
- Eg coronary diseases, DM, renal disease, pregnancy, thiazide
- Possibility of drug interactions w/ drugs used for other conditions
- Patient preference
- Cost (affordability) & availability of the drugs
- Cost consideration should not predominate efficacy & tolerability
• Long-acting drugs or preparations providing 24 hours of efficacy that can be given once daily are preferred
- Improves compliance & minimizes BP variability
- Once-daily drugs can be taken at any time during the day (either morning or evening)
• When >1 drug is needed, the use of a combination product (≥2 appropriate medications in a single tablet)
can simplify the regimen & improve adherence of patients
Patient Education
High Normal or Elevated Blood Pressure
• Warn patients w/ high normal or elevated BP that they are at high risk for developing hypertension
• Inform them that lifestyle modification may reduce this risk
• Advise those w/ DM & kidney disease that they are candidates for drug therapy if lifestyle modification fails
to decrease their BP to goal
• Periodic follow-up (eg every 3-6 months) is recommended to detect & treat hypertension as early as possible
All Patients
• Patients need to be highly motivated to establish & maintain a healthy lifestyle & to take prescribed
antihypertensive medications
• If diagnosis of hypertension is not made, measure the patient’s clinic BP at least annually thereafter
- More frequent BP measurement for patients whose clinic BP is close to 130/80 mmHg
• Encourage measuring BP at home
- In Asians, strict 24-hour BP control starting w/ HBPM is important
• Patients should be made aware that lowering BP can decrease death from stroke, coronary events, HF, along
w/ decreasing the progression of renal failure
- All causes of mortality can be reduced w/ effective antihypertensive management
• Work w/ the patient to establish the goal of therapy
• The patient’s cultural beliefs may influence their attitude & the physician needs to be sensitive when handling
these issues
B165

Patient Education (Cont'd)
BP Measurement & Monitoring
• Before taking BP measurements, advise patients to:
- Avoid exercise, caffeine intake & smoking 30 minutes prior to measurement
- Remove any clothing that can hinder cuff placement
- Make sure the logbook is within reach
- Make sure all devices to be used are working properly (tubes, cuff, batteries, stethoscope)
- Avoid crossing legs, talking & any sudden movements during the measurement
• Advise patients about different BP measuring devices:
- Make sure devices to be used are professionally validated annually
- Devices that measure BP from the brachial artery are preferred than those that read from distal sites (fingers, wrists)
- Electronic/digital BP devices are preferred to be used
- Patients & caregivers should be well trained in using an aneroid BP device; advise patients to have their
HYPERTENSION
mercurial/aneroid apparatus checked every 1-2 years & every 6 months for electronic devices
• Inform patients about appropriate cuff sizes (refer to table below)
RECOMMENDED CUFF SIZES
Arm Circumference Description Cuff Size
22-26 cm Small Adult 12x22 cm

27-34 cm Adult 16x30 cm
35-44 cm Large Adult 16x36 cm
45-52 cm Adult Thigh 16x42 cm
• Instruct patients on how to do self-measurement/monitoring of BP. Advise them to:
- Measure at the same time in the morning & evening
- Find a quiet room w/ a comfortable chair
- Rest for at least 5 minutes before taking BP measurement
- Sit down w/ back supported, feet on the floor, arm supported horizontally, & BP cuff at the level of the heart
- When using a sphygmomanometer, slowly inflate the cuff while palpating the brachial artery. When the pulse
disappears (SBP), slowly deflate the cuff, taking note when the pulse reappears (DBP)
- Now w/ the use of a stethoscope, reinflate the cuff 20 mmHg above the previous SBP, then deflate the cuff
by 1-2 mmHg/sec. Inform the patient that when a tapping sound is heard, this is the SBP, & when it disappears,
this is the DBP
- Follow instructions on how to use electronic devices properly. Stay still while the apparatus takes the BP
reading
- Wait for 1-2 minutes, then take another BP measurement
- Write the results in the logbook immediately after each reading
Lifestyle Modifications
• Considered the cornerstone of hypertension prevention & treatment
• BP-lowering effects can be equivalent to drug monotherapy; major drawback is diminishing patient compliance
over time
• Effects include:
- Prevention or delay of hypertension among nonhypertensive individuals
- Prevention of or delay in the use of drug therapy among those in stage 1 or grade 1 hypertension
- Contribute to BP reduction among hypertensive patients already on drug therapy, allowing for the reduction
of the doses & number of antihypertensive agents
• May also contribute to the control of other medical conditions & CV risk factors
• Annual follow-up is recommended to detect & treat hypertension as early as possible
Weight Reduction & Maintenance
• Helpful in treating hypertension, DM & lipid disorders, especially among overweight or obese patients
- Weight loss of ≥5% in overweight or obese patients is significant
• Maintenance of a healthy body weight (BMI of about 23 kg/m2) & waist circumference (<90 cm in men;
<80 cm in women)
- SBP is reduced by 1 mmHg w/ a weight loss of 1 kg from baseline
• Should use a multidisciplinary approach that includes regular exercise & appropriate diet
- Increase intake of polyunsaturated fatty acids & decrease total & saturated fat
• Weight loss & exercise are recommended in patients also because of the relationship between obesity &
obstructive sleep apnea
- Continuous positive airway pressure (CPAP) therapy may also be used to reduce obstructive sleep apnea
B166

Lifestyle Modifications (Cont'd)
Salt Restriction
• Asians have a higher salt sensitivity, even w/ higher intake of salt & mild obesity
• There is evidence that a causal relationship between BP & salt intake exists
- Excessive salt intake may contribute to resistant hypertension
- Mechanisms include increasing peripheral vascular resistance & extracellular volume
• A daily intake of 5-6 g of salt is recommended for the general population; optimal goal is <1.5 g/day
- Studies have shown that a salt reduction to about 5 g/day results in a modest (1-2 mmHg) SBP-lowering
effect among normotensive individuals while this effect is more pronounced (4-5 mmHg) among hypertensive
individuals
• Effects of salt reduction is seen more among older people, among black population, & in patients w/ metabolic
syndrome, DM or CKD
Other Dietary Changes
HYPERTENSION
• Advise patients to follow the Dietary Approaches to Stop Hypertension (DASH) diet & to consume whole grains
& proteins from plant sources, soluble fiber, low-fat dairy products
• Replace traditional diet w/ fresh vegetables & fruits
- Consumption of fruits among overweight patients should be done w/ caution due to possible high carbohydrate
content of some fruits which may promote weight gain
• Potassium supplementation (3.5-5 g/day) is recommended except in patients w/ CKD or patients using drugs
that decrease excretion of potassium
Regular Exercise
• Regular aerobic & resistance exercises can contribute in both in the prevention & management of hypertension,
& in lowering risk of CV morbidity & mortality
• Patients may be advised to engage in at least 30 minutes of moderate-intensity dynamic aerobic exercise
(eg walking, cycling, jogging, swimming) for 5-7 days weekly
Moderate Alcohol Consumption
• Discourage excessive alcohol consumption since great amounts can raise BP
• Limit alcohol consumption:
- Among hypertensive men: To <20-30 g of ethanol/day (<140 g/week or <14 units/week)
- Among hypertensive women: To <10-20 g of ethanol/day (<80 g/week or <8 units/week)
Smoking Cessation
• Since smoking is a major CV risk factor, patients must be advised to stop this habit
• Also a most effective lifestyle measure for preventing CVDs, including myocardial infarction (MI), stroke &
PVDs
ACE Inhibitors (ACEI)
• Block the conversion of angiotensin I to angiotensin II by inhibiting angiotensin-converting enzyme
• ACE inhibitors are suitable for initiation & maintenance of therapy
• Have established clinical outcome benefits in patients w/ chronic heart failure (CHF) & post MI patients w/
reduced LV ejection fraction; also effective in reducing LV hypertrophy & preserving kidney function
• Given as 1st-line agents at maximally tolerated doses to CKD patients w/ urinary albumin-to-creatinine ratio
of ≥30 mg/g (or equivalent)
• Are well-tolerated; most common side effect is dry cough (most common in women & among Asian & African
patients) related to effects of bradykinin or prostaglandin metabolism
• There is a risk of hypotension when starting treatment w/ ACE inhibitors in patients who are already on
diuretics, or are on low-salt diet or are dehydrated
- For patients on diuretics, skipping a dose prior to starting ACE inhibitor may help prevent this sudden drop
in BP
• Should not be combined w/ angiotensin receptor blockers or direct renin inhibitors
• Drug effects do not seem to have dose-dependent effects, except for hyperkalemia which may occur more
frequently w/ high doses
- Allows patient to initiate treatment using medium or even approved high doses
B167

Alpha-Blockers
• Reduce BP by blocking arterial alpha-adrenergic receptors, in effect, preventing the vasoconstrictor actions
of these receptors
• Less widely used as first-line agents due to limited evidence for their clinical outcome benefits
• Are useful in treating resistant hypertension when used in combination w/ other agents such as beta-blockers,
diuretics & ACE inhibitors
• Are beneficial part of treatment regimens for older hypertensive men w/ benign prostatic hypertrophy
• Have favorable effects on blood glucose & lipid levels
Angiotensin II Antagonists (also called Angiotensin Receptor Blockers or ARBs)
• Act by blocking the action of angiotensin II on its AT1 receptors, preventing the vasoconstrictor effects of this
receptor
• Provide the same CV & renal benefits as ACE inhibitors
• Should not be combined w/ ACE inhibitors or direct renin inhibitors
HYPERTENSION
• Are well tolerated; do not cause cough & only rarely cause angioedema
• Drug effects do not appear to have dose-dependent effects
- Allows patient to start w/ medium or even maximum approved doses
• For patients on diuretics, skipping a dose of the diuretic prior to starting ARBs may help prevent sudden drop
in BP
• Can be used to prevent recurrence of atrial fibrillation
Beta-Blockers
• Beta-blockers may be combined w/ any of the other major drug classes at any step of the hypertension treatment
when indicated (eg post MI, heart failure, angina, atrial fibrillation, or young women planning to get pregnant
or are pregnant)
- For patients without conditions warranting beta-blockade, beta-blockers should not be used as initial therapy
• Drug of choice in patients w/ history of MI & heart failure
- Useful in patients w/ effort angina, tachyarrhythmia & have been shown to reduce CV morbidity & mortality
in post-MI patients & risk of exacerbations & mortality in patients w/ chronic obstructive lung disease
- Specified beta-blockers for heart failure include Bisoprolol, Carvedilol, Metoprolol succinate & Nebivolol
• Studies show that Celiprolol, Carvedilol & Nebivolol (3rd generation of beta-blockers) can reduce central pulse
pressure & aortic stiffness as compared to Metoprolol & Atenolol (2nd generation of beta-blockers); Nebivolol
has less effects on insulin sensitivity than Metoprolol
• Act as competitive antagonists of the effects of catecholamines at beta-adrenergic receptor sites
- Beta 2-blockade can increase bronchial resistance & inhibition of catecholamine-induced glucose
metabolism
- Beta-blockers have different affinities for beta1- or beta2-blockade but as doses are increased, activity of beta2
receptors can become apparent in beta1 selective inhibitors
• Combination w/ thiazide diuretic is shown to have dysmetabolic effect & increased incidence of new onset
diabetes among patients & is therefore, not recommended in patients at risk for diabetes
Calcium (Ca) Antagonists
• Act by blocking the inward flow of calcium ions through the L channels of arterial smooth muscle cells
• Ca antagonists are powerful antihypertensive agents, especially when given in combination w/ ACE inhibitors
or w/ ARBs
• Main side effect is peripheral edema, most especially at high doses; though a clinical rather than a laboratory
approach most often is enough to eliminate a renal or hepatic etiology for the edema
- Reduced by combining w/ ACE inhibitors or ARBs
Dihydropyridine Ca Antagonists
• Eg Amlodipine, Cilnidipine, Felodipine, Isradipine, Manidipine, Nicardipine, Nifedipine, Nisoldipine
• Usually used for their antihypertensive & anti-anginal effects
• Dihydropyridines have shown beneficial effects on stroke & CV outcomes in hypertension trials
• Dihydropyridines (but not nondihydropyridines) can be safely combined w/ beta-blockers
• Have greater selectivity for vascular smooth muscle than for myocardium & their main effect is vascular
relaxation
- They have little or no effect at the SA or AV nodes & negative inotropic activity is not typical at therapeutic
doses
B168

Calcium (Ca) Antagonists (Cont'd)
Benzothiazepine & Phenylalkylamine Ca Antagonists (Non-dihydropyridine Ca Antagonists)
• Eg Diltiazem, Verapamil
• Typically used for their antiarrhythmic, anti-anginal & antihypertensive properties
• Tend to have less selective vasodilatory activity than dihydropyridine Ca antagonists
- They have direct effect on myocardium causing depression of SA & AV conduction
• Nondihydropyridines are preferred in patients w/ fast heart rates & rate control for atrial fibrillation patients
who cannot tolerate beta-blockers
• A randomized controlled trial revealed that Verapamil + Trandolapril was as clinically effective as Atenolol +
Hydrochlorothiazide in hypertensive patients w/ coronary artery disease
• Preferred in patients w/ proteinuria due to the additional antiproteinuric effect in Diltiazem & Verapamil
Direct Renin Inhibitors
• Eg Aliskiren
HYPERTENSION
• Found to be as effective as ARBs & ACE inhibitors without dose-related increase in side effects in the elderly;
combination w/ ACE inhibitor or ARB is not recommended
• Current available data show that Aliskiren:
- As monotherapy, lowers systolic BP & diastolic BP in younger & elderly hypertensive patients
- Has a greater BP lowering effect when used in combination w/ a thiazide diuretic, a renin angiotensin blocker
or a Ca antagonist
- Prolonged use in combination treatment can have a favorable effect on asymptomatic organ damage
• Appears well tolerated among patients >75 years of age, including those w/ renal disease (w/ estimated GFR
≥30 mL/min/1.73 m2)
• Main side effect is mild diarrhea
Diuretics
• Use of diuretics has been well-established in the treatment of hypertension & diuretics are suitable for initiation
& maintenance of therapy
- When used in combination, diuretics may enhance the efficacy of concurrently used antihypertensive drug
- Reduce the risk of fatal & nonfatal stroke & have been shown to reduce CV morbidity & mortality & all-cause
mortality
- Drug of choice in the elderly w/ no comorbid conditions
• Combination treatment w/ potassium-sparing diuretics (eg Amiloride, Triamterene), mineralocorticoid
antagonists (eg Spironolactone, Eplerenone), & epithelial sodium transport channel antagonists w/ other agents
are useful in treating hypertension by reducing vascular stiffness & SBP
• Eg Spironolactone, Eplerenone
• Preferred therapeutic agents for resistant hypertension & primary aldosteronism
• Have recently been part of standard treatment of heart failure
• Can be effective in lowering BP when added to standard 3-drug regimens (ACE inhibitor or ARB/Ca antagonist/
diuretic) in treatment-resistant hypertension after excluding secondary hypertension
Loop Diuretics
• Eg Furosemide, Torasemide, Bumetanide
• Preferred agents in patients w/ symptomatic heart failure
• Loop diuretics are preferred over thiazide diuretics in patients w/ renal insufficiency
Thiazide & Thiazide-like Diuretics
• Eg Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone
• Act by increasing elimination of sodium by kidneys & may have some vasodilator effects
• Most effective in BP reduction when combined w/ ACE inhibitors or ARBs
- Also effective when combined w/ Ca antagonists
• W/ proven clinical outcome benefits in reducing strokes & major CV events
- Chlorthalidone has a longer duration of action & proven reduction of CVD risk
• It was suggested by some meta-analyses & a large randomized controlled trial comparing first-step agents that
diuretics, especially the long-acting thiazide-like agent Chlorthalidone, may provide an optimal choice for
initial treatment of hypertension
• Main side effects (metabolic, such as hypokalemia, hyponatremia, hyperuricemia, hyperglycemia) are reduced
by lowering the doses or combining them w/ ACE inhibitors
- Used also in combination w/ potassium-sparing diuretic to prevent thiazide-induced hypokalemia
B169

Other Antihypertensives
Centrally Acting Agents
• Eg Clonidine, Methyldopa
• More often used nowadays as part of multiple drug combinations
• Act by reducing sympathetic outflow from the central nervous system
• Methyldopa may be considered in resistant hypertension in combination w/ other antihypertensive agents
- Safe to use in pregnancy
Direct Vasodilators
• Eg Hydralazine, Minoxidil
• Are most effective in reducing BP when combined w/ diuretics & beta-blockers or sympatholytic agents
• Usually used only as 4th line or later additions to treatment regimens
HYPERTENSION
C RESISTANT HYPERTENSION
• Target BP not achieved & patient treated w/ ≥3 drugs at optimal doses (including a diuretic) or BP <130/80
mmHg but patient treated w/ ≥4 drugs
- For patients not controlled on 3 drugs, maximizing diuretic therapy & adding an aldosterone antagonist (eg
Spironolactone), a beta-blocker, a centrally acting agent, an alpha-blocker, or a direct vasodilator will often be helpful
- If patient is intolerant to Spironolactone, consider additional diuretic therapy, eg Amiloride, Eplerenone, a
loop diuretic or a higher-dose thiazide or thiazide-like diuretic
• If BP is still uncontrolled after 3 drugs at near-max doses, consider the following:
- Inaccurate BP measurements
- Nonadherence to lifestyle modifications
- Noncompliance to treatment regimen
- Drug interactions
- White coat hypertension
- Secondary hypertension
- Complications of long-standing hypertension (eg nephrosclerosis)
• Consider referral to a hypertension specialist if after 6 months of therapy, BP remains uncontrolled
COVID-19 INFECTION & HYPERTENSION

• Continue home BP monitoring; if required, telehealth services (eg phone or video consultation) may be
used to access healthcare providers during the COVID-19 pandemic
• Antihypertensive therapy should follow current guideline recommendations
- Risk of COVID-19 infection or risk of developing severe COVID-19 complications is not increased w/ prior
or current treatment w/ ACE inhibitors or ARBs thus treatment should be continued as prescribed
- Treatment may be withdrawn temporarily in patients who develop hypotension or acute kidney injury from
severe COVID-19 infection
- Parenteral antihypertensive medications are necessary for patients w/ persistent severe hypertension requiring
invasive ventilation
• Monitor for arrhythmias in hypertensive patients w/ cardiac disease & for hypokalemia in those w/ severe
COVID-19 infection
B170
INDICATIONS & PREFERRED ANTIHYPERTENSIVE TREATMENT

Indication Preferred Antihypertensives
Angina pectoris • Beta-blocker • Ca antagonist
Asymptomatic • ACE inhibitor • Ca antagonist
atherosclerosis
Atrial fibrillation Recurrent: Permanent:
• Angiotensin II antagonist • Beta-blocker
• ACE inhibitor • Ca antagonist
• Beta-blocker (Non-dihydropyridine)
• Aldosterone antagonist
DM Combination of ≥2 drugs are typically needed to reach target BP
• ACE inhibitor • Beta-blocker
HYPERTENSION
• Angiotensin II antagonist • Thiazide diuretic
• Ca antagonist
Heart failure Asymptomatic patients w/ ventricular dysfunction:
• ACE inhibitor
Symptomatic ventricular dysfunction or end-stage heart disease:
• ACE inhibitor • Aldosterone antagonist
• Angiotensin II antagonist • Beta-blocker
• Angiotensin • Diuretic
receptor-neprilysin inhibitor
ISH (elderly) • Diuretics • Ca antagonist
• ACE inhibitor • Direct renin inhibitor
• Angiotensin II antagonist
LV hypertrophy • Angiotensin II antagonist • Ca antagonist
• ACE inhibitor • Diuretic
Metabolic syndrome • ACE inhibitor • Ca antagonist
Microalbuminuria • ACE inhibitor • Direct renin inhibitor
Peripheral arterial disease • Ca antagonist • ACE inhibitor
• Beta-blocker (if w/ arterial
hypertension)
Post MI • ACE inhibitor • Angiotensin II antagonist
• Aldosterone antagonist • Beta-blocker
Post stroke • ACE inhibitor • Ca antagonist
• Angiotensin II antagonist • Thiazide-like diuretic
Proteinuria/End-stage renal • ACE inhibitor • Angiotensin II antagonist
disease • Loop diuretics • Ca antagonist
Effective Antihypertensive Combinations

Combination therapy can be initiated in hypertension stage 2 & above or hypertension within those at higher risk
for CVD. In 15-20% of hypertensive patients, BP control cannot be achieved w/ a two-drug combination; in this
case, a three-drug combination may be used, preferably in a fixed-dose or single-pill combination
• ACE inhibitor or angiotensin II antagonist + Ca antagonist &/or diuretic
• ACE inhibitor or angiotensin II antagonist + Ca antagonist &/or beta-blocker
• Ca antagonist + beta-blocker or diuretic
• Beta-blocker + diuretic
Many antihypertensive combinations are available. Please see the Product Section & the latest MIMS for specific
formulations & prescribing information.
B171
Dosage Guidelines
ACE INHIBITORS1,2
Drug Dosage Remarks
Benazepril Initial dose: 10 mg PO 24 hrly Adverse Reactions
Maintenance: 20-40 mg/day PO • CV effects (hypotension, angioedema);
Max dose: 40-80 mg/day CNS effects (fatigue, headache); GI effects
(taste disturbances, N/V); Resp effects
Captopril Initial dose: 12.5 mg PO 12 hrly (persistent dry cough; upper resp tract
May increase gradually at 2-4 wk intervals symptoms); Dermatologic effects (skin
Maintenance: 50 mg PO 12 hrly rashes, erythema multiforme, toxic
Max dose: 150 mg/day epidermal necrolysis); Hypersensitivity
HYPERTENSION
reactions; Renal effect (renal impairment);

Cilazapril Initial dose: 1 mg PO 24 hrly Electrolyte disturbances (hyperkalemia,
May adjust dose once every 2-4 wk hyponatremia); Blood disorders
Maintenance dose: 2.5-5 mg PO 24 hrly Special Instructions
Max dose: 10 mg/day • Patients w/ HF & those who may be salt
Delapril Initial dose: 15 mg PO 24 hrly or water depleted (taking diuretic or on
Maintenance dose: 15-30 mg PO 12 hrly dialysis) may experience hypotension
during initial stages of ACE inhibitor
Max dose: 120 mg/day therapy
Enalapril Initial dose (patient taking diuretic): - Start treatment only under close
2.5 mg PO 24 hrly medical supervision; in these patients
Initial dose (patient not on diuretic): 5 mg use a low dose & have the patient in a
PO 24 hrly supine position
Maintenance dose: 10-20 mg PO 24 hrly • Avoid in patients w/ SBP <100 mmHg,
Max dose: 40 mg/day aortic stenosis or outflow tract
obstruction & should generally be avoided
Fosinopril Initial dose (w/ or without diuretic): in suspected or actual renovascular
10 mg PO 24 hrly disease
Maintenance dose: 10-40 mg PO 24 hrly • Avoid in patients w/ history of hereditary
Imidapril Initial dose: 5 mg PO 24 hrly or idiopathic angioedema & in those w/
history of angioedema related to previous
Maintenance dose: 10 mg PO 24 hrly treatment w/ ACE inhibitors
Max dose: 20 mg/day • Renal function should be assessed prior
Lisinopril Initial dose (patient taking diuretic): to administration of ACE inhibitors,
5 mg PO 24 hrly during therapy, & over the first few days
Initial dose (patient not on diuretic): after initiation
5-10 mg PO 24 hrly - Patient w/ renal disease or taking high
Maintenance dose: 20 mg PO 24 hrly doses should be monitored regularly for
Max dose: 80 mg/day proteinuria
Moexipril Initial dose (patient taking diuretic):
3.75 mg PO 24 hrly
Initial dose (patient not on diuretic):
7.5 mg PO 24 hrly
Maintenance dose: 7.5-15 mg PO 24 hrly
(May give dose 12 hrly if control is
inadequate w/ single daily dose)
Max dose: 30 mg/day
1If possible, discontinue diuretics 2-3 wk before initiating therapy w/ ACE inhibitors. Otherwise, monitor patient closely during therapy.

B172
Dosage Guidelines

Drug Dosage Remarks
Perindopril3 Initial dose: 4-5 mg PO 24 hrly Adverse Reactions
May increase to 8-10 mg PO 24 hrly after • CV effects (hypotension, angioedema);
1 mth of treatment CNS effects (fatigue, headache); GI effects
Max dose: 8-10 mg/day (taste disturbances, N/V); Resp effects
(persistent dry cough; upper resp tract
symptoms); Dermatologic effects (skin
rashes, erythema multiforme, toxic
Quinapril Initial dose (patient taking diuretic): epidermal necrolysis); hypersensitivity
HYPERTENSION
5 mg PO 24 hrly reactions; Renal effect (renal impairment);
Initial dose (patient not on diuretic): Electrolyte disturbances (hyperkalemia,
10-20 mg PO 24 hrly hyponatremia); Blood disorders
Maintenance dose: 20-40 mg/day Special Instructions
Max dose: 80 mg/day • Patients w/ HF & those who may be salt
or water depleted (taking diuretic or on
dialysis) may experience hypotension
during initial stages of ACE inhibitor
Ramipril Initial dose: 1.25-2.5 mg PO 24 hrly therapy
Maintenance dose: 2.5-5 mg PO 24 hrly - Start treatment only under close
Max dose: 10 mg/day medical supervision; in these patients
use a low dose & have the patient in a
supine position
• Avoid in patients w/ SBP <100 mmHg,
Trandolapril Initial dose (patient not on diuretic):
aortic stenosis or outflow tract
1 mg PO 24 hrly
obstruction & should generally be avoided
Initial dose (patient taking diuretic): in suspected or actual renovascular
0.5 mg PO 24 hrly disease
Maintenance dose: 1-2 mg PO 24 hrly • Avoid in patients w/ history of hereditary
Max dose: 4 mg/day or idiopathic angioedema & in those w/
history of angioedema related to previous
treatment w/ ACE inhibitors
Zofenopril Initial dose: 15 mg PO 24 hrly • Renal function should be assessed prior
to administration of ACE inhibitors,
May increase dose at 4-wk intervals during therapy, & over the first few days
Usual effective dose: 30 mg PO 24 hrly after initiation
Max dose: 60 mg/day, administered in - Patient w/ renal disease or taking high
single or two divided doses doses should be monitored regularly for
If diuretic cannot be discontinued prior to proteinuria
initiation of therapy, initial dose should be
7.5 mg daily
3Combination w/ Bisoprolol is available.

B173
Dosage Guidelines

Drug Dosage Remarks
Other Combinations
Perindopril/ Perindopril 5 mg/Indapamide 1.25 mg/ Adverse Reactions
Indapamide/ Amlodipine 5 mg or • CNS effects (severe dizziness, fainting,
Amlodipine Perindopril 5 mg/Indapamide 1.25 mg/ headache, cramps, somnolence,
Amlodipine 10 mg or lightheadedness); Resp effects (cough,
Perindopril 10 mg/Indapamide 2.5 mg/ shortness of breath); Other effects (vision
Amlodipine 5 mg or disturbances, tinnitus, GI disorders,
allergic reactions, ankle swelling,
HYPERTENSION
Perindopril 10 mg/Indapamide 2.5 mg/

Amlodipine 10 mg palpitations, flushing)
• Use w/ caution in patients w/ hypertrophic
cardiomyopathy, heart failure, hypertensive
crisis, hepatic impairment, collagen
diseases, atherosclerosis, gout, diabetes,
photosensitivity reactions, renal
impairment, metabolic acidosis, cerebral
circulatory insufficiency, hypovolemia;
patients undergoing hemodialysis, anesth
&/or surgery, desensitization treatment,
race (black patients)
• Combination w/ Lithium, Aliskiren,
K-sparing drugs, K supplements or
K-containing salt substitutes is not
recommended
• Monitor regularly plasma electrolytes, K, Ca
levels; if angioedema occurs, stop treatment
immediately
• Avoid in patients w/ symptoms of
angioedema w/ previous ACE inhibitor
treatment or hereditary/idiopathic
angioedema, severe liver disease, untreated
decompensated heart failure,
non-antiarrhythmic medicines causing
torsade de pointes, aortic stenosis or
cardiogenic shock, heart failure after a heart
attack, severe hypotension, low blood K,
severe renal impairment, dialysis; patients
w/ DM & kidney problems treated w/
Aliskiren

B174
Dosage Guidelines

Drug Dosage Remarks
Other Combinations (Cont'd)
Perindopril/ Perindopril 5 mg/Amlodipine 5 mg/ Adverse Reactions
Amlodipine/ Atorvastatin 10 mg • GI effects (constipation, dyspepsia, N/V,
Atorvastatin Perindopril 5 mg/Amlodipine 5 mg/ diarrhea); CNS effects (headache,
Atorvastatin 20 mg dizziness, paresthesia, asthenia);
Perindopril 10 mg/Amlodipine 5 mg/ Musculoskeletal effects (myalgia,
Atorvastatin 20 mg arthralgia, back pain, joint & ankle
swelling); Metabolic effects
HYPERTENSION
Perindopril 10 mg/Amlodipine 10 mg/
Atorvastatin 20 mg (hyperglycemia, abnormal LFT, increased
blood creatinine); CV effects
Perindopril 10 mg/Amlodipine 10 mg/ (palpitations, hypotension); Other effects
Atorvastatin 40 mg (nasopharyngitis, hypersensitivity,
1 tab PO 24 hrly epistaxis, flushing, edema, visual
impairment, tinnitus, cough, dyspnea,
rash, pruritus)
• Use w/ caution in patients w/ collagen
vascular disease, on immunosuppressant
therapy, Allopurinol or Procainamide
• Increased risk of hypotension,
hyperkalemia, decreased renal function;
interstitial lung disease on long-term
therapy
• Monitor glycemic control & LFTs
periodically
• Avoid in patients w/ hypersensitivity, liver
disease, severe hypotension,
hemodynamically unstable heart failure,
history of angioedema, significant
bilateral renal artery stenosis; on
Sacubitril/Valsartan

B175
Dosage Guidelines
ALPHA-BLOCKERS
Drug Dosage Remarks
Doxazosin Initial dose: 1 mg PO 24 hrly Adverse Reactions
May increase dose at 1-2 wk intervals to • Postural hypotension which may be severe
2 mg/day PO & then to 4 mg PO 24 hrly after 1st dose & can produce syncope
Max dose: 8-16 mg/day which may be preceded by tachycardia
Prazosin Initial dose: 0.5 mg PO 8-12 hrly • Effects which may diminish after
continued therapy: CNS effects (dizziness,
Increase dose gradually every 3-7 days to: headache, lack of energy); GI effect
Maintenance dose: 3-15 mg/day PO in (nausea); CV effect (palpitations)
divided doses
HYPERTENSION
• Other CV effects (edema, chest pain,

Max dose: 20 mg/day dyspnea); GI effects (constipation, diarrhea,
Terazosin Initial dose: 1 mg PO 24 hrly at bedtime vomiting; dry mouth); CNS effects
Increase dose at 1 wk interval (depression, nervousness, sleep disturbances,
vertigo, hallucinations, paresthesia); Urinary
Maintenance dose: 2-10 mg PO 24 hrly effects (urinary frequency, incontinence);
Max dose: 20 mg/day Ophthalmic effect (blurred vision); Hepatic
effects (abnormal LFTs, pancreatitis); Other
effects (arthralgia, skin rashes, impotence,
priapism)
• Start treatment w/ a low dose, preferably at
night to avoid postural hypotension
• Not recommended for HF treatment in
patients w/ mechanical obstruction
• Use w/ caution in the elderly, in patients w/
renal or hepatic failure or in patients w/
angina
ANGIOTENSIN II ANTAGONISTS1
Drug Dosage Remarks
Azilsartan Initial dose: 40 mg PO 24 hrly Adverse Reactions
medoxomil May increase up to 80 mg PO 24 hrly • Usually mild & transient: CNS effects
Candesartan Initial dose: 8 mg PO 24 hrly (dizziness, headache); CV effect
(dose-related orthostatic hypotension which
Maintenance dose: 8-16 mg PO 24 hrly may occur particularly in patients w/
Max dose: 32 mg/day volume depletion); Renal impairment
Eprosartan 600 mg PO 24 hrly in the morning • Rare effects: Rash, angioedema, elevated
Max dose: 800 mg/day LFTs, myalgia
Fimasartan Initial dose: 60 mg PO 24 hrly
• Patients w/ volume depletion (eg high-dose
diuretic therapy) may experience
Irbesartan Initial dose: 150 mg PO 24 hrly hypotension & should be started on low dose
Maintenance dose: • Use w/ caution in patients w/ renal artery,
150-300 mg PO 24 hrly aortic or mitral valve stenosis, renal or
Max dose: 300 mg/day hepatic impairment
• Serum K should be monitored especially in
the elderly, patients w/ renal impairment, &
K-sparing diuretics should be avoided
1Combinations of angiotensin II antagonist & thiazide diuretic; angiotensin II antagonist & calcium antagonist are available.

B176
Dosage Guidelines
ANGIOTENSIN II ANTAGONISTS1 (CONT’D)

Drug Dosage Remarks
Losartan Initial dose: 50 mg PO 24 hrly Adverse Reactions
Maintenance dose: 50-100 mg PO • Usually mild & transient: CNS effects
24 hrly (dizziness, headache); CV effect
(dose-related orthostatic hypotension
Olmesartan Initial dose: 10-20 mg PO 24 hrly
which may occur particularly in patients
medoxomil May increase to 40 mg PO 24 hrly w/ volume depletion); Renal impairment
Telmisartan 20-40 mg PO 24 hrly • Rare effects: Rash, angioedema, elevated
Max dose: 80 mg/day LFTs, myalgia
HYPERTENSION
Valsartan Initial dose: • Patients w/ volume depletion (eg
80 or 160 mg PO 24 hrly high-dose diuretic therapy) may
May increase to 320 mg PO 24 hrly experience hypotension & should be
started on low dose
• Use w/ caution in patients w/ renal artery,
aortic or mitral valve stenosis, renal or
hepatic impairment
• Serum K should be monitored especially in
the elderly, patients w/ renal impairment, &
K-sparing diuretics should be avoided
Other Combinations
Losartan/ Losartan 50 mg/Amlodipine 5 mg/ Adverse Reactions
Amlodipine/ Hydrochlorothiazide 12.5 mg or • Please see Remarks section of each
Hydrochlorothiazide Losartan 100 mg/Amlodipine 5 mg/ individual drug component
Hydrochlorothiazide 12.5 mg or Special Instructions
Losartan 100 mg/Amlodipine 10 mg/ • Use w/ caution in hypotension in
Hydrochlorothiazide 12.5 mg volume- & salt-depleted patients, patients
1 tab PO 24 hrly, individualize dose w/ severe aortic & mitral valve stenosis,
severe obstructive CAD, obstructive
Olmesartan Olmesartan medoxomil 20 mg/ hypertrophic cardiomyopathy, CHF, renal
medoxomil/ Amlodipine 5 mg/ & hepatic impairment, renal
Amlodipine/ Hydrochlorothiazide 12.5 mg or transplantation, electrolyte imbalances,
Hydrochlorothiazide Olmesartan medoxomil 40 mg/ metabolic & endocrine effects, history of
Amlodipine 5 mg/ allergy or bronchial asthma; activation of
Hydrochlorothiazide 12.5 mg or SLE
Olmesartan medoxomil 40 mg/ • Avoid in patients w/ hypersensitivity to
Amlodipine 10 mg/ Losartan, Olmesartan medoxomil,
Hydrochlorothiazide 12.5 mg Valsartan, Amlodipine,
Individualize dose Hydrochlorothiazide & other
sulfonamide-derived drugs, anuria;
Valsartan/ Valsartan 160 mg/Amlodipine 5 mg/ concomitant use w/ Aliskiren in patients
Amlodipine/ Hydrochlorothiazide 12.5 mg or w/ diabetes
Hydrochlorothiazide Valsartan 160 mg/Amlodipine 5 mg/
Hydrochlorothiazide 25 mg or
Valsartan 160 mg/Amlodipine 10
mg/Hydrochlorothiazide 12.5 mg or
mg/Hydrochlorothiazide 25 mg or
mg/Hydrochlorothiazide 25 mg
1 tab PO 24 hrly
1Combinations of angiotensin II antagonist & thiazide diuretic; angiotensin II antagonist & calcium antagonist are available.

B177
Dosage Guidelines
BETA-BLOCKERS1
Drug Dosage Remarks
Acebutolol Initial dose: Adverse Reactions
200 mg PO 12 hrly or 400 mg PO 24 hrly • CNS effects (fatigue, depression,
May increase to 800 mg PO 24 hrly or dizziness, confusion, sleep disturbances,
400 mg PO 12 hrly after 2 wk headache); CV effects (HF, heart block,
Maintenance dose: coldness of extremities, male impotence,
400-800 mg PO 24 hrly hypotension); Resp effects
(bronchospasm in susceptible patients &
Max dose: 800 mg/day drugs w/ beta1 selectivity should be used
HYPERTENSION
Alprenolol 200 mg PO 24 hrly in divided doses w/ caution); GI effects (N/V, diarrhea,

Atenolol Initial dose: 25-50 mg PO 24 hrly constipation); Metabolic effects (can
produce hyper- or hypoglycemia,
May be gradually increased to changes in serum cholesterol &
50-100 mg PO 24 hrly triglycerides)
Max dose: 100 mg/day • Esmolol: Infusion site reactions, eg
Betaxolol Initial dose: 10-20 mg PO 24 hrly inflammation & induration
May be increased after 1-2 wk to: Special Instructions
Max dose: 40 mg/day • Contraindicated in severe bradycardia,
preexisting high degree of AV block, sick
Bisoprolol2 Initial dose: 2.5-5 mg PO 24 hrly sinus syndrome & severe unstable LV
Maintenance dose: 5-10 mg PO 24 hrly failure
Max dose: 20 mg/day • Use w/ caution in patients w/
bronchospasm, asthma or obstructive
Carteolol 2.5-30 mg PO 24 hrly airway diseases, renal impairment. Use
Adjust according to response w/ caution in 1st-degree block or
Carvedilol Initial dose: 12.5 mg PO 24 hrly x 2 days depressed myocardial contractility,
Then increase to 25 mg PO 24 hrly depression, patients w/ PVD & patients
on Insulin
or
• Beta-blockers may mask the symptoms
Initial dose: 6.25 mg PO 12 hrly of hyperthyroidism & hypoglycemia &
May increase to 12.5 mg PO 12 hrly after may aggravate psoriasis
1-2 wk • Patients on long-term treatment should
Dose may be increased, if necessary, at 2-wk not discontinue abruptly; should
intervals to 50 mg 24 hrly or in divided doses discontinue gradually over 1-2 wk
Max dose: 50 mg/day • Esmolol: Do not use in patients w/
Celiprolol Initial dose: 200 mg PO 24 hrly increased BP due to vasoconstriction
May increase dose to 400 mg PO 24 hrly associated w/ hypothermia as treatment
for HTN
Esmolol Intraoperative HTN
Loading dose: 80 mg (approx 1 mg/kg) IV
bolus over 30 sec followed by 150 mcg/kg/
min infusion, may be increased to
300 mcg/kg/min if necessary
Postoperative HTN
Loading dose: 0.5 mg/kg IV over 1 min
followed by 4-min infusion of 50 mcg/kg/
min. If effect is not observed within 5 min,
repeat same loading dose & follow w/ a
maintenance infusion increased to
100 mcg/kg/min
1Combinations of beta-blocker & thiazide diuretic; beta-blocker & calcium antagonist are available.

B178
Dosage Guidelines
BETA-BLOCKERS1 (CONT’D)
Drug Dosage Remarks
Labetalol Initial dose: 100 mg PO 12 hrly Adverse Reactions
May increase dose after 2 wk to 200-400 mg/ • CNS effects (fatigue, depression,
day PO dizziness, confusion, sleep disturbances,
Max dose: 2400 mg/day headache); CV effects (HF, heart block,
coldness of extremities, male impotence,
Metoprolol Regular release: hypotension); Resp effects
Initial dose: 50-100 mg PO 12-24 hrly (bronchospasm in susceptible patients &
May increase to 100-400 mg/day PO drugs w/ beta1 selectivity should be used
HYPERTENSION
Maintenance dose: 100-200 mg PO 24 hrly w/ caution); GI effects (N/V, diarrhea,
Max dose: 400 mg/day constipation); Metabolic effects (can
produce hyper- or hypoglycemia,
Extended-release: 25-100 mg PO 24 hrly changes in serum cholesterol &
Nadolol Initial dose: 20-40 mg PO 24 hrly triglycerides)
May increase dose by 40-80 mg every Special Instructions
2-14 days until adequate response is achieved • Contraindicated in severe bradycardia,
Maintenance dose: 40-80 mg PO 24 hrly preexisting high degree of AV block,
Max dose: 240-320 mg/day sick sinus syndrome & severe unstable
LV failure
Nebivolol Initial dose: 5 mg PO 24 hrly
• Use w/ caution in patients w/
In renal insufficiency & in patients >65 yr: bronchospasm, asthma or obstructive
Recommended starting dose is 2.5 mg PO airway diseases, renal impairment. Use
24 hrly w/ caution in 1st-degree block or
Oxprenolol Initial dose: 80-160 mg/day PO divided depressed myocardial contractility,
8-12 hrly depression, patients w/ PVD & patients
May increase to 160-320 mg/day PO 1-2 wkly on Insulin
Max dose: 320 mg PO 24 hrly • Beta-blockers may mask the symptoms
of hyperthyroidism & hypoglycemia &
Extended-release: ≤320 mg PO 24 hrly
may aggravate psoriasis
Pindolol2 Initial dose: 5 mg PO 8-12 hrly or 15 mg PO • Patients on long-term treatment should
24 hrly not discontinue abruptly; should
Maintenance dose: 15-45 mg PO 24 hrly in discontinue gradually over 1-2 wk
single or divided doses
Max dose: 60 mg/day
Propranolol Regular release:
May increase to 160-320 mg/day PO divided
6-12 hrly wkly
Extended-release:
May increase to 120-160 mg PO 24 hrly
1Combinations of beta-blocker & thiazide diuretic; beta-blocker & calcium antagonist are available.
2Combination w/ Clopamide is available.

B179
Dosage Guidelines
CALCIUM ANTAGONISTS1
Drug Dosage Remarks
Benzothiazepine
Initial dose: 30-60 mg PO 8 hrly • CV effects (depression of cardiac function,
or 60-120 mg PO 12 hrly hypotension, worsening HF, edema, flushing,
May increase to 180-360 mg/day bradycardia, palpitations); GI effects (constipation,
PO divided 8 hrly dry mouth, digestive problems, N/V, diarrhea); CNS
Extended-release (once daily): effects (headache, dizziness); Other effects (fatigue,
rashes, hepatitis, transient elevation of liver
HYPERTENSION
Initial dose: 90-180 mg PO enzymes)

24 hrly
May increase dose at 14-day
intervals to 240-360 mg PO • Contraindicated in patients w/ sick sinus syndrome,
24 hrly 2nd- or 3rd-degree AV block, acute MI, pulmonary
congestion, hypotension
• Use w/ caution in patients w/ CHF, impaired hepatic/
Extended-release (twice daily): renal function, 1st-degree AV block, bradycardia
Dihydropyridines
Amlodipine2 Initial dose: 5 mg PO 24 hrly Adverse Reactions
Max dose: 10 mg/day • CV effects (depression of cardiac function,
Barnidipine Initial dose: 5-10 mg PO 24 hrly hypotension, worsening HF, edema, flushing,
bradycardia); GI effect (constipation); CNS effects
May be increased to 10-15 mg PO (headache, dizziness)
24 hrly
• Short-acting dihydropyridine agents should be
Benidipine Initial dose: 2-4 mg PO 24 hrly avoided because they have the potential to enhance
Max dose: 8 mg/day risk of adverse cardiac events
Cilnidipine Initial dose: 5-10 mg PO 24 hrly Special Instructions
Max dose: 20 mg/day • Contraindicated in patients w/ overt decompensated
Felodipine Initial dose: 2.5-5 mg PO 24 hrly Amlodipine, Felodipine) are tolerated in patients w/
Maintenance dose: 2.5-10 mg PO decreased LV ejection fraction
24 hrly
Max dose: 20 mg/day
Isradipine Regular release:
Initial dose: 2.5 mg PO 12 hrly
after 3-4 wk
Extended-release: 5 mg PO
24 hrly
1Combinations of calcium antagonist & ACE inhibitor; calcium antagonist & angiotensin II antagonist; calcium antagonist & beta-
blocker are available.
2Combinations of Amlodipine & Atorvastatin; Amlodipine & Hydrochlorothiazide; Amlodipine & Indapamide are available.

B180
Dosage Guidelines

Drug Dosage Remarks
Dihydropyridines (Cont'd)
Lacidipine Initial dose: 2 mg PO 24 hrly Adverse Reactions
May be increased to 4 mg, if necessary to 6 mg • CV effects (depression of cardiac
PO 24 hrly after at least 3-4 wk interval function, hypotension, worsening
HF, edema, flushing, bradycardia);
Lercanidipine Initial dose: 10 mg PO 24 hrly
GI effect (constipation); CNS effects
May increase to 20 mg PO 24 hrly after 2 wk (headache, dizziness)
Levamlodipine 2.5 mg PO 24 hrly • Levamlodipine: Tachycardia, cough,
HYPERTENSION
besilate May be increased up to 5 mg PO 24 hrly breathing difficulty, vertigo,
(S-amlodipine) headache, facial puffiness,
Manidipine Initial dose: 10 mg PO 24 hrly cheerlessness
Maintenance dose: 10-20 mg PO 24 hrly • Short-acting dihydropyridine agents
should be avoided because they have
Nicardipine Regular release: the potential to enhance risk of
Initial dose: 10-20 mg PO 8 hrly adverse cardiac events
May be increased to 20-40 mg PO 8 hrly Special Instructions
Extended-release: 40 mg PO 12 hrly • Contraindicated in patients w/ overt
May be increased to 80-120 mg PO 12 hrly decompensated HF, though
vasoselective dihydropyridines (eg
Nifedipine Regular release: Amlodipine, Felodipine) are
Initial dose: 5-10 mg PO 8 hrly tolerated in patients w/ decreased LV
May increase gradually to 30-80 mg 24 hrly over ejection fraction
7-14 days • Levamlodipine: Avoid concomitant
Max dose: 60-180 mg/day use w/ Isoprinoline & Dopamine
Extended-release (once daily):
Initial dose: 30 or 60 mg PO 24 hrly
May increase dose gradually at 7-14 days interval
Maintenance dose: 30-60 mg/day PO
Max dose: 90 mg/day
Extended-release (twice daily):
Maintenance dose: 20 mg PO 12 hrly
May increase stepwise to 40 mg 12 hrly
Max dose: 90 mg/day
Nisoldipine Immediate-Release:
May increase dose gradually at intervals of no less
than 1 wk
Modified-release:
May be increased by 8.5 mg/wk or longer
intervals
Nitrendipine 20 mg PO 24 hrly or 10 mg PO 12 hrly
May be increased to 20 mg PO 12 hrly
Max dose: 40 mg/day
1Combinations of calcium antagonist & ACE inhibitor; calcium antagonist & angiotensin II antagonist; calcium antagonist & beta-
blocker are available.

B181
Dosage Guidelines

Drug Dosage Remarks
Phenylalkylamines
Gallopamil 25-50 mg PO 6-12 hrly Adverse Reactions
Max dose: 200 mg/day • CV effects (depression of cardiac function, hypotension,
Verapamil Regular release: worsening HF, edema, flushing, bradycardia); GI effect
40-80 mg PO 6-8 hrly or (constipation); CNS effects (headache, dizziness)
80-160 mg PO 8-12 hrly • HR-modulating Ca antagonists (eg Diltiazem, Gallopamil
Max dose: 480 mg/day & Verapamil): AV dissociation, AV block, bradycardia &
HYPERTENSION
sinus node dysfunction

Extended-release:
May increase to 240 mg • Contraindicated in patients w/ overt decompensated HF,
PO 12 hrly though vasoselective dihydropyridines (eg Amlodipine,
Felodipine) are tolerated in patients w/ decreased LV
Max dose: 480 mg/day ejection fraction
patients w/ bradycardia, sinus node dysfunction & AV
nodal block
DIRECT RENIN INHIBITOR

Drug Dosage Remarks
Aliskiren2 Initial dose: 150 mg PO Adverse Reactions

24 hrly • GI effects (diarrhea, abdominal pain, dyspepsia, GERD);
If BP is not adequately CNS effects (headache, dizziness); Other effects
controlled, may increase (hypotension, rash, cough, hyperuricemia, fatigue, back
up to 300 mg PO 24 hrly pain, gout, renal calculi, hyperkalemia, dec in Hb levels,
Max dose: 300 mg/day seizures, angioedema)
• Contraindicated in patients w/ severe renal impairment or
renovascular hypertension, & in patients w/ a history of
angioedema (of any etiology)
• Concomitant use of Aliskiren w/ ACE inhibitors or
angiotensin II antagonists in diabetic patients is
contraindicated
• Avoid concomitant use of Aliskiren w/ ACE inhibitors or
angiotensin II antagonists in patients w/ moderate to
severe renal impairment (GFR <60 mL/min)
• Symptomatic hypotension may be seen in patients starting
Aliskiren therapy. Prior to initiation of treatment,
correction of hypovolemia &/or close monitoring of
volume status is warranted, especially in patients on
concurrent diuretics
• Contraindicated in pregnancy. Discontinue use once
pregnancy is detected
2Combinations of Aliskiren & Hydrochlorothiazide are available.

B182
Dosage Guidelines
DIURETICS
Drug Dosage Remarks
Eplerenone 50 mg PO 24 hrly Adverse Reactions
May increase up to • CNS effects (headache, dizziness); GI effects (diarrhea, nausea,
100 mg/day abdominal pain); Endocrine & metabolic effects (gynecomastia,
abnormal vaginal bleeding, hypercholesterolemia,
hypertriglyceridemia, hyperkalemia); Other effects (hypotension,
fatigue, influenza-like symptoms, renal function abnormality)
HYPERTENSION
• Avoid in patients w/ type 2 diabetes w/ microalbuminuria,
severe hepatic impairment; serum creatinine >2.0 mg/dL in
males or >1.8 mg/dL in females; creatinine clearance ≤50 mL/
min, serum potassium level >5.0 mmol/L
• Avoid concomitant use of K-sparing diuretics & K supplements
• Serum potassium should be measured before treatment &
1 mth after starting treatment
Spironolactone1 25-50 mg/day PO Adverse Reactions
May increase up to • CNS effects (headache, drowsiness, ataxia, mental confusion);
100 mg/day GI effects (cramps, diarrhea); Endocrine & metabolic effects
(gynecomastia, hirsutism, menstrual irregularities, impotence,
mild acidosis, hyponatremia, hyperkalemia & transient
increases in BUN)
• Avoid in patients w/ acute renal insufficiency, hyperkalemia or
severe renal impairment
• Use w/ caution in patients at increased risk of developing
hyperkalemia (eg DM, elderly, patients w/ renal or hepatic
impairment)
• Use w/ caution during concomitant use of other K-sparing
diuretics, ACE inhibitors, NSAIDs, ARBs, aldosterone
blockers, heparin & LMWH
• Serum electrolytes & BUN should be measured periodically
Loop Diuretics
Bumetanide 1 mg PO 24 hrly Adverse Reactions
Max dose: 4 mg/day • Endocrine & metabolic effects (hyponatremia, hypokalemia &
hypochloremic alkalosis especially after large doses or
prolonged administration, hyperglycemia, glycosuria,
hyperuricemia & may precipitate gout)
Furosemide 20-40 mg PO 12 hrly • Signs of electrolyte imbalances: Headache, muscle cramps, dry
usually in the mouth, hypotension, thirst, weakness, drowsiness, etc
morning • Less common effects (blurred vision, dizziness, orthostatic
hypotension, skin rashes & hypersensitivity reactions)
Piretanide 6-12 mg PO 24 hrly Special Instructions
Torasemide Initial dose: 2.5-5 mg • Avoid in patients w/ anuria or in renal insufficiency caused by
PO 24 hrly nephrotoxic or hepatotoxic drugs or caused by hepatic coma
Max dose: 5 mg/day • Use w/ caution in patients w/ existing or in those at risk of
fluid & electrolyte imbalances, in patients w/ prostatic
hyperplasia or impairment of micturition, patients w/ hepatic
cirrhosis are more likely to develop hypokalemia & patients w/
severe HF are more likely to suffer hyponatremia, use w/
caution in patients susceptible to gout
• Monitor patient for signs of fluid or electrolyte imbalance
1Combination w/ Hydroflumethiazide is available.

B183
Dosage Guidelines
Drug Dosage Remarks
Potassium-Sparing Diuretic
Amiloride 5-10 mg PO 24 hrly Adverse Reactions
Max dose: 20 mg/day • Endocrine & metabolic effects (hyperkalemia
especially in the elderly, patients w/ DM &
patients w/ impaired renal function,
hyponatremia has occurred in patients
receiving combination diuretic therapy);
GI effects (N/V, abdominal pain, diarrhea,
constipation, thirst); CNS effects (headache,
HYPERTENSION
dizziness, weakness, muscle cramps);

Dermatologic effects (rash, pruritus)
• Usually used in conjunction w/ loop or
thiazide diuretics
• Avoid in patients w/ hyperkalemia or severe
renal impairment
• Use w/ caution in patients at increased risk
of developing hyperkalemia (eg DM, elderly,
patients w/ renal or hepatic impairment)
Thiazides & Related Diuretics1
Chlorothiazide 500-1000 mg/day PO or divided Adverse Reactions
12 hrly • Endocrine & metabolic effects (hyperuricemia
Max dose: 2 g/day & may precipitate gout in some patients,
hypochloremic alkalosis, hyponatremia,
Chlortalidone 12.5-25 mg PO 24 hrly hypokalemia, hyponatremia,
(Chlorthalidone) May increase to 50 mg/day PO hypomagnesemia, hyperglycemia & glucosuria
in DM or other susceptible patients); GI effects
(GI irritation, N/V, constipation, anorexia,
Cyclopenthiazide 0.25-0.5 mg PO 24 hrly diarrhea); CNS effects (headache, dizziness);
Other effects (photosensitivity reactions,
postural hypotension, impotence,
Hydrochlorothiazide2 Initial dose: 12.5 mg PO 24 hrly hypersensitivity reactions)
(Dihydrochlorothiazide) Usual dose: 25-100 mg 24 hrly • Signs of electrolyte imbalances: Headache,
muscle cramps, dry mouth, hypotension,
Indapamide Regular release: thirst, weakness, drowsiness, etc
2.5 mg PO 24 hrly Special Instructions
Extended-release: 1.5 mg PO • Avoid in patients w/ severe hepatic impairment
24 hrly since encephalopathy may be precipitated; in
patients w/ severe renal impairment, anuria
Metolazone Initial dose: 1.25 mg PO 24 hrly or preexisting hypercalcemia
Usual dose: 2.5-5 mg PO 24 hrly • Use w/ caution in patients w/ existing or at
risk of fluid & electrolyte imbalances (eg
Enhanced bioavailability elderly), patients w/ hepatic cirrhosis are
formulas: 0.5-1 mg PO 24 hrly more likely to develop hypokalemia &
patients w/ severe heart failure are more
Trichlormethiazide 1-4 mg PO 24 hrly likely to suffer hyponatremia, use w/ caution
in patients w/ renal impairment, in patients
Tripamide 15 mg PO 12-24 hrly susceptible to gout & in DM patients
• Monitor patient for signs of fluid or
electrolyte imbalance
1Combinations of thiazide diuretic & ACE inhibitor; thiazide diuretic & angiotensin II antagonist; thiazide diuretic & beta-blocker
are available.
2Combinations of Hydrochlorothiazide & Amiloride; Hydrochlorothiazide & Triamterene are available.

B184
Dosage Guidelines
OTHER ANTIHYPERTENSIVES
Drug Dosage Remarks
Centrally Acting Agents
Clonidine Initial dose: Adverse Reactions
50-100 mcg PO 8 hrly or • CNS effects (drowsiness, dizziness, headache, depression,
75-150 mcg PO 12 hrly anxiety, fatigue, sleep disturbances, impotence); GI effects
Maintenance dose: (dry mouth, constipation, nausea, anorexia); GU effects
(urinary retention, incontinence); CV effects (orthostatic
300-1200 mcg/day PO in hypotension, fluid retention)
divided doses
HYPERTENSION
• Less common effects: Bradycardia, ECG disturbances,
Max dose: heart failure, hallucinations, etc
2.4 mg/day Special Instructions
• Use w/ caution in patients w/ cerebrovascular disease, renal
impairment, ischemic heart disease, MI, occlusive
peripheral vascular disorders or in those w/ history of
depression
abruptly
Methyldopa Initial dose: Adverse Reactions
250 mg PO 8-12 hrly • Most adverse effects are transient or reversible
May increase or decrease • CNS effects (drowsiness, dizziness, lightheadedness,
dose not more frequently headache, weakness, fatigue, impotence, disturbed sleep,
than 2-day intervals until paresthesia, depression, etc); CV effects (postural
desired effect is achieved hypotension, fluid retention, edema & may aggravate
Maintenance dose: angina); GI effects (N/V, diarrhea, constipation, rarely
500-2000 mg in 2-4 divided pancreatitis, colitis or sore tongue); Hematologic effects
doses (thrombocytopenia, leukopenia, hemolytic anemia &
Max dose: granulocytopenia have occurred); Hypersensitivity reactions
3 g/day Special Instructions
• Avoid in patients w/ liver disease or depression
• Use w/ caution in patients w/ impaired renal or hepatic
function, history of hemolytic anemia, liver disease or
depression & in patients w/ parkinsonism
• CBC should be measured periodically during the 1st
6-12 wk of therapy or if patient develops unexplained fever
Moxonidine Initial dose: Adverse Reactions
0.2 mg PO 24 hrly • Similar to Clonidine but less sedation & dry mouth
May increase after 3 wk to Special Instructions
0.4 mg/day PO or divided • Avoid in patients w/ conduction disorders, severe arrhythmias,
12 hrly bradycardia, severe HF, severe ischemic heart disease, severe
Max dose: renal or hepatic impairment, intermittent claudication or
0.6 mg/day in 2 divided Raynaud’s disease, Parkinson’s disease, epilepsy, glaucoma or
doses depression & in patients w/ history of angioedema
abruptly
Rilmenidine Initial dose: Adverse Reactions
1 mg PO 24 hrly • Similar to Clonidine but less sedation & central effects
May increase after 1 mth Special Instructions
to 1 mg PO 12 hrly • Similar to Clonidine

B185
Dosage Guidelines
OTHER ANTIHYPERTENSIVES (CONT’D)

Drug Dosage Remarks
Direct Vasodilators
Hydralazine Initial dose: Adverse Reactions
40-50 mg/day PO • Typically subside w/ continued therapy: CV effects (tachycardia,
in divided doses palpitations, angina, flushing); GI effects (anorexia, N/V, diarrhea);
May increase by Other effects (dizziness, nasal congestion)
10-25 mg/dose • Other CV effects (postural hypotension, fluid retention, edema); Other
every 2-5 days effects (wt gain, tremor, conjunctivitis, muscle cramps, lacrimation)
Max dose: • Less common: Pyridoxine depletion resulting in peripheral
200 mg/day neuropathy; Hematologic effects (blood dyscrasia, hemolytic
HYPERTENSION
anemia); Hepatic effect (hepatotoxicity); Genitourinary effects

(difficulty in urinating, glomerulonephritis); CNS effects
(depression, anxiety); GI effects (paralytic ileus, constipation);
Hypersensitivity reactions; can also cause a condition resembling
SLE when prolonged high doses are used & is more common in
women & in patients w/ renal impairment
• Avoid in patients w/ severe tachycardia, HF w/ high cardiac output,
dissecting aortic aneurysm, cor pulmonale or myocardial insufficiency
due to mechanical obstruction, idiopathic SLE & related disorders
• Use w/ caution in patients w/ ischemic heart disease, recent MI,
heart failure, impaired renal or hepatic function
• CBC, antinuclear antibody determinations & urinalysis should be
done periodically during long-term therapy
Minoxidil Initial dose: • Indicated only for severe hypertension that has not responded to
5 mg/day PO or in other antihypertensive therapy
divided doses • Minoxidil is usually given in combination w/ a beta-blocker to diminish
May increase dose cardiac-accelerating effects & w/ a diuretic to control edema
gradually at 3-day Adverse Reactions
intervals to 40 mg/ • CV effects (reflex tachycardia, fluid retention, edema, deterioration
day PO or in of existing heart failure, ECG changes, pericarditis w/ effusion,
divided doses pericarditis, angina); hypertrichosis
Max dose: • Less common: CNS effect (headache); Endocrine & metabolic
100 mg/day effects (gynecomastia, polymenorrhea); Other effects (nausea;
allergic skin rashes, Stevens-Johnson syndrome, thrombocytopenia)
• Avoid in patients w/ pheochromocytoma
• Use w/ caution in patients w/ recent MI, pulmonary hypertension,
angina, CHF & significant renal impairment
Peripherally Acting Agent
Reserpine1 Initial dose: Adverse Reactions
0.5 mg/day PO in • CNS effects (headache, depression, drowsiness, dizziness, lethargy,
divided doses x 2 wk nightmares); Resp effect (nasal congestion); GI effects (increased GI
Then reduce to: motility eg diarrhea, abdominal cramps & increased gastric acid
Maintenance dose: secretion & less commonly: Appetite changes, wt gain, dry mouth);
0.1-0.25 mg/day PO CV effects (bradycardia, hypotension)
Max dose: • Less common effects: Galactorrhea, increased prolactin concentration,
0.5 mg/day impotence, Na retention, edema, rash, thrombocytopenic purpura
• Avoid in patients w/ pheochromocytoma, Parkinson's disease,
active peptic ulcer or ulcerative colitis, history of mental depression
• Use w/ caution in patients w/ arrhythmias, MI, renal impairment,
gallstones, epilepsy, allergic bronchial asthma & elderly
1Combination w/ Clopamide & Dihydroergocristine mesylate is available.

B186
Dosage Guidelines
OTHER ANTIHYPERTENSIVES (CONT’D)

Drug Dosage Remarks
Other Combinations
Reserpine/ Reserpine 0.1 mg/ Adverse Reactions
Hydralazine/ Hydralazine 25 mg/ • GI effects (diarrhea, GI disorder); CV effects (bradycardia,
Hydrochlorothiazide Hydrochlorothiazide palpitations, arrhythmias, orthostatic hypotension);
15 mg Metabolic effects (hypokalemia, hyperuricemia, impaired
1 tab PO 8 hrly glucose metabolism); Other effects (nasal congestion,
depression, lightheadedness, muscle weakness, dizziness,
cramps, rash, fatigue, paresthesia)
HYPERTENSION
• Avoid in patients w/ history of depression, active peptic
ulcer, ulcerative colitis, parkinsonism,
pheochromocytoma, anuria, renal decompensation,
patients recently treated w/ MAOIs, patients under
lithium therapy
• Use w/ caution in anesth; patients w/ coronary &/or
cerebral arteriosclerosis, electroshock therapy, electrolyte
imbalance, hepatic or renal impairment
PERIPHERAL VASODILATORS & CEREBRAL ACTIVATORS

Drug Dosage Remarks
Co-dergocrine 1-2 mg PO 8 hrly Adverse Reactions
mesylate • CNS effect (headache); Other effects (GI upset, blurred
(Dihydroergocryptine, vision, skin rash, nasal stuffiness)
Dihydroergocristine & Special Instructions
Dihydroergocornine
mesylates) • Should be taken w/ food
• Use w/ caution in patients w/ severe bradycardia
Nicergoline Adjuvant therapy: Adverse Reactions
5-10 mg PO 8 hrly • CNS effects (dizziness, drowsiness, insomnia); Other
or effects (slight GI disturbances, sensation of heat &
30 mg PO 12 hrly cutaneous flushing, hypotension)
• Use w/ caution in patients w/ hyperuricemia or those w/
history of gout &/or in treatment w/ drugs that interfere
w/ the metabolism & excretion of uric acid

B187
Ischemic Stroke (1 of 18)
1
Patient presents w/ signs & symptoms suggestive of acute stroke
IMMEDIATE MANAGEMENT
• Assess & stabilize airway, breathing & circulation (ABC)
• Assess for hypoglycemia & electrolyte imbalance1
• Obtain IV access, administer fluids2 as needed
• ECG
• Non-contrast CT scan of the brain or cranial MRI w/ DWI
2 3
DIAGNOSIS No ALTERNATIVE
Is ischemic stroke DIAGNOSIS
confirmed?
Yes
B BP management
(Pre-thrombolytic A BP management
therapy) 4 (Non-rt-PA
SBP >185 mmHg or
EVALUATION patients)
DBP >110 mmHg
Is patient eligible for SBP ≥220 mmHg or
• Labetalol IV Yes No DBP >120 mmHg
recombinant tissue
• Nicardipine IV plasminogen activator • Captopril PO
If BP is not (rt-PA)? • Labetalol IV
reduced & remains
• Nicardipine IV
>185/110 mmHg,
DO NOT GIVE rt-PA
ADMIT TO STROKE UNIT

OR ICU
C Thrombolysis
• Obtain consent
from patient &
family E Other therapeutic measures
D Peri-/Post-
F Supportive care & rehabilitation
thrombolysis
BP management
G Secondary prevention
1Hypoglycemia & electrolyte imbalance may have neurologic manifestations of focal & general symptoms, altered speech &/or cognitive
changes.
2Dextrose-containing fluids should be avoided unless patient is hypoglycemic.
B188
1 STROKE
• Stroke or cerebrovascular disease is defined as a sudden onset of focal neurological deficit or any alteration in
level of consciousness due to an underlying vascular pathology
- Brain involvement is evident clinically or as documented in imaging studies based on the onset of
symptoms
• Ischemic stroke is a type of stroke characterized by the sudden absence of blood supply to an area of the brain,
spinal cord or retina secondary to a thrombus, emboli, or intracranial small vessel disease
• Most common risk factors include hypertension & diabetes mellitus (DM)
• Rapid evaluation is essential for use of time-sensitive treatments & to prevent further brain damage
Common Presentation of Patients w/ Acute Ischemic Stroke
Left (dominant) Hemisphere
• Left gaze preference
• Right visual field deficit
• Right hemiparesis
• Right hemisensory loss
• Dysarthria
• Aphasia (Broca’s, Wernicke’s, Global)
• Apraxia
• Visual agnosia
Right (non-dominant) Hemisphere
• Right gaze preference
• Left visual field deficit
• Left hemiparesis
• Left hemisensory loss (hemi-inattention)
• Neglect of left side
• Dysarthria
ISCHEMIC STROKE
Brainstem
• Nausea/vomiting (N/V)
• Diplopia, dysconjugate gaze, gaze palsy, nystagmus
• Dysarthria, dysphagia
• Vertigo, syncope
• Hemiparesis or quadriplegia
• Sensory loss in hemibody or all 4 limbs
• Decreased consciousness
• Hiccups, abnormal respirations
• Alexia or inability to understand words written
Cerebellum
• Truncal/gait ataxia, limb ataxia
• Dysarthria
• Vertigo, nystagmus
2 DIAGNOSIS
• Determine if patient’s symptoms are due to stroke, identify other conditions requiring immediate intervention
& determine the potential causes of stroke
History & Physical Exam
• Time of symptom onset is the single most important piece of historical information
- Stroke onset defined as the last time patient was symptom-free
• Obtain circumstances around the development of symptoms & features that may point to other potential
causes of symptoms
• Identify risk factors for arteriosclerosis & cardiovascular disease; medications, conditions that may predispose
to bleeding complications; history of drug abuse, infection, migraine, seizure, trauma, oral contraceptive use
or pregnancy
• Complete physical examination including vital signs, oxygen saturation & body temperature
• Brief but thorough neurologic exam
B189
2 DIAGNOSIS (CONT'D)
History & Physical Exam (Cont'd)
Clinical Stroke Score
• National Institutes of Health Stroke Scale (NIHSS)
- Helps quantify the degree or severity of neurological deficit & may identify possible location of lesion/
occlusion
- Facilitates communication between healthcare professionals & may provide prognostic information
- May identify patients eligible for interventions & potential risk for complications
Neuroimaging Studies
• Should be done on all admitted patients suspected of acute stroke
• Performed within 20 minutes of arrival in the emergency room for patients who may be candidates for IV
Alteplase &/or mechanical thrombectomy
Non-contrast Cranial Computed Tomography (NCCT)
• Differentiates ischemic from hemorrhagic stroke or other structural brain lesions that may mimic stroke
• CT scan may be normal within 1st 24 hours of ischemia but will show hemorrhages from onset of hemorrhagic
stroke
• Mandatory before initiating any specific therapy to treat acute ischemic stroke
• Effective in ruling out intracerebral hemorrhage (ICH) prior to IV Alteplase administration
• Alberta Stroke Program Early Computed Tomography Score (ASPECTS) helps in the detection of early ischemic
changes & should be evaluated in patients who are candidates for IV thrombolysis
• Hyperdense middle cerebral artery (MCA) CT should not be used as criteria to withhold IV Alteplase
Cranial Computed Tomography Angiography (CTA)
• May be used on patients suspected w/ intracranial large vessel occlusion without renal impairment history &
is a candidate for thrombectomy
- For patients on Metformin, postponement of administration of Metformin should be considered
• Serum creatinine concentration may be deferred if patient does not present w/ renal impairment
ISCHEMIC STROKE
Magnetic Resonance Imaging (MRI) of the Brain

• MRI is more sensitive & specific for diagnosis of ischemic stroke & determination of the extent of reversible
or irreversible cerebral ischemia especially for stroke within 3-8 hours
• Important in patients w/ unusual presentations, silent cerebrovascular disease especially chronic microbleeds,
rare stroke varieties, or in whom stroke mimics are suspected but not clarified on CT
• May be used to rule out ICH prior to IV Alteplase administration
• Can be used to identify diffusion-positive fluid-attenuated inversion recovery (FLAIR)-negative lesions that
can be a basis in selecting patients who can benefit from rt-PA administration after 4.5 hours of stroke symptom
recognition
• It is not recommended to use MRI to exclude cerebral microbleeds before IV Alteplase administration
Cranial MRI w/ Diffusion-Weighted Imaging (DWI)
• Highly sensitive in detecting early cerebral ischemic changes in acute stroke patients
Vascular Imaging
• CT & MR angiography, transcranial Doppler ultrasonography, carotid duplex sonography & catheter angiography
have been used to detect intracranial or extracranial vessel abnormalities
Diagnostic Tests
• Blood glucose, complete blood count (CBC) w/ platelet count, renal function test, serum electrolytes,
prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT),
D-dimer, fibrinogen
• Cardiac biomarkers may be done to confirm or rule out acute coronary syndrome if needed
• 12-lead electrocardiogram (ECG)
• Chest X-ray
Perform the following tests, if required:
• Toxicology screen, blood alcohol level
• Arterial blood gas (if hypoxia is suspected)
• Liver function tests
• Pregnancy test
• Lumbar puncture (if subarachnoid hemorrhage is suspected & CT is negative for blood)
• Electroencephalography (EEG) (if seizures are suspected)
• Echocardiogram (if cardioembolism is suspected)
B190
• Exclude stroke mimics or conditions w/ stroke-like symptoms that include migraine, hypertensive encephalopathy,
hypoglycemia, seizures or post-ictal paresis
Bell’s Palsy
Benign Paroxysmal Positional Vertigo (BPPV)
Cerebral Venous Sinus Thrombosis
• Patients may experience depressed consciousness, generalized headaches, generalized psychiatric disorder (eg
depression), nausea, paresis, seizures, visual disturbances, vomiting
• 3rd cranial nerve palsy, papilledema, proptosis may be observed
• High-risk patients include those who have dehydration, drugs (eg androgen, methylenedioxymethamphetamine
(MDMA), oral contraceptives), low-flow states, hypercoagulable states, infectious process, pregnancy or
postpartum state, trauma, & venous sinus compression
Collagen Vascular Diseases (eg lupus, polyarteritis nodosa)
Demyelinating Diseases
Epidural or Subdural Hematoma
• Presents w/ focal neurologic signs, mental status alteration which may rapidly progress to coma
• Commonly seen in elderly patients prone to recurrent falls leading to chronic subdural hematomas
Giant Cell Arteritis
• Seen in older adults presenting w/ claudication of the jaw, intermittent fever, malaise, morning stiffness, myalgia,
severe headache, visual disturbance & rarely aphasia & hemiparesis
Hypertensive Encephalopathy
• Presents w/ significant hypertension, headache, delirium & cerebral edema
Intracerebral Hemorrhage (ICH)
• Please see Intracerebral Hemorrhage disease management chart for further information
Intracranial Mass
• Eg tumor, abscess
ISCHEMIC STROKE
• Differentiated by CT scan or MRI scan; defined by gradual onset of symptoms; may present w/ stroke-like
deterioration
Labyrinthitis
Metabolic Disorders, Metabolic Encephalopathy
• Hypo- & hyperglycemia may present w/ stroke-like symptoms
Ménière's Disease
• Presents as dizziness, hearing loss, tinnitus & vertigo w/ or without verbal, visual or other focal symptoms
Migraine
• Neurologic symptoms usually have a gradual onset; migrainous aura may be confused w/ stroke or transient
ischemic attack (TIA)
Neuroses
Peripheral Nerve Disorders
• Present w/ a specific pattern of distribution of symptoms
Seizure
• Post-seizure patients can present w/ unilateral weakness (Todd’s paralysis)
• Neurologic symptoms are usually positive rather than losing function
Syncope & Transient Global Amnesia
Transient Ischemic Attack (TIA)
B191
4 EVALUATION
Intravenous rt-PA should only be administered under the following conditions:
• Physician & staff w/ expertise in acute stroke management, in delivering thrombolysis & in monitoring for
complications
• Immediate access to high-resolution imaging (eg noncontrast CT scan) facilities which are available 24 hours/
day & staff trained & experienced in interpreting the results
• Facility has the means to treat potential complications (eg ICH)
• Intravenous rt-PA is given only to patients satisfying specific inclusion & exclusion criteria
Patient Inclusion Criteria
• Patients within 3-4.5 hours of acute ischemic stroke symptom onset or last known well or baseline state
• Ischemic stroke w/ measurable neurological deficit by clinical assessment confirmed through neuroimaging
& shows no signs of hemorrhage
• Medically eligible patients ≥18 years of age
• In the 3- to 4.5-hour window, patients ≤80 years old w/ no known history of both diabetes mellitus & stroke,
NIHSS score ≤25, not taking any oral anticoagulants & no evidence of ischemic injury involving >⅓ of the
MCA territory on imaging
- May be given w/ caution in patients >80 years of age presenting in the 3-to 4.5-hour window from stroke
onset
• Mild w/ disabling stroke symptoms to severe stroke symptoms
• Known case of sickle cell disease presenting w/ acute ischemic stroke
• Patients w/ blood pressures (BP) that can be lowered safely to <185/110 mmHg w/ antihypertensive agents
• Patients w/ history of small number (1-10) of cerebral microbleeds demonstrated on MRI
• Initial glucose levels >50 mg/dL
Patient Exclusion Criteria
Clinical Contraindications
• Onset of stroke >4.5 hours prior to planned start of treatment
ISCHEMIC STROKE
• Neurologic deficit is minor or spontaneously & rapidly improving

• Symptoms of stroke suggestive of subarachnoid hemorrhage, regardless of CT result
• Hypertension: Systolic BP (SBP) >185 mmHg & diastolic BP (DBP) >110 mmHg on repeated measurements
despite aggressive treatment to lower BP
• In the setting of MCA stroke, an obtunded or comatose state may be a relative contraindication
• Signs of active internal bleeding or acute trauma (ie fracture) on examination
• Mild nondisabling stroke symptoms (NIHSS score 0-5) that can be treated within 3 & 4.5 hours of ischemic
stroke symptom onset or last known well or baseline state
History Contraindications
• Major surgery (eg recent intracranial or spinal surgery) within 3 months or serious trauma within the last
2 weeks
• History of or current intracranial hemorrhage
• Prior stroke or serious head injury in the preceding 3 months
• Gastrointestinal or urinary tract hemorrhage within 21 days
• Structural gastrointestinal malignancy
• Infective endocarditis
• Arterial puncture at a noncompressible site within the preceding 7 days or lumbar puncture within the last
3 days
• Untreated cerebral aneurysm, arteriovenous malformation (AVM) or brain tumor
• Clinical presentation suggestive of post-myocardial infarction (MI) pericarditis
• Patient is taking oral anticoagulants (eg Warfarin) & w/ INR >1.7 or PT >15 seconds
• Direct thrombin inhibitors or direct factor Xa inhibitors
- May be re-evaluated if lab tests (eg aPTT, INR, platelet count) are normal or if last dose of these agents was
taken >48 hours in patients w/ normal renal function
• Patient has received heparin within the last 48 hours & has an elevated aPTT greater than the upper limit of
normal
• Patient has received low-molecular-weight heparin (LMWH) within the last 24 hours
• Known hereditary or acquired hemorrhagic diathesis or unsupported coagulation factor deficiency
• Known case or suspected case of aortic arch dissection
B192
Patient Exclusion Criteria (Cont'd)
Laboratory Contraindications
• Platelet count <100,000 mm3
• INR >1.7 & elevated aPTT (>1.5x normal)
• Positive pregnancy test
Radiology Contraindications
• Intracranial hemorrhage
• Large area of low attenuation consistent w/ an infarcted brain (time of symptom onset may have been earlier)
• Intracranial tumor, aneurysm, AVM or other space-occupying lesion
Relative Exclusion Criteria
• Seizure at stroke onset
• Pregnancy or possible pregnancy
• >10 cerebral microbleeds on MRI
• Acute MI occurred in the past 3 months is a ST-elevation myocardial infarction (STEMI) involving the left
anterior myocardium
• History of gastrointestinal or genitourinary bleeding
BLOOD PRESSURE MANAGEMENT

• Elevated BP is a major risk factor for both 1st & subsequent stroke
• Both elevated & low BPs are associated w/ poor outcome in acute ischemic stroke
• Mild & moderately elevated BP should not be routinely lowered in the acute phase of stroke as this may worsen
outcome
- Avoid aggressive BP lowering as this is detrimental in acute stroke
ISCHEMIC STROKE
• Hypotension & hypovolemia should be corrected in order to maintain systemic perfusion levels that are essential
to organ function
• Elevated BP in stroke may be due to stress of cerebrovascular event, full bladder, nausea, pain, preexisting
hypertension, physiological response to increased intracranial pressure or to hypoxia
• Elevated BP usually resolves spontaneously within the 1st few days after a stroke
• Excessively high BP is lowered to decrease brain edema formation, reduce risk of hemorrhagic transformation
of the infarct, prevent further vascular damage & preclude early recurrent stroke
A BP MANAGEMENT (NON-rt-PA PATIENTS)

• Benefit of initiating or re-initiating antihypertensive treatment within the 1st 48-72 hours is not certain in
patients w/ SBP ≥220 mmHg or DBP ≥120 mmHg or MAP >130, without comorbid conditions requiring urgent
antihypertensive therapy & did not receive rt-PA or mechanical thrombectomy
• Starting or restarting antihypertensive medications during hospitalization in neurologically stable patients w/
BP of >140/90 mmHg is recommended to improve long-term BP control unless otherwise indicated
• In patients w/ markedly elevated BP, lower BP by 10-15% during the first 24 hours after onset of stroke
BP (mmHg) Treatment
SBP ≥220 mmHg or Labetalol: 10-20 mg IV over 1-2 minutes
DBP 121-140 mmHg May repeat or double the dose every 10 minutes
Max dose: 300 mg in 24 hours
or
Nicardipine: Initially, 5 mg/hr IV infusion; titrate to desired effect by increasing
2.5 mg/hr every 5 minutes
Max dose: 15 mg/hr
(Aim for 10-15% decrease in BP)
or
Captopril: 6.25-12.5 mg PO
B193
B BP MANAGEMENT (PRE-THROMBOLYTIC THERAPY)

• BP management of patients eligible for thrombolysis is critical before & during the administration of rt-PA & during
the ensuing 24 hours because severely elevated BP is associated w/ parenchymal hemorrhage
• Thrombolysis is not performed in patients w/ SBP >185 mmHg or DBP >110 mmHg at the time of treatment
• Correct BP using the following:
BP (mmHg) Treatment
SBP >185 mmHg or Labetalol: 10-20 mg IV over 1-2 minutes; may repeat once
DBP >110 mmHg or
Nicardipine: 5 mg/hr IV infusion; titrate up to desired effect by 2.5 mg/hr at
5- to 15-minute intervals
Max dose: 15 mg/hr
When desired BP is attained, adjust to maintain proper BP level
or
Clevidipine: 1-2 mg/hr IV, titrate by doubling the dose every 2-5 minutes until
desired BP is reached
Max dose: 21 mg/hr
or
Other agents (eg Hydralazine, Enalapril)
• If BP is not reduced & remains >185/110 mmHg despite treatment, DO NOT GIVE rt-PA
• If medications are given to lower BP, maintain the BP level below 180/105 mmHg for at least the first 24 hours
after IV rt-PA treatment
C THROMBOLYSIS
Intravenous Thrombolysis w/ Recombinant Tissue Plasminogen Activator (rt-PA)
• rt-PA (Alteplase) is the only thrombolytic proven effective in the treatment of acute ischemic stroke to be
administered ideally within 60 minutes of arrival of qualified patients
ISCHEMIC STROKE
• Patients eligible for rt-PA should be treated as quickly as possible within the time window as the benefits of
rt-PA diminish rapidly over time
• Carefully selected patients may have improved outcomes if treated within extended window of 3 to 4.5 hours
of stroke symptom onset
• Administering within 4.5 hours of stroke symptom recognition may be beneficial in patients w/ acute ischemic
stroke who awoke w/ stroke symptoms or have unclear time of onset >4.5 hours from last known well or at
baseline state & who have MRI DWI-FLAIR mismatch (DW-MRI lesion smaller than ⅓ of the MCA territory
& no visible signal change on FLAIR)
• May be beneficial in patients w/ acute ischemic stroke who had wake-up stroke, who had CT or MRI core/
perfusion mismatch within 9 hours from the midpoint of sleep & whom mechanical thrombectomy is neither
indicated nor planned
• Intracranial hemorrhage can occur w/ use; risk can be reduced by careful selection of patients & presence of
competent ancillary care
- Signs & symptoms of intracranial hemorrhage following rt-PA include new headache, acute neurological
deterioration, acute hypertension, nausea, or vomiting
- Should intracranial hemorrhage be suspected, discontinue rt-PA & do immediate non-contrast CT scan or
other neuroimaging tests to detect hemorrhage
• Angioedema is also a potential side effect which may cause partial airway obstruction
• Measure BP & assess neurological status every 15 minutes during & after IV rt-PA infusion for 2 hours, then
every 30 minutes for 6 hours, then hourly until 24 hours after IV rt-PA treatment
- BP of <180/105 mmHg should be maintained for at least 24 hours after IV rt-PA
• Obtain follow-up CT or MRI at 24 hours after IV rt-PA before starting anticoagulants or antiplatelet agents
• Should be administered w/ or without multimodal CT, MRI & perfusion imaging
• Should be administered if patient is eligible even if mechanical thrombectomy is being considered
Endovascular Interventions
• Criteria for endovascular therapy w/ a stent retriever or mechanical clot aspiration devices (all should be
present):
- A mRS score 0 to 1 prior to stroke
- Causative occlusion of the internal carotid artery or proximal MCA
- Age ≥18 years
- NIHSS score of ≥6
- Alberta Stroke Program Early CT score (ASPECTS) of ≥6
- Treatment can be initiated (groin puncture) within 6 hours of symptom onset
• Reduced time from symptom onset to reperfusion w/ endovascular therapies produces better clinical outcomes
- Reperfusion to TICI grade 2b/3 should be achieved as early as possible & within 6 hours of stroke onset
- It is not required to observe patients after IV rt-PA to assess for clinical response before pursuing endovascular
therapy to achieve beneficial outcomes
B194
C THROMBOLYSIS (CONT'D)
Endovascular Interventions (Cont'd)
• Endovascular therapy w/ intracranial thrombectomy may be considered in patients w/ anterior circulation
occlusion who have contraindications for IV rt-PA if it can be completed within 6 hours of stroke symptom onset
- May also be considered in patients <18 years w/ large vessel occlusion who can tolerate a groin puncture
within 6 hours of stroke symptom onset
Other Options
• Mechanical or Endovascular Thrombectomy
- Mechanical thrombectomy is recommended in patients w/ acute ischemic stroke within 6-16 hours of last
known normal who have large vessel occlusion in the anterior circulation & meet other DAWN or DEFUSE
3 eligibility criteria or acute ischemic stroke within 16-24 hours of last known normal who have large vessel
occlusion in the anterior circulation & meet other DAWN eligibility criteria
- Mechanical thrombectomy in posterior circulation stroke shows lower risk of symptomatic intracranial
hemorrhage & benefits when started beyond 6 hours after symptom onset
- Endovascular thrombectomy may be considered as treatment in eligible patients w/ acute basilar artery
occlusion despite lack of a published randomized controlled trial to date
- Studies have shown that endovascular thrombectomy within an extended time window (up to 24 hours) was
beneficial in some selected patients
- BP should be maintained at <180/105 mmHg during & 24 hours after the procedure
• Intra-arterial Thrombolysis
- Beneficial for patients w/ major ischemic strokes of <6 hours duration due to MCA occlusion
• Intravenous Fibrinolytics
- Tenecteplase may be used as an alternative to rt-PA in patients without contraindications to IV fibrinolysis
who are eligible to undergo mechanical thrombectomy
- May be considered as an alternative to rt-PA in patients w/ minor neurological deficit & no major intracranial
occlusion
- IV defibrinogenating agents or IV fibrinolytic agents other than Alteplase & Tenecteplase is not recommended
D TREATMENT OF ELEVATED BP DURING & AFTER rt-PA ADMINISTRATION
ISCHEMIC STROKE
• Monitor BP every 15 minutes for 2 hours from the start of rt-PA therapy, then every 30 minutes for 6 hours,
then every hour for the next 16 hours
BP (mmHg) Treatment
SBP >180-230 mmHg Labetalol: 5-10 mg IV followed by continuous IV infusion at 2-8 mg/min
or DBP >105-120 Max dose: 300 mg IV bolus
mmHg or
Nicardipine: 5 mg/hr IV infusion initially, then titrate to desired effect by 2.5 mg/
hr every 5-15 minutes
Max dose: 15 mg/hr
or
Clevidipine: 1-2 mg/hr IV then titrate by doubling the dose every 2-5 minutes
until desired BP
Max dose: 21 mg/hr
or
Nitroprusside: 0.5 mcg/kg/min IV infusion
Max dose: 8 mcg/kg/min
SBP >230 mmHg or Labetalol: 10-20 mg IV over 2 minutes; may repeat every 10-20 minutes
DBP 121-140 mmHg Max dose: 300 mg in 24 hours
or
Labetalol: 10 mg IV followed by continuous IV infusion at 2-8 mg/min
Max dose: 300 mg in 24 hours
or
Nicardipine: 5 mg/hr IV infusion initially, then titrate to desired effect by 2.5 mg/
hr every 5-15 minutes
Max dose: 15 mg/hr
or
Clevidipine: 1-2 mg/hr IV then titrate by doubling the dose every 2-5 minutes
until desired BP
Max dose: 21 mg/hr
• If BP is not controlled or DBP >140 mmHg, consider Sodium nitroprusside infusion at 0.5 mcg/kg/min (max
dose: 10 mcg/kg/min)
• If medications are given to lower BP, maintain the BP level below 180/105 mmHg for at least the first 24 hours
after IV rt-PA treatment
B195
E OTHER THERAPEUTIC MEASURES

Antiplatelet Agents
Aspirin
• Administered at a dose of 160-325 mg PO to most stroke patients & those who are not candidates for rt-PA
within 24-48 hours of stroke onset to prevent early recurrence, mortality & morbidity
- For patients treated w/ rt-PA, Aspirin should not be given within 24 hours after the start of rt-PA therapy,
though might be considered if w/ concomitant conditions for which such treatment given without rt-PA is
known to provide significant benefit or not giving such treatment is known to result in significant risk
- Contraindicated in patients w/ Aspirin allergy or suffering from gastrointestinal bleeding
• 21 days of dual antiplatelet therapy w/ Clopidogrel in minor stroke begun within 24 hours can be beneficial
for early secondary stroke prevention for up to 90 days from onset of symptoms
• Should not be used as a substitute if patient qualifies for other acute interventions (eg rt-PA)
Anticoagulant Agents
Heparins
• Eg Unfractionated heparin (UFH), LMWH & heparinoids
• Routine anticoagulation is not recommended
• Should not be used in lieu of rt-PA for treatment of otherwise eligible patients
• Administration within 24 hours of rt-PA is not recommended due to increased risk of bleeding complications
• SC UFH & LMWH may be considered for deep venous thrombosis (DVT) prophylaxis in at-risk patients
- Non-pharmacologic treatments for DVT prevention may also be used
- Risk vs benefit of pharmacologic agents needs to be considered
• Not shown to decrease mortality & morbidity nor prevent stroke recurrence
Intracranial Pressure Decompression
• Hyperventilation is an emergency measure which can decrease intracranial pressure by 25-30% when PCO2
is decreased by 5-10 mmHg
• Mannitol can be administered at a dose of 0.25-0.5 g/kg IV over 20 minutes every 6 hours
• Intra-ventricular catheter CSF drainage is usually done if there is presence of hydrocephalus
• Surgical decompression & hemicraniectomy within 48 hours after onset of symptoms may benefit patients
ISCHEMIC STROKE
≥60 years old w/ very large infarcts to prevent brain herniation

- May be considered in selected patients >60 years old
• Ventriculostomy & sub-occipital craniectomy may be done for patients w/ large cerebellar infarcts
Seizure
• The use of prophylactic anti-seizures or long-term anticonvulsant agents is not recommended in patients w/
1 self-limiting seizure episode happening at the onset or within 24 hours post-stroke
• New-onset seizures in hospitalized patients w/ acute stroke are treated w/ short-acting anti-seizure medications
if episodes are not self-limiting
• Monitor patients w/ immediate post-stroke seizure for recurrent seizure activity & treat per seizure guideline
recommendations
F SUPPORTIVE CARE & REHABILITATION

General Care
• Vital signs & neurological status should be monitored frequently during 1st 24-72 hours
• Bed rest followed by mobilization as soon as patient’s condition is stable
- Close observation is necessary during transition from sitting to standing; patient may experience a worsening
in neurological status upon movement to the upright position
- Early mobilization reduces risk of major complications (eg pneumonia, DVT, etc)
• During the 1st 24 hours, passive- & full-range motion exercises may be started for paralyzed limbs
• Frequent turning, alternating pressure mattresses & close observation of skin will decrease chance of pressure
sores
• Fall precautions should be taken during mobilization
Oxygenation
• Administration of supplementary O2 to hypoxemic stroke patients is recommended
- Not recommended in hospitalized nonhypoxic patients w/ acute ischemic stroke
• Target oxygen saturation level: >94%
• Provide ventilatory support if upper airway is threatened or sensorium is impaired
• Available data at present do not support routine use of hyperbaric oxygen in the management of acute ischemic
stroke patients
• Brief moderate hyperventilation (pCO2 target 30-34 mmHg) for patients w/ acute severe neurological decline
from brain swelling may be considered as aid to more definitive management
B196
F SUPPORTIVE CARE & REHABILITATION (CONT'D)

Glucose Control
• Goal is to achieve normoglycemia
• Persistent hyperglycemia post stroke is associated w/ poor outcome; treat hyperglycemia to achieve blood
glucose levels in the range of 6.0-10 mmol/L (108-180 mg/dL)
• Insulin may be considered for patients w/ acute ischemic stroke when the serum glucose level is >180 mg/dL;
close glucose monitoring is recommended to avoid hypoglycemia
• Hypoglycemia (blood glucose <3.3 mmol/L or <60 mg/dL) should be treated in patients w/ acute ischemic
stroke
Body Temperature
• Fever in the setting of acute ischemic stroke is associated w/ poor neurological outcome
• The source of any fever following stroke must be identified; fever should be treated w/ antipyretic agents &
cooling blankets if available
• Maintain normothermia
Volume Expansion
• Hemodilution by volume expansion is not recommended for treatment of patients w/ acute ischemic stroke
Drug-Induced Hypertension
• Usefulness among ischemic stroke patients is not well established
Nutrition & Hydration
• Malnutrition & dehydration may slow down recovery
• Enteral nutrition should be initiated within 7 days of admission after an acute stroke
• IV fluids should be administered initially in patients w/ acute stroke to maintain a balanced fluid status
- Avoid dextrose-containing solution
- Acute ischemic stroke patients are predominantly either euvolemic or hypovolemic at presentation
- If euvolemic at presentation, start maintenance fluids (estimated at 30 mL/kg body weight)
- If hypovolemic at presentation, careful fluid replacement is reasonable using isotonic solutions (0.9% saline
ISCHEMIC STROKE
solution), w/ extra precaution in patients vulnerable to volume overload (eg patients w/ heart or renal failure)
• Assess for the presence of dysphagia
- A water swallowing test is warranted prior to allowing patients to eat or drink
- Start nasogastric tube (NGT) feedings early within 48-72 hours in patients w/ signs of dysphagia, altered
sensorium, or in those unable to consume sufficient quantities of food or fluids orally
• In patients who cannot take solid food or liquids orally, it is reasonable to use nasogastric tube over endoscopic
gastrostomy tube until 2-3 weeks after stroke onset
• In conscious patients w/ varying degrees of dysphagia
- Oral feeding may progress to thickened liquids or semisolids upon careful assessment & recommendations
by the rehab physician &/or speech therapist
- Gradually introduce mechanically soft, blended diet & eventually regular diet
Rehabilitation
• All persons w/ stroke should be assessed for their rehabilitation needs
- Prevention of complications: Swallowing problems, skin breakdown, DVT, bowel & bladder dysfunction,
malnutrition, pain, contractures
- Assessment of impairments: Communication & motor impairments, cognitive deficits, visual & spatial
deficiency (eye movements, visual field, perceptual deficits), psychological deficits, sensory deficits
• Once patient is stable, an individualized rehabilitation program should be started to prevent long-term
complications
- Early rehabilitation interventions during hospital stay should be considered for eligible patients
- Based on some evidences from trials, Cerebrolysin may be given in addition to rehabilitation in the first 7
days after moderate to severe acute ischemic stroke
- Studies showed that very early mobilization (<24 hours) may affect the outcome & thus should be avoided
• Rehabilitation process should include:
- Prevention & management of comorbid illnesses
- Training for maximum independence
- Helping patient & family w/ psychological coping & adaptation
- Promote community integration
• Improves quality of life if disabilities are present
- Prevention of recurrent stroke or other vascular events
• A tailored home exercise program is recommended after completion of stroke rehabilitation program
B197
PRIMARY PREVENTION
Lifestyle Modification
• Consumption of diet rich in fruits & vegetables, & low in fat (especially saturated fat) & sodium
• Weight loss for overweight patients
• Regular aerobic exercise ≥30 minutes/day or >150 minutes/week, on most days of the week, depending on
patient’s level of fitness
- A pre-exercise evaluation should be done on stroke survivors to determine contraindications or special
medical conditions & neurological complications that may need special attention
• Moderate intake of alcohol for those who drink alcohol
- Limit to <1 drink/day
Smoking Cessation
• Smoking is a major independent risk factor for ischemic stroke
• Advise patient to quit smoking & avoid passive or environmental tobacco smoke
- Smoking cessation is a significant factor in both primary & secondary prevention of stroke
• Intervention initiation should be considered which incorporates behavioral & pharmacological support
Hypertension
• Regular BP monitoring is recommended
• Lifestyle modification is advised for patients w/ BP of 130-139/80-89 mmHg & are reassessed after 3-6 months
• Cardiovascular (CV) disease risk stratification is warranted to maximize treatment regimen
• Hypertensive elderly >80 years of age should be treated
Diabetes Mellitus
• More stringent BP control & HbA1c targets are important to prevent stroke
- Target BP <130/80 mmHg, if tolerated SBP <120 mmHg
Dyslipidemia
• Stratify patient's risk & follow guideline-recommended target levels & lipid-lowering therapy
ISCHEMIC STROKE
G SECONDARY PREVENTION
• Includes interventions aimed at preventing recurrent stroke
Antiplatelets
• Long-term antiplatelet therapy reduces the risk of serious vascular events (eg recurrent stroke, MI or vascular
death) following ischemic stroke or TIA
• Studies have shown that each of these antiplatelet agents are effective for secondary prevention of stroke
• Choice of agent is based on relative effectiveness, patient characteristics & preferences, safety, cost, risk factors,
tolerability, potential for drug interactions
• Aspirin alone, Dipyridamole plus Aspirin, or Clopidogrel alone is recommended for prevention in patients w/
non-cardioembolic ischemic stroke or TIA
• Not recommended in cases of non-valvular atrial fibrillation stroke prevention
Aspirin
• Most widely studied antiplatelet agent
• Benefits of Aspirin in the long-term preventive therapy of non-cardioembolic stroke are well established
Aspirin/Dipyridamole
• Combination of Aspirin & Dipyridamole may be superior to Aspirin alone in the secondary prevention of stroke
• Less well tolerated than Aspirin & Clopidogrel mainly because of headache
Clopidogrel
• May be used as 1st-line agent in patients unable to tolerate Aspirin & Dipyridamole
• Associated w/ fewer gastrointestinal & central nervous system events including gastric & intracranial hemorrhage,
but slightly more frequent skin rash & diarrhea compared w/ Aspirin
Aspirin/Clopidogrel
• Combination may be used in patients w/ acute coronary syndrome
• Has additional efficacy compared w/ Aspirin monotherapy in reducing the risk of stroke in the first 90 days & does
not increase the risk of hemorrhage among patients w/ minor ischemic stroke or TIA when given for 21 days
• Less effective than Warfarin in stroke prevention of patients w/ nonvalvular atrial fibrillation (AF)
Cilostazol
• A phosphodiesterase-3 inhibitor used as one of the treatment options in patients w/ a history of non-cardioembolic
ischemic stroke or TIA
• Some studies have shown its efficacy & safety in secondary stroke prevention among Asians w/ peripheral arterial
disease
B198
G SECONDARY PREVENTION (CONT'D)

Antiplatelets (Cont'd)
Ticlopidine
• Shown to be effective for the prevention of vascular outcomes in patients w/ cerebrovascular disease
• Can be an option for patients w/ recurrent stroke symptoms despite Aspirin use
• Rates of gastrointestinal bleeding are comparable or less than w/ Aspirin
• Associated w/ thrombotic thrombocytopenic purpura, aplastic anemia, neutropenia, agranulocytosis
Triflusal
• Has been shown to be non-inferior to Aspirin in preventing stroke/MI/vascular death & w/ less risk of
hemorrhagic complications
• Combination w/ Acenocoumarol is more effective in reducing risk of stroke in patients w/ nonvalvular AF w/
moderate to high risk of stroke than Acenocoumarol monotherapy
Secondary prevention in select patients
Oral Anticoagulants
• It is reasonable to initiate oral anticoagulation within 14 days after the onset of neurological symptoms for
most patients w/ a stroke or TIA w/ low risk of hemorrhagic conversion in the setting of AF
- May delay initiation of oral coagulation beyond 14 days if there is a high risk for hemorrhagic conversion (ie
large infarct, hemorrhagic transformation on initial imaging, uncontrolled hypertension or hemorrhagic
tendency)
• Recommended in patients w/ cardioembolic ischemic stroke or TIA
• Recommended for patients w/ moderate to high risk AF-associated stroke (CHA2DS2-VASc1 score = 1 not
due to female gender; CHA2DS2-VASc1 score ≥2) without recent unprovoked bleeding or ICH
Apixaban
• A direct & competitive factor Xa inhibitor, indicated for the prevention of 1st & recurrent stroke as well as
systemic embolism in a patient w/ nonvalvular AF
• Alternative to Aspirin in patients w/ nonvalvular AF deemed unsuitable for vitamin K antagonist w/ similar
ISCHEMIC STROKE
bleeding risk as that of Aspirin
• Alternative to Warfarin in nonvalvular AF patients deemed appropriate for anticoagulant therapy
• A dose of 5 mg twice daily is given for those who have ≥1 additional risk factor & no more than one of the
following characteristics: Age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL
- Above dose is more effective than Aspirin or Warfarin in patients w/ nonvalvular AF w/ moderate risk for
embolism; risk of ICH is low
- Dose is halved (2.5 mg twice daily) for those who have ≥2 of the above characteristics
Dabigatran
• A direct thrombin inhibitor approved for the prevention of first & recurrent stroke & systemic thromboembolism
in patients w/ nonvalvular AF & at least 1 additional risk factor
- Recommended in AF patients who are at intermediate to high risk (CHADS2 score1 ≥1) of stroke/systemic
embolism
• A study conducted in >18,000 patients w/ AF showed that Dabigatran, given at a dose of 150 mg twice daily,
showed lower rates of stroke or systemic embolism & less frequent ICH (but w/ similar rates of major bleeding)
compared w/ Warfarin
• Dabigatran given at 110 mg 2x a day had similar rates of stroke as Warfarin but w/ significantly less major
bleeding
Edoxaban
• A factor Xa inhibitor recommended for the prevention of 1st & recurrent stroke & systemic embolism in
patients w/ nonvalvular AF
• Requires initial therapy w/ parenteral anticoagulants prior to starting therapy
• Kidney function should be assessed prior to administration
- High creatinine clearance (>95 mL/min) may decrease efficacy
• Sudden discontinuation increases the ischemic event risks
1CHA
2DS2-VASc score represents the individual risk for stroke based on age ≥75, presence of vascular disease & increased risk of
stroke among patients w/ AF.
B199
G SECONDARY PREVENTION (CONT’D)

Oral Anticoagulants (Cont'd)
Rivaroxaban
• A factor Xa inhibitor recommended for the prevention of first & recurrent stroke & systemic embolism in
patients w/ nonvalvular AF who are at moderate to high risk of stroke (prior history of TIA, stroke or systemic
embolization or ≥2 additional risk factors)
- As effective as Warfarin in preventing cerebral or systemic embolism in patients w/ nonvalvular AF but has
a lower risk of intracranial bleeding
Vitamin K Antagonist
• Indicated for the prevention of stroke in patients w/ nonvalvular AF
• A target INR of 2-3 is recommended in patients w/ ischemic stroke or TIA w/ paroxysmal, persistent or
permanent AF
Warfarin
• Recommended for use in patients w/ AF, mechanical prosthetic heart valves &/or other potential sources of
cardioembolism, & also for stroke prevention in patients w/ nonvalvular AF
• Patients w/ large cardioembolic stroke may start Warfarin 2 weeks from stroke event because of risk of
hemorrhagic transformation
• Risk of serious cerebral hemorrhage; close monitoring is required
• Combination w/ antiplatelet therapy is not recommended for all patients after ischemic stroke or TIA but is
reasonable in patients w/ clinically apparent coronary artery disease
Antihypertensive Agents
• Choice of antihypertensives & target BP level should be individualized; average reduction of 10/5 mmHg
has been shown to be beneficial w/ reduction of stroke by 30-40%
- ACE inhibitor-based therapy helps reduce the risk of recurrent stroke in both hypertensive & normotensive
individuals
• BP of >140/90 mmHg has been defined by current guidelines as reasonable threshold to improve long-term
control in neurologically stable patient
Antihyperlipidemic Agents
ISCHEMIC STROKE
Statins
• Patients already on statins at the time of stroke should continue taking them
• Recommended to reduce the risk of stroke & cardiovascular events for patients w/ ischemic stroke or TIA
who have evidence of atherosclerosis, an LDL level of ≥2.6 mmol/L (≥100 mg/dL) & w/ no known coronary
heart disease (CHD)
• Goal in patients w/ atherosclerotic ischemic stroke or TIA & without known coronary heart disease is ≥50%
reduction in LDL or a target LDL of <1.8 mmol/L (<70 mg/dL) to achieve maximum benefit
Other Drugs
• May be administered to patients who do not tolerate statins
• Patients w/ hypertriglyceridemia or low HDL levels may be treated w/ Niacin or Gemfibrozil
• Fibrates should be strongly considered in patient w/ severe hypertriglyceridemia
- Fibrates lower triglyceride levels by 30-50% & may increase HDL cholesterol
- Fenofibrates are the preferred fibrates to use in combination w/ a statin since they have a lower risk of causing
myopathy
REVASCULARIZATION PROCEDURES
Carotid Endarterectomy (CEA)
• As a primary prevention strategy, it may be considered in asymptomatic patients w/ a 70-99% carotid stenosis
& procedure done by surgeons w/ morbidity/mortality rate at <3%
• For secondary prevention, it may be done in patients w/ a 70-99% carotid stenosis w/ recent ischemic events
(<180 days or within 2 weeks) without severe neurological deficit
- Procedure should be done in centers w/ <6% perioperative stroke & deaths complication rate
• Antithrombotic therapy should be continued pre- & post-surgical procedure
• It is not recommended for carotid stenosis <50%
Carotid Angioplasty or Stenting (CAS)
• An alternative to CEA for secondary prevention if surgery is inaccessible, undesirable or technically difficult
• Use of distal protection devices during the procedure & dual antiplatelets for 4 weeks after CAS is
recommended
• Risk of cerebral ischemia is increased w/ a complex anatomy of the aortic arch & internal carotid artery
Intracranial Angioplasty & Stenting (IAS)
• Role in acute ischemic stroke is still unclear & needs additional studies
B200
Dosage Guidelines

Drug Dosage Remarks
Direct Factor Xa Inhibitors
Apixaban Stroke prevention Adverse Reactions
in nonvalvular AF: • Hematologic effects (anemia, postprocedural hemorrhage including
5 mg PO 12 hrly post-op anemia & wound hemorrhage, contusion); Hepatic effects
or (elevated GGT & transaminases); GI effects (gingival hyperplasia,
2.5 mg PO 12 hrly1 nausea)
Edoxaban Stroke prevention • Contraindicated in patients w/ clinically significant active bleeding,
in nonvalvular AF: hepatic disease associated w/ coagulopathy leading to clinically
60 mg PO 24 hrly relevant bleeding risk
• Discontinue use in severe hemorrhage
Rivaroxaban Stroke prevention
in nonvalvular AF: • Monitor for signs of neurological impairment
20 mg PO 24 hrly • Use w/ caution in moderate to severe renal impairment, hepatic
w/ evening meal impairment, hip fracture surgery, congenital or acquired bleeding
disorders, uncontrolled severe arterial hypertension, active
ulcerative GI disease, recent GI ulcerations, vascular retinopathy,
recent intracranial hemorrhage or ICH, intraspinal or intracerebral
vascular abnormalities, epidural/spinal anesthesia or spinal
puncture, shortly after brain, spinal or ophthalmologic surgery,
women of childbearing potential
ISCHEMIC STROKE
Direct Thrombin Inhibitor
Dabigatran Stroke prevention Adverse Reactions
etexilate in nonvalvular AF: • Hematologic effects (hemorrhage, anemia, hematoma,
150 mg PO 12 hrly thrombocytopenia); Renal effect (hematuria); GI effects (dyspepsia,
Patients ≥80 yr or N/V, GI hemorrhage, abdominal pain, diarrhea, gastroesophagitis,
in >75 yr w/ ≥1 abnormal hepatic function); Other effects (wound secretion,
other risk factor for postprocedural discharge)
bleeding: Special Instructions
110 mg PO 12 hrly • Contraindicated in patients w/ severe renal impairment,
Co-administration hemorrhagic manifestations, bleeding diathesis, patients w/
w/ Dronedarone spontaneous or pharmacological hemostatic impairment, organ
or Ketoconazole lesions at risk of clinically significant bleeding (including
w/ moderate renal hemorrhagic stroke within the last 6 mth, patients on concomitant
impairment therapy w/ systemic ketoconazole, prosthetic heart valve
(Cr clearance replacement
30-50 mL/min): • Use w/ caution in hepatic impairment, renal insufficiency, increased
75 mg PO 12 hrly hemorrhagic risk, spinal/epidural anesthesia, lumbar puncture
• Discontinue use in patients who develop acute renal failure
1For patients w/ ≥2 of the following: Age ≥80 yr, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromole/L).

B201
Dosage Guidelines

Drug Dosage Remarks
Enzyme
Alteplase 0.9 mg/kg IV over Adverse Reactions
(rt-PA) 60 min w/ 10% of • Hematologic effects (hemorrhage especially from puncture sites, severe
total dose given as internal bleeding, intracranial hemorrhage has occurred); GI effects
initial bolus over (N/V); Other effects (fever, chills w/ back & abdominal pain)
1 min • Rarely: Allergic reactions (rashes, flushing, urticaria, anaphylactic
Max dose: 90 mg reactions)
• Infusion may be associated w/ hypotension
• Please see section on Evaluation for inclusion/exclusion criteria
• Patient should be in ICU or stroke unit for monitoring
• Neurological assessments should be done every 15 min during
infusion then every 30 min for next 6 hr then every hr until 24 hr
from treatment
• Measure BP every 15 min during the 1st 2 hr then every 30 min for
the next 6 hr then every hr until 24 hr from treatment
- Increase frequency of BP monitoring if SBP ≥180 mmHg or DBP
≥105 mmHg
• Should not be administered in patients receiving LMWH within
previous 24 hr
• If patient suffers severe headache, N/V, acute hypertension (signs of
possible intracranial hemorrhage):
ISCHEMIC STROKE
- Discontinue rt-PA if still being administered

- Obtain urgent CT scan
• Placement of nasogastric tubes, catheters or invasive procedures
may be delayed
Heparinoid
Sulodexide 600 LSU IM/IV Adverse Reactions
injection 24 hrly for • Injection: Occasionally pain, burn & hematoma at injection site
15-20 days then, • Oral: Occasionally GI disorders eg N/V, epigastralgia
continue treatment w/ Special Instructions
250-500 mg PO • Should be taken on an empty stomach, 30 min before meals
12 hrly for 30-40 days • Contraindicated in patients w/ hypersensitivity to heparin-like
Repeat treatment products, diathesis & hemorrhagic diseases
cycle at least twice yrly • Periodically monitor hemocoagulative parameters
Platelet Aggregation Inhibitors Excluding Heparin
Aspirin1 Acute phase Adverse Reactions
treatment: • GI effects (GI upset which may be minimized w/ food & w/ use of
160-325 mg PO as a enteric-coated formulation, GI irritation like erosion, ulceration);
single dose followed Hematologic effects (increase in bleeding time, decrease in platelet
by lower dose adhesiveness, hemorrhage); Hypersensitivity reactions
(50-325 mg) PO Special Instructions
24 hrly • Contraindicated in patients w/ active pathological bleeding (eg
Secondary peptic ulcer, intracranial hemorrhage), known allergy, hemophilia,
prevention: hemorrhagic disorders, severe renal or hepatic impairment
75-325 mg PO • Ensure benefit outweighs the risk before using concomitantly w/
24 hrly drugs that increase risk of bleeding (eg thrombolytics, NSAIDs)
1Combination of Aspirin 100 mg & Glycine 45 mg is available.

B202
Dosage Guidelines

Drug Dosage Remarks
Platelet Aggregation Inhibitors Excluding Heparin (Cont’d)
Aspirin/ Secondary Adverse Reactions
Dipyridamole prevention: • CNS effects (headache, fatigue, amnesia, seizure, confusion,
25/200 mg (1 cap) PO somnolence); GI effects (abdominal pain, dyspepsia, N/V,
12 hrly diarrhea, GI bleeding); Neuromuscular effects (arthralgia, back
pain, arthritis, myalgia); Hematologic effects (hemorrhage,
anemia, epistaxis); CV effects (cardiac failure, syncope); Other
effects (cough, hypersensitivity reactions)
• Contraindicated in patients w/ active pathological bleeding,
severe liver & renal impairments
• Use w/ caution in hypotension, unstable angina &/or recent MI
Cilostazol Secondary Adverse Reactions
prevention: • CNS effects (headache, dizziness, vertigo); GI effects (abnormal
100 mg PO 12 hrly stools, diarrhea, nausea, abdominal pain, flatulence); Resp
effects (rhinitis, pharyngitis, cough); CV effects (peripheral
edema, palpitation, tachycardia); Neuromuscular effects (back
pain, myalgia)
ISCHEMIC STROKE
• Contraindicated in patients w/ known predisposition to
bleeding, history of ventricular arrhythmias & heart failure of
any severity
• Use w/ caution in patients w/ severe hepatic & renal impairment
Clopidogrel Secondary Adverse Reactions
prevention: • Hematologic effects (hemorrhage, purpura, epistaxis; blood
75 mg PO 24 hrly dyscrasias, including neutropenia & thrombotic thrombocytopenic
purpura, have occurred); Dermatologic effects (rash, pruritus); GI
effects (abdominal pain, N/V, dyspepsia, constipation)
• Contraindicated in patients w/ active bleeding, severe liver
impairment
• Concurrent use of drugs known to inhibit CYP2C19 (eg
Omeprazole, Esomeprazole, Cimetidine, Fluconazole,
Ketoconazole, Voriconazole, Etravirine, Felbamate, Fluoxetine,
Fluvoxamine & Ticlopidine) should be avoided
- Separating the time of administration between the drugs does
not reduce the chance of interaction

B203
Dosage Guidelines

Drug Dosage Remarks
Clopidogrel/ Secondary prevention: Adverse Reactions
Aspirin Usual dose: • Hematologic effects (epistaxis, hematoma, bruising); GI
75 mg/100 mg (1 tab) PO effects (GI bleeding, diarrhea, abdominal pain, indigestion,
24 hrly for a max of heartburn; less commonly: N/V, constipation, gastric ulcer);
3 mth Other effects (headache, rashes, itching, dizziness, sensation
of tingling & numbness)
• May be taken w/ or without food
• Contraindicated in patients w/ asthma, runny nose, nasal
polyps, active bleeding (eg active gastric ulcer, intracranial
bleeding), severe liver & kidney disease
• Use w/ caution in patients at risk for bleeding (eg gastric
ulcer), those w/ blood disorders that predispose to extensive
bleeding, ischemic stroke in the last 7 days, presence of
mild-moderate kidney or liver disease, a recent serious injury
or a recent surgery
Ticlopidine Secondary prevention: Adverse Reactions
250 mg PO 12 hrly • Metabolic effects (elevation of cholesterol & triglyceride
levels); GI effects (diarrhea, N/V, dyspepsia, GI pain,
ISCHEMIC STROKE
flatulence, anorexia); Dermatologic effects (rash, purpura,

pruritus); Hematologic effect (neutropenia, thrombotic
thrombocytopenia have occurred); Hepatic effects (elevation
in alkaline phosphatase level, reports of hepatitis &
cholestatic jaundice)
• Contraindicated in patients w/ active pathological bleeding
[peptic ulcer disease (PUD), intracranial hemorrhage],
hemorrhagic diatheses, patients w/ history of
thrombocytopenia, neutropenia or agranulocytosis, severe
liver dysfunction
• CBC w/ differential & platelet counts should be taken at the
start of treatment then every 2 wk for the first 3 mth of
therapy & within 2 wk of discontinuation of Ticlopidine (if
discontinued within the first 3 mth of treatment)

B204
Dosage Guidelines

Drug Dosage Remarks
Triflusal Secondary prevention: Adverse Reactions
600-900 mg/day PO in • GI effects (dyspepsia, abdominal pain, N/V, constipation,
single or divided doses flatulence, anorexia); CNS effect (headache)
• Contraindicated in patients w/ active, antecedent or complicated
peptic ulcer, active bleeding & hypersensitivity to salicylates
• Use w/ caution in patients w/ hepatic & renal impairment
Warfarin Secondary prevention: Adverse Reactions
Individualize dose based • Hemorrhage can occur even within therapeutic INR levels
on PT ratio/INR • Less common effects: Cholesterol embolization (skin necrosis &
Initial dose: 2.5 mg PO purple discoloration of the toes); GI effects (N/V, diarrhea,
24 hrly hepatic dysfunction, pancreatitis); Other effects (alopecia, skin
Maintenance dose: reactions)
• Patients should be counseled on the risks of therapy along w/
drug & food interactions
• Avoid in patients w/ active or at risk of hemorrhage, active GI
ISCHEMIC STROKE
ulceration, severe wounds, cerebrovascular disorders & bacterial
endocarditis
• Use w/ extreme caution or not at all in patients w/ severe renal
or hepatic impairment
• INR monitoring is usually performed daily until the therapeutic
range (2.0-3.0) has been achieved
- Then INR is monitored 2-3 x/wk for 2 wk
- Then INR is monitored wkly or less often depending on the
stability of INR
NOOTROPICS & NEUROTONICS/NEUROTROPHICS

Drug Dosage Remarks
Peptide 10-50 mL IV infusion in Adverse Reactions
(Cerebrolysin normal saline solution • Hypersensitivity reactions
concentrate) (NSS) 24 hrly x 2-4 wk Special Instructions
[Porcine or • Contraindicated in patients w/ severe renal impairment,
brain-derived 5 mL IM or up to 10 mL status epilepticus, grand mal fits
peptide] IV 24 hrly x 2-4 wk
Citicoline 500 mg-2 g PO 24 hrly Adverse Reactions
or • CNS effects (insomnia, headache, dizziness); GI effects
250-1000 mg/day IM/ (nausea, anorexia)
slow IV up to 2 g/day Special Instructions
• Contraindicated in patients w/ parasympathetic hypertonia

B205
Myocardial Infarction w/
ST-Segment Elevation (1 of 26)
1
PATIENT IN THE COMMUNITY
Patient experiences ischemic-type chest discomfort
suggestive of acute myocardial infarction (AMI)
Does
patient have
heart disease or is No
patient at high risk
of AMI?
Yes
2
Has patient been
PATIENT previously instructed
INSTRUCTIONS Yes by healthcare provider on
• Glyceryl appropriate actions if AMI
trinitrate (GTN) is suspected?
• Aspirin
No
TRANSPORT PATIENT TO THE

EMERGENCY DEPARTMENT (ED)
A ED & acute care measures

B Pharmacological therapy - ED & acute care
• Aspirin
ALTERNATIVE
DIAGNOSIS
ACUTE CORONARY
3 SYNDROME
ACUTE
DIAGNOSIS • Please see Acute
TREATMENT Yes No
Coronary Syndromes
See next page Is AMI
confirmed? w/out Persistent
ST-Segment Elevation
disease management
chart for further
information
B206
Myocardial Infarction w/ ST-Segment Elevation (2 of 26)
ACUTE TREATMENT
OF AMI PATIENTS
B Pharmacological therapy - ED & acute care

Relief of Pain
• Opioid (IV)
Discontinue NSAID medication (except
Aspirin), if regularly taken prior to AMI
4
Patient is a ASSESSMENT
candidate Patient is a
Should patient receive
for IV candidate
IV thrombolytic therapy or
thrombolytic for PCI
percutaneous coronary
therapy intervention
(PCI)1?
C Routine measures for AMI patients C Routine measures for AMI
• Bed rest patients
• Patient monitoring • Bed rest
• Oxygen if SaO <90% • Patient monitoring
B Pharmacological2 therapy - ED & • Oxygen if SaO <90%
acute care B Pharmacological2 therapy - ED &
• Dual antiplatelet therapy (DAPT) acute care
• Fibrinolytic agents • DAPT
• Anticoagulants as ancillary therapy • High-intensity statins
• High-intensity statins D PCI
F Pharmacological therapy - further F Pharmacological therapy
inpatient treatment - further inpatient treatment
• Continue DAPT & statin therapy • Continue DAPT & statin therapy
initiated in ED initiated in ED
MYOCARDIAL INFARCTION
D PCI E Coronary artery

• Rescue PCI PHARMACOLOGICAL bypass graft (CABG)
- May be done in cases THERAPY - FURTHER • May be considered in cases
of failed thrombolytic INPATIENT of failed PCI or in cases not
therapy or TREATMENT amenable to PCI
• Routine early PCI See next page
(pharmacoinvasive
therapy)
- Preferably 3-24 hours
after successful
fibrinolysis
1PrimaryPCI is the preferred reperfusion strategy & should be used to treat STEMI patients promptly wherever possible. Consider IV
thrombolytic therapy if primary PCI cannot be performed in a timely manner.
B207
PHARMACOLOGICAL
THERAPY - FURTHER
INPATIENT TREATMENT
F Pharmacological therapy - further

inpatient treatment
• Antiplatelet therapy
• Anticoagulants1
• ACE inhibitors
• Angiotensin II antagonists (if intolerant
of ACE inhibitors)
• Beta-blockers
(Mineralocorticoid receptor antagonist)
• Nitrates2
• Calcium antagonists2
• High-intensity statins
5
RISK 6
STRATIFICATION Medium
Low
& High CONSIDER
risk AFTER THE ACUTE PHASE CORONARY
risk1
What is patient’s risk ANGIOGRAPHY
for future CV
events?
Does patient
G Non-pharmacological therapy have viable
• Patient education No
myocardium & suitable
• Cardiac rehabilitation anatomy?
• Risk factor management

H Pharmacological therapy - secondary
prevention Yes
• Antiplatelet therapy
• Anticoagulants (Oral)3
• ACE inhibitors CONSIDER
• Angiotensin II antagonists (if intolerant REVASCULARIZATION
of ACE inhibitors)
• Beta-blockers
(Mineralocorticoid receptor antagonist)
• Nitrates2
• Calcium antagonists2
• High-intensity statins
• Influenza vaccination
1For patients without primary PCI performed

2May be given if indicated
3May be considered in patients w/ atrial fibrillation or when indicated (eg left ventricular thrombus)
B208
1 PATIENT IN THE COMMUNITY

Acute Myocardial Infarction (AMI)
• Myocardial infarction is death of cardiac myocytes (necrosis) caused by prolonged ischemia
• The term “acute” usually refers to the time 6 hours - 7 days following pathologic appearance of the infarct
• Classified clinically as:
- Type 1: Acute atherothrombosis is demonstrated post-mortem in the artery supplying the infarcted
myocardium
- Type 2: Myocardial oxygen supply & demand imbalance not related to acute atherothrombosis
- Type 3: Cardiac death in patients w/ symptoms suggestive of myocardial ischemia & presumed new ischemic
changes on ECG prior to cardiac troponin values becoming available or abnormal
- Type 4a: Percutaneous coronary intervention (PCI)-related MI
- Type 4b: Stent or scaffold thrombosis associated w/ PCI
- Type 4c: Restenosis associated w/ PCI
- Type 5: Coronary artery bypass grafting (CABG)-related MI
• A prior or unrecognized/silent MI is a condition that has the following criteria:
- Abnormal Q waves w/ or without symptoms in the absence of non-ischemic causes
- Loss of viable myocardium on imaging consistent w/ an ischemic cause
- Patho-anatomical findings of a previous MI
• A recurrent MI is an MI occurring 28 days after an incident MI while a re-infarction is an acute MI occurring
within 28 days of an incident or recurrent MI
The patient may experience ischemic-type chest discomfort w/ the following characteristics:
• Retrosternal/substernal chest pain lasting 10-20 minutes or longer
- Pain is usually described as heaviness, pressure or burning in nature
- Pain may occur at rest or during activity & does not respond fully to Glyceryl trinitrate (GTN)
• The pain which is usually central or in the left chest may radiate to the jaw, neck, left arm, back or shoulder
• Discomfort is diffuse, not localized, positional nor affected by movement of the region
• Occasionally, symptoms are mistaken for indigestion or heartburn if pain occurs in the epigastric region
• Accompanying symptoms may include nausea, vomiting, dyspnea, diaphoresis, lightheadedness, dizziness,
syncope, fatigue & weakness
• Atypical patterns may occur especially in females, diabetics & elderly patients; the pain develops in the arm,
shoulder, wrist, jaw or back without occurring in the chest
• MI should be suspected especially if the symptoms are severe & occur suddenly
• MI may present w/ autonomic nervous system activation (eg pallor, sweating), hypotension or narrow pulse
pressure, bradycardia or tachycardia, 3rd heart sound (S3), basal rales or occasionally syncope in the elderly
2 PATIENT INSTRUCTIONS
• The patient should carry out previous instructions on medications to be taken in case of a possible MI:
Glyceryl Trinitrate (GTN)
• Patients w/ known coronary heart disease should take one dose of sublingual GTN
• Contraindicated in patients w/ hypotension &/or who have taken phosphodiesterase 5 inhibitor within 24-48 hours
• If symptoms do not subside in 10-15 minutes, take a second dose then seek emergency medical treatment in
the nearest hospital
Aspirin
• If patient is not on regular Aspirin & is not allergic, it is recommended that he chew & swallow 162-325 mg of Aspirin
• Enteric-coated form should not be used because of its slow onset of action
• If ECG shows STEMI changes, pre-hospital initial therapy should include soluble or chewable Aspirin &
Clopidogrel loading dose
3 DIAGNOSIS
Rapid diagnosis & risk stratification of chest pain patients are important to identify AMI patients who
will benefit from reperfusion therapy (ie reopening of the occluded artery)
Initial Diagnosis of STEMI
• Patient presenting w/ history of prolonged chest pain/discomfort, ie symptoms of acute myocardial ischemia
• ECG reveals new ischemic changes, persistent ST-segment elevations, (presumed) new left bundle-branch
block (LBBB), or pathological Q waves
- A decision to start treatment using PCI may be based on the patient’s clinical history & ECG results
Patient History
• Ischemic-type chest discomfort as described previously
B209
Initial Diagnosis of STEMI (Cont’d)
ECG
• Obtain & interpret as soon as possible, preferably within 10 minutes of emergency department (ED) arrival,
since even at the early stage, ECG is rarely normal
- If ECG shows ST-segment elevations or new or presumed new LBBB, then patient should be immediately
evaluated for primary PCI or if this cannot be performed in a timely manner by experienced operators, for
fibrinolytic therapy
- If resting ECG is without ST elevation or is non-interpretable (eg new RBBB, paced rhythm), consider
non-ST-segment elevation acute coronary syndromes (NSTE-ACS) (eg NSTEMI or unstable angina)
• ECG changes of AMI are evolutionary
- Hyperacute changes of a tall peaked T wave
- ST-segment elevation followed by development of Q wave
- In resource-limited settings, development of pathological Q waves can confirm the diagnosis of MI only
if the patient’s clinical history & previous ECG or cardiac biomarker results are available
- Then return of ST-segment to isoelectric & T-wave inversion
• ST segment elevation
- New or presumed new ST-segment elevation at the J point in 2 or more contiguous leads should be considered
at ≥0.2 mV for men ≥40 years, ≥0.25 mV for men <40 years, or ≥0.15 mV for women regardless of age in
leads V2-V3, &/or ≥0.1 mV in other leads
• ST-segment depression & T-wave changes
- New horizontal or downsloping ST-segment depression ≥0.05 mV in 2 contiguous leads
- T-wave inversion ≥0.1 mV in 2 contiguous leads w/ prominent R wave or R/S ratio >1
• ECG may be vague in the early hours & may not show ST-segment elevation or new Q waves
- Repeat or serial ECG should be taken to compare w/ previous records & detect evolving infarction
- Additional chest leads (V7-9) & right ventricular leads may be helpful
Confirmatory Tests for the Diagnosis of MI
• Elevated biochemical markers of myocardial necrosis
- Increase &/or decrease of cardiac troponin values w/ at least 1 value >99th percentile upper reference limit
(URL)
- These can confirm diagnosis in the absence of ECG changes
• 2D echocardiography & perfusion scintigraphy, if available, can be used to look for (presumed) new regional
wall motion abnormalities or loss of viable myocardium consistent w/ an ischemic cause
• Intracoronary thrombus identified by angiography or autopsy
Biochemical Indicators for Detecting Myocardial Necrosis
• Blood samples should be taken on 1st assessment & 3-6 hours later
- In the acute phase of STEMI, routine blood sampling for serum markers is indicated as soon as possible but
it should not delay initiation of reperfusion therapy
• Preferred biomarker for myocardial damage is cardiac troponin (T or I)
- High-sensitivity cardiac troponin (hs-cTn) assays have higher negative predictive value for AMI than standard
assays & hs-cTn levels >5-fold the URL have high positive predictive value for acute type 1 MI
- hs-cTn assays are associated w/ a 2-fold increase in identifying type 2 MI, eg tachyarrhythmias, heart
failure
• If cardiac troponin assays are not available, CK-MB assay is the preferred alternative
- Maximal CK-MB exceeding the 99th percentile of the values for a reference control group on 2 consecutive
samples or
- Maximal value over 2x the upper limit of normal for the specific institution at least once during the 1st hour
following the index clinical event
- Values for CK-MB should rise & fall; if the values remain elevated without change this is typically not due to MI
• A diagnosis of reinfarction is supported by a value increase of ≥20% between 2 samples of troponins or CK-MB
collected 3-6 hours apart
Imaging
• Helpful in detecting wall motion abnormalities or loss of viable myocardium in the presence of elevated cardiac
biomarker values
• Without any delay to therapy, obtain chest X-ray
• Perform chest X-ray, transthoracic &/or transesophageal echocardiography, contrast computed tomographic
(CT) scan to differentiate STEMI from aortic dissection in a doubtful presentation
• Perform echocardiography to allow risk stratification of patients w/ chest pain upon ED arrival & in those
whose diagnosis is unclear & ECG is not diagnostic, especially in patients w/ LBBB or pacing & suspicion of
posterior STEMI w/ anterior ST-segment depressions
• Transthoracic echocardiography may provide evidence of focal wall motion abnormalities & facilitate triage
in patients w/ ECG findings that are difficult to interpret
B210
4 ASSESSMENT
• All patients w/ ischemic symptoms of ≤12 hours & persistent ST-segment elevation or new or presumed new
LBBB should undergo early mechanical (percutaneous coronary intervention or PCI) or pharmacological
(fibrinolytic) reperfusion therapy unless they have contraindications
• Primary PCI is the preferred reperfusion strategy & should be used to treat STEMI patients promptly wherever
possible
- Superior to fibrinolysis when done at an appropriate time & at experienced institutions
- Both primary PCI & fibrinolysis appear to have the same benefits in low-risk patients presenting within 3 hours
of symptom onset but primary PCI is preferred in those presenting w/ a symptom duration of 3-12 hours
• Goal is to administer reperfusion treatment within 30 minutes of patient arriving at hospital for fibrinolytic
therapy & within 90 minutes of patient arriving at hospital for PCI (door to wire crossing time)
• Patients who received primary PCI or fibrinolysis had better survival outcomes than those who did not receive
any reperfusion therapy
Primary PCI should be considered in the following patients w/:
• Contraindications to intravenous (IV) fibrinolytic therapy
• High-risk features or presenting w/ cardiogenic shock
• Symptom duration of >12 hours & ECG evidence of ongoing ischemia
- Consider a routine primary PCI in patients presenting 12-48 hours after onset of symptoms
• Consider routine early PCI within 3-24 hours post-fibrinolysis as part of pharmacoinvasive strategy
In institutions that are experienced in PCI (stenting &/or angioplasty)
• STEMI diagnosis to wire crossing should be within 90 minutes
• For primary PCI, stenting is recommended over balloon angioplasty
In institutions that are not experienced in PCI
• If patient is transferred from a non-PCI-capable center, wire crossing should be performed within 120 minutes
from STEMI diagnosis
- If unable to meet target time for primary PCI (ie >120 minutes), consider pre-hospital or nearest in-hospital
fibrinolytic therapy within 12 hours of onset of symptoms then transfer patient to a PCI-capable center for
pharmacoinvasive treatment strategy
• If there are no contraindications, fibrinolytic therapy should be started within 30 minutes in STEMI patients initially
presenting to a hospital without PCI capability & who cannot be transferred to a PCI center in a timely manner
- Bolus administration of fibrinolytic therapy should be within 10 minutes from STEMI diagnosis
• Careful individual assessment needs to be made of the potential benefits of mechanical reperfusion vs risks of
treatment delay & transportation to the nearest interventional catheterization lab
Inclusion Criteria for IV Fibrinolytic Therapy
• Symptoms consistent w/ AMI
• ST-segment elevation on ECG
• New or presumably new bundle-branch block (that is obscuring ST-segment analysis) & history of MI symptoms
• If unable to perform primary PCI in a timely manner, ie first medical contact in a PCI center w/ door to balloon
time (DBT) of >90 minutes or in a non-PCI center w/ DBT of >120 minutes
• Time to therapy from onset of angina: <12 hours; most beneficial if <6 hours (golden hour is <2 hours)
- No significant benefit if >12 hours, except in patients w/ ongoing ischemia & ST-segment elevation on ECG
Absolute Contraindications
• Previous hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke within 3 months except acute ischemic stroke within 4.5 hours
• Known intracranial neoplasm or CNS damage
• Significant closed-head or facial trauma within 3 months
• Known structural cerebral vascular lesion (eg arteriovenous malformation)
• Aortic dissection (confirmed or suspected)
• GI bleeding within the last month
• Active bleeding or bleeding diathesis (does not include menses)
• Surgery within 2 months intracranially or intraspinally
• Severe uncontrolled hypertension that is unresponsive to emergency therapy
• For Streptokinase: Prior treatment within the previous 6 months
Relative Contraindications
Risks vs benefits must be considered
• Uncontrolled or refractory hypertension on presentation (SBP >180 mmHg &/or DBP >110 mmHg); history
of severe uncontrolled hypertension
• Transient ischemic attack within >3 months
• Taking oral anticoagulants
• Traumatic or refractory resuscitation
• For Streptokinase/Anistreplase: Prior exposure (especially within 5 days-12 months) or prior allergic reaction
- Antibodies may be present & can impair the action of the agent
B211
4 ASSESSMENT (CONT’D)
Relative Contraindications (Cont’d)
• Pregnancy
• Active peptic ulcer disease
• Advanced liver disease
• Dementia
• Major surgery within <3 weeks
• Internal bleeding within 2-4 weeks
• Non-compressible vascular punctures
• Identifying patients who are at increased risk of further reinfarction or death is essential in order that it can
be prevented or intervention can be done accordingly
- Referral of high-risk patients to specialty centers should be made for early coronary angiography &
revascularization
• Risk stratification of post-STEMI patients can be done clinically or by using the GRACE or the Thrombolysis
in Myocardial Infarction (TIMI) risk scores
High-Risk Patients
• Left ventricular ejection fraction (LVEF) <35%, ischemia that affects >50% of viable myocardium, post-revascularization
(PCI or CABG)
• Clinical indicators include:
- Advanced age
- Hypotension & cardiogenic shock
- Anterior infarction
- Elevated initial serum creatinine
- Malignant arrhythmias
- Early angina on minimal exertion/post-infarct angina
- Tachycardia
- Killip class >1
- Previous infarction
- Heart failure history
- Persistent chest pain
- Peripheral arterial disease
Medium-Risk Patients
• Patients not considered low risk or high risk based on imaging criteria should be treated based on symptomatic
status
Low-Risk Patients
• LVEF >50% or mild inducible ischemia that affects <20% of viable myocardium
6 CORONARY ANGIOGRAPHY
• In high-risk patients & medium-risk patients w/ angina, consider doing a coronary angiogram as part of further
investigation of coronary artery status
• Perform coronary angiogram in the following conditions if revascularization is a realistic option w/ intent to
do PCI or emergency CABG:
- Inducible ischemia
- Post-infarct angina
- LV arrhythmias
- LVEF ≤35% w/ significant regional wall motion abnormalities
- TIMI risk score ≥6
• Recommended in patients who have received fibrinolytic therapy & have the following:
- Cardiogenic shock in patients <75 years old who are candidates for revascularization
- Severe congestive heart failure (CHF) &/or pulmonary edema
- Life-threatening ventricular arrhythmias
• Invasive coronary angiography may be considered in all patients as part of pharmacoinvasive strategy after
fibrinolytic therapy & PCI can be done 3-24 hours after fibrinolysis
• Not recommended in patients who have received fibrinolytic therapy if further invasive management (PCI or
CABG) is contraindicated or is against patient’s or designee’s wish
B212
A EMERGENCY DEPARTMENT (ED) & ACUTE CARE MEASURES

• Secure venous access
• Record pulse & BP
Do pertinent lab exams promptly
• Do 12-lead ECG within 10 minutes
• Draw blood for cardiac biomarkers, full blood count, glucose, renal & lipid profile
Administer O2
• O2 at 2-4 L/min should be administered (preferably within 6 hours) to all patients & especially to patients who
have features of HF or shock, have SaO2 <90%, or are breathless
- Administer via nasal prongs or face mask
Reassure patient & caregiver
• Patient will probably have anxiety from the thought of a heart attack & from the pain
• It is helpful to reassure the patient & their caregivers; this may decrease their anxiety
B PHARMACOLOGICAL THERAPY - ED & ACUTE CARE

Relief of Pain
• Tranquilizer may be helpful in anxious patients
• NSAIDs (except Aspirin) & COX-2 inhibitors should be discontinued, if regularly used prior to AMI, due to
association w/ increased CV risk & prothrombotic effects
Opioid (IV)
• Eg Morphine (analgesic of choice for STEMI-related pain), Diamorphine
• Should be administered selectively for severe pain at the time of diagnosis
• Pain is associated w/ sympathetic activation that results in vasoconstriction & an increase in the workload of the heart
• Avoid IM administration
• Use w/ caution in inferior wall or posterior wall MI
• Anti-emetics may be given concurrently w/ opioids to minimize nausea
Antiplatelet Therapy
• DAPT is recommended in patients w/ STEMI who are undergoing primary PCI & for patients undergoing
fibrinolysis & subsequent PCI
• In the acute phase of STEMI, a loading dose of Aspirin & Clopidogrel, Prasugrel or Ticagrelor may be given
for patients undergoing primary PCI; for those receiving fibrinolytic therapy, a loading dose of Aspirin &
Clopidogrel may be given
Aspirin
• Should be given promptly & ideally within the 1st 24 hours of suspected MI unless there are
contraindications
• When dose >160 mg is given, Aspirin gives rapid clinical anti-thrombotic action which is caused by near-total
& immediate inhibition of thromboxane A2 production
• Treatment of evolving acute MI w/ Aspirin w/ or without thrombolytics has shown to reduce mortality
Reperfusion w/ Thrombolytic Therapy (IV)
• IV thrombolytics should be administered to patients w/ minimum delay in those w/ confirmed MI & do not
have contraindications
- “Door to needle” time should be within 30 minutes from arrival at the hospital
- The most benefit is seen when administered <6 hours after onset of symptoms
- Lesser, but still important benefit is seen when given 6-12 hours after onset of symptoms
- Should not be given >12 hours after symptom onset except in patients w/ ongoing ischemia
• Proven to decrease morbidity & mortality when acute MI is treated promptly w/ Aspirin & thrombolytic regimens
• Choice of agent will depend on an individualized assessment of risk & benefit, availability & cost
- Fibrin-nonspecific agents (eg Streptokinase & Anistreplase)
- Fibrin-specific agents [eg Alteplase (t-PA), Reteplase (r-PA), Tenecteplase (TNK-tPA)]
- For late-treated patients (>6 hours) or patients w/ hypotension, LV failure, or cardiac arrest, fibrin-specific
agents are preferred
• Monitor ST elevation, cardiac rhythm, clinical symptoms 1-3 hours after thrombolytic therapy
Fibrinolytic Agents
• Alteplase
- Fibrin specific & has better reperfusion at 90 minutes
- Heparin should be given for 48 hours due to high rate of reocclusion
• Streptokinase
- Not fibrin specific & less efficacious than fibrin-selective agents
- Antigenic & promotes antibody production
• Tenecteplase
- 2nd generation fibrin-specific agent that has a slightly lower bleeding risk
- Given as single or double bolus injections that do not induce production of antibody
- Heparin or Enoxaparin should be given after completing fibrinolytic therapy & continued for at least 48 hours
B213
B PHARMACOLOGICAL THERAPY - ED & ACUTE CARE (CONT’D)

Ancillary Therapy
• Patients undergoing reperfusion w/ thrombolytic therapy should be given anticoagulant therapy for ≥48 hours
up to 8 days
- If anticoagulant therapy should be given >48 hours, UFH should be used w/ caution because of the small
risk of Heparin-induced thrombocytopenia
- UFH, Enoxaparin & Fondaparinux have established efficacy as ancillary anticoagulant regimens
• Patients undergoing reperfusion w/ primary PCI should be given supportive anticoagulant therapy during the
procedure only
- UFH, Enoxaparin, Bivalirudin are recommended
- If Fondaparinux is used, anticoagulant w/ anti-IIa activity (eg UFH, Bivalirudin) should be added
Anticoagulants
• Unfractionated Heparin (UFH)
- Important adjunctive therapy after tPA-derived agents [(t-PA), (r-PA), (TNK-tPA), Streptokinase or
Anistreplase]
- IV UFH for 48 hours & continue in patients at high risk of thromboembolism
- If patient is at high risk of venous thromboembolism (VTE), they should receive IV UFH for 48 hours then
consider converting to SC Heparin, Warfarin or Aspirin
- High-risk patients: Anterior MI, existing heart failure (HF), previous embolus, atrial fibrillation or left
ventricular (LV) thrombus
• Bivalirudin
- Useful supportive anticoagulant for primary PCI w/ or without prior treatment w/ UFH
- Can be considered in STEMI patients who will undergo PCI & are at high risk of bleeding or have a history
of heparin-induced thrombocytopenia
- Not recommended as an alternative to UFH in patients who received thrombolytic therapy w/ Streptokinase
to avoid excess major bleeding
• Enoxaparin
- Can also be used to support rescue PCI
- No additional anticoagulant needed
- Use is indicated for patients w/ creatinine <2.5 mg/dL (190.6 µmol/L) in men & <2.0 mg/dL (152.5 µmol/L)
in women
- Preferred over UFH for anticoagulation extending beyond 48 hours
• Fondaparinux
- When used alone to support PCI, there is increased risk for catheter thrombosis, therefore, use of additional
anticoagulant w/ anti-IIa activity is warranted
- Use is indicated for patients w/ creatinine <3.0 mg/dL (228.7 mmol/L)
Statin Therapy
• It is recommended to initiate high-intensity statins as early as possible in all patients w/ STEMI (unless
contraindicated) & maintain it long-term
• Studies show that giving a loading dose of Atorvastatin 80 mg in patients before primary PCI leads to a
significant reduction in MI & major adverse cardiovascular events (MACE)
C ROUTINE MEASURES FOR AMI PATIENTS

Bed Rest
• Adequate bed rest as indicated by the clinical status of the patient
• Uncomplicated cases
- Early ambulation is encouraged
- Patient may sit out of bed late on the 1st day & be allowed to use commode, perform self-care &
self-feeding
- Ambulation can start the next day (eg walking flat surface up to 200 meters & upstairs within a few days)
• Complicated cases (eg HF, shock or serious arrhythmias)
- Will need bed rest longer & physical activity should be increased gradually based on extent of myocardial
damage & symptoms
- Consider risk of thrombus formation & appropriate prophylaxis
Monitor Patient
• Vital signs, pulse oximetry & ECG should be continuously monitored
Oxygen
• Administer oxygen if patient has hypoxemia (SaO2 <90% or PaO2 <60 mmHg)
• In uncomplicated cases, O2 is usually needed only for the 1st day
B214
D PERCUTANEOUS CORONARY INTERVENTION (PCI)

• Appropriate use criteria for revascularization of culprit artery by primary PCI recommended by the American
College of Cardiology (ACC), American Association for Thoracic Surgery (AATS), American Heart Association
(AHA), American Society of Echocardiography (ASE), American Society of Nuclear Cardiology (ASNC),
Society for Cardiovascular Angiography and Interventions (SCAI), Society of Cardiovascular Computed
Tomography (SCCT), & the Society of Thoracic Surgeons (STS):
- Patients w/ STEMI or MI w/ new LBBB whose onset of symptoms occurred within the past 12 hours
- Onset of symptoms within the past 12-24 hours accompanied by severe acute heart failure, persistent ischemic
symptoms, or hemodynamic/electrical instability
- Stable patients w/ onset of symptoms within the past 12-24 hours without severe acute heart failure, persistent
ischemic symptoms, or hemodynamic/electrical instability
• Primary PCI performed within 12 hours of symptom onset may help effectively secure & maintain patency of
the coronary artery & may prevent some of the bleeding risks of fibrinolysis
• Appropriate use criteria for immediate revascularization of ≥1 nonculprit arteries during the same procedure
as primary PCI as recommended by the ACC, AATS, AHA, ASE, ASNC, SCAI, SCCT & STS:
- Presence of cardiogenic shock after PCI of culprit artery & PCI of ≥1 additional vessels
- In stable patients to be done immediately after primary PCI of culprit artery w/ ≥1 additional severe coronary
artery stenoses
- In stable patients to be done immediately after primary PCI of culprit artery w/ ≥1 additional intermediate
(50-70%) coronary artery stenoses
• Preferred when it can be performed in an experienced center within 90 minutes on hospital arrival (DBT within
90 minutes)
- Only hospitals that have an established interventional cardiology program should use primary PCI as a
routine treatment in patients w/ signs & symptoms of acute MI
• May be an option for patients w/ contraindications to thrombolytic therapy
- To be done within 12 hours of symptom onset
• May be performed in cases of recurrent MI, moderate to severe myocardial ischemia during recovery from
STEMI, hemodynamic instability after thrombolytic therapy
• Routine thrombus aspiration prior to primary PCI as well as routine thrombectomy during primary PCI are
not recommended
• Radial access is preferred over femoral access when it can be done by an experienced radial operator
• PCI may be performed on nonculprit arteries if the patient is at intermediate to high risk for STEMI on
pre-discharge noninvasive tests or if spontaneous ischemia is present
• Appropriate use criteria for revascularization of nonculprit arteries by PCI to be done during the same hospital
stay for treatment of a culprit artery by PCI or fibrinolysis as recommended by the ACC, AATS, AHA, ASE,
ASNC, SCAI, SCCT & STS:
- Spontaneous or easily provoked ischemic symptoms w/ ≥1 additional severe coronary artery stenoses
- Asymptomatic but positive for ischemia during non-invasive diagnostics & w/ ≥1 additional severe stenoses
- Asymptomatic patients w/ ≥1 additional severe coronary artery stenoses
- Asymptomatic patients w/ ≥1 additional intermediate coronary artery stenoses
- Asymptomatic patients w/ ≥1 additional intermediate stenoses & fractional flow reserve of ≤0.80
Rescue PCI
• PCI performed immediately after failed thrombolytic therapy in patients w/ continuing or recurrent myocardial
ischemia & hemodynamic instability
• For patients w/ STEMI who have received thrombolytic therapy but w/ persistent ST-segment elevation (<50%
resolution 90 minutes after treatment initiation), rescue PCI is preferred over repeat thrombolytic therapy or
no additional reperfusion therapy
- Appropriate use criteria for PCI after fibrinolysis as recommended by the ACC, AATS, AHA, ASE, ASNC,
SCAI, SCCT & STS include presence of perfusion failure or re-occlusion following fibrinolysis
- If possible, procedure should be done within 2 hours of identifying the lack in resolution of ST-segment
elevation
• Early PCI may also be considered post-fibrinolysis if the TIMI risk score for STEMI on admission is ≥6, or if
patient developed acute pulmonary edema or cardiogenic shock after initial presentation or has symptoms which
resolved completely & ST segment normalized spontaneously or after treatment w/ GTN or antiplatelets
B215
D PERCUTANEOUS CORONARY INTERVENTION (PCI) (CONT’D)

Drug-eluting Stents (DES) PCI
• For primary PCI, new-generation DES stents are preferred over BMS
• Reduce the risk of repeated target vessel revascularization compared w/ BMS
• There is an increased risk of stent thrombosis w/ premature discontinuation of dual antiplatelet therapy (DAPT)
Bare-metal Stents (BMS) PCI
• Used in patients w/ high risk of bleeding, inability to comply w/ 1 year of DAPT, or anticipated invasive or
surgical procedures in the following year
Pharmacoinvasive PCI
• Pharmacological reperfusion strategy done using fibrinolytic therapy followed by angiography w/ or without
PCI within 24 hours after a successful fibrinolysis in a PCI-capable health facility
E CORONARY ARTERY BYPASS GRAFT (CABG) SURGERY

• Very limited use in the acute phase of STEMI other than for cardiogenic shock
• Appropriate use criteria for revascularization of nonculprit arteries by CABG (to be done during the same
hospital stay for treatment of a culprit artery by PCI or fibrinolysis) recommended by the ACC, AATS, AHA,
ASE, ASNC, SCAI, SCCT & STS:
- Spontaneous or easily provoked ischemic symptoms w/ ≥1 additional severe coronary artery stenoses
- Asymptomatic but positive for ischemia during non-invasive diagnostics & w/ ≥1 additional severe stenoses
- Asymptomatic patients w/ ≥1 additional severe coronary artery stenoses
- Asymptomatic patients w/ ≥1 additional intermediate coronary artery stenoses
- Asymptomatic patients w/ ≥1 additional intermediate stenoses & fractional flow reserve of ≤0.80
• May be considered in the following:
- Failed PCI w/ persistent pain or hemodynamic instability in patients w/ coronary anatomy suitable for surgery
- Coronary occlusion not suitable for PCI
- At time of surgical repair of mechanical complications (eg ventricular rupture, acute mitral regurgitation or
ventricular septal defect)
• Optimal timing for CABG will depend on the clinical condition of the patient
F PHARMACOLOGICAL THERAPY - FURTHER INPATIENT TREATMENT

Dual Antiplatelet Therapy (DAPT)
• Eg Aspirin + Clopidogrel/Prasugrel/Ticagrelor (P2Y12 inhibitors)
• Aspirin should be administered daily & continued indefinitely to all patients without contraindications
• P2Y12 inhibitor therapy is given:
- Post-fibrinolysis for 1 month to 12 months depending on the ischemic versus bleeding risks
- After PCI (BMS or DES) for at least 12 months; after CABG, P2Y12 inhibitor therapy is resumed to complete
12 months of DAPT
- In patients at high risk of complications w/ severe bleeding, consider stopping P2Y12 inhibitors after
6 months
• Continuation of DAPT for >12 months may be reasonable if there is no high risk of bleeding & no significant
overt bleeding on DAPT
Aspirin
• Standard 1st-line antiplatelet therapy
• 75-100 mg/day of Aspirin is recommended after stenting, in patients w/ a prior MI or revascularization, & in
those being treated w/ DAPT
Clopidogrel
• In combination w/ Aspirin, Clopidogrel is recommended in STEMI patients receiving thrombolysis & in whom
a PCI is planned
• Should be given in STEMI patients up to 75 years of age who are receiving fibrinolysis, Aspirin & Heparin
• If CABG is to be performed, intake of Clopidogrel should be withheld 5 days prior to procedure
Prasugrel
• In combination w/ Aspirin, Prasugrel is recommended in STEMI patients in whom PCI is planned
• If CABG is to be performed, intake of Prasugrel should be withheld 7 days prior to procedure
B216
F PHARMACOLOGICAL THERAPY - FURTHER INPATIENT TREATMENT (CONT’D)

Antiplatelet Therapy (Cont’d)
Ticagrelor
• In combination w/ Aspirin, Ticagrelor is recommended in STEMI patients who have undergone PCI or medical
management
• Alternative to Clopidogrel in <75-year-old patients undergoing PCI within 24 hours after fibrinolytic therapy
• Should be withheld 3-5 days prior to CABG
Cangrelor
• A potent, direct, reversible & short-acting IV P2Y12 inhibitor
• May be used in P2Y12 inhibitor-naive patients undergoing PCI or patients who cannot take oral medications
or whose absorption of oral medications is inhibited
Glycoprotein IIb/IIIa Inhibitors
• Adjunctive use of Abciximab, Eptifibatide or Tirofiban at the time of primary PCI can benefit patients w/ large
thrombus burden
• Eptifibatide or Tirofiban should be discontinued at least 2-4 hours & Abciximab at least 12 hours before urgent
CABG
Anticoagulants (IV)
• Eg UFH, Enoxaparin, Fondaparinux
• Given to those who received fibrinolytic therapy but did not undergo PCI
• Beneficial in MI w/ ST elevation
- May also be given to patients treated w/ fibrin-selective lytic agents, as routine administration after fibrinolysis,
& patients w/ atrial fibrillation or mural thrombus
• When Fondaparinux is used alone to support PCI, there is increased risk for catheter thrombosis; therefore,
use of additional anticoagulant w/ anti-IIa activity (eg UFH or Bivalirudin) is warranted
ACE Inhibitors
• Start in all patients once the BP is stable & SBP remains >100 mmHg unless contraindicated (ideally within
the 1st 24 hours & after thrombolytic therapy)
- Greatest benefit has been seen in patients w/ HF, anterior infarction, LV systolic dysfunction, diabetes
• Associated w/ small but significant decrease in 30-day mortality w/ most of the benefit seen in the 1st week
after infarction
Angiotensin II Antagonists
• Use in patients who have indications for (eg early-phase HF or LVEF ≤40%) but are intolerant to ACE
inhibitors
Beta-Blockers
• Eg Atenolol, Bisoprolol, Carvedilol, Labetalol, Metoprolol, Propranolol
• Oral beta-blockers should be given within 24 hours of onset of infarction in low-risk patients without contraindications
(eg hypotension or evidence of low output state, CHF, increased risk for cardiogenic shock, PR interval >0.24
seconds, 2nd- or 3rd-degree heart block, active asthma or reactive airway disease)
• When given during 1st few hours of infarct, beta-blockers may lessen myocardial O2 demand by decreasing
HR, systemic arterial pressure & myocardial contractility
Aldosterone Antagonists (Mineralocorticoid Receptor Antagonists)
• Eg Eplerenone, Spironolactone
• When added to beta-blocker & ACE inhibitor, aldosterone antagonist has been shown to reduce mortality &
hospitalization rates in post-MI patients w/ impaired LV function & mild HF
Nitrates
• Nitrate-induced relaxation of the vascular smooth muscle in veins, arteries & arterioles results in vasodilation
- This reduces RV & LV preload along w/ afterload reduction which decreases cardiac work & myocardial O2 demand
• May be considered in the 1st 24-48 hours if needed in patients w/ continuing chest pain/ischemia, HF, large
anterior infarction or hypertension
- IV is usually preferred in early management (1st 48 hours) because of more precise control
• May be used beyond 48 hours if patient has recurrent angina or continued pulmonary congestion
Calcium Antagonists
• Eg Diltiazem or Verapamil
• Should only be considered if beta-blockers & nitrates are ineffective in controlling ischemia or if beta-blockers
are contraindicated
• May be used to control rapid ventricular response w/ atrial fibrillation after acute MI
• Have not been shown to reduce mortality after acute MI
• Should not be used in patients w/ CHF, LV dysfunction or AV block
B217
F PHARMACOLOGICAL THERAPY - FURTHER INPATIENT TREATMENT (CONT’D)

Statins
• High-intensity statins should be given as concomitant pharmacotherapy in the acute treatment of all STEMI
patients if without contraindications
Glucose Control
• Hyperglycemia is managed during the acute phase but hypoglycemic episodes should be avoided
G NON-PHARMACOLOGICAL THERAPY
Patient Education
• Patient & family should be educated about CVD
• Early warning signs of AMI & appropriate advice on seeking medical attention should be reviewed w/ the
patient & their family
• Encourage patients to adopt healthy lifestyle modifications & medication compliance prior to discharge &
review on each follow-up visit
• Family members are encouraged to undergo CPR training
Secondary prevention program includes:
• Baseline assessment of patient’s condition
- Patients w/ ischemia or arrhythmia are at high risk during cardiac rehabilitation
• Education & counseling on nutrition & management of lifestyle & medical risk factors
• Psychosocial health
• Physical activity
- Intensity of aerobic &/or resistance exercises should be identified based on patient’s risk stratification
• Drugs for secondary prevention
Risk Factor Management
Diet Modification
• Dietary interventions have been shown to be highly effective in preventing recurrent CV events in patients
w/ established CHD
- Compared to other interventions, dietary changes are very cost effective
• Primary goal: Overall healthy eating pattern
• All patients w/ increased risk of CHD should be given advice & specific recommendations on a healthy diet
- Family involvement especially the person buying &/or preparing the food is helpful
• Counsel the patient on the proper diet containing variety of fruits, vegetables, wholegrain cereals, bread,
low-fat or nonfat dairy products, legumes, fish, poultry & lean meats
- Reduce saturated fats <7% of total daily intake
- Reduce cholesterol intake to <200 mg/day
- Replace saturated fat partly by complex carbohydrates (grains), partly by monounsaturated & polyunsaturated
fats (vegetables & marine animals)
- Add plant stanol/sterols (2 g/day) &/or viscous fiber (>10 g/day) to diet which may help lower LDL-C
- Sodium intake should be <2.3 g/day
• Energy intake should be matched w/ energy needs
Increase Physical Activity
• Physical fitness has a direct protective effect on the development of vascular lesions
- Other risk factors are indirectly & positively influenced by physical fitness (eg lowering LDL-C, TG & raising
HDL-C along w/ reducing weight & BP)
• Minimum goal: 30-60 minutes of moderate intensity aerobic exercise at least 5x/week
• All patients should consult their physician prior to initiating vigorous exercise programs
- Patients w/ CVD will need to be assessed for risk, preferably w/ stress test prior to prescription of any
exercise program
- For high-risk patients, medically supervised rehabilitation programs may be considered
B218
G NON-PHARMACOLOGICAL THERAPY (CONT’D)

Risk Factor Management (Cont’d)
Weight Management
- Obesity also contributes to other CHD risk factors (eg hypertension, low HDL-C, glucose intolerance, etc)
- The presence of abdominal obesity particularly raises CV risk & waist circumference along w/ waist:hip ratio
should be evaluated
- Target waist circumference: <102 cm in men, <88 cm in women
• Weight management & exercise should be prescribed as appropriate in all overweight patients
• Goal BMI for Asian adults: 18.5-22.9 kg/m2, BMI for American/European adults: 18.5-24.9 kg/m2
• Initial goal is to reduce body weight by 10% from baseline
Smoking Cessation
• Cigarette smoking increases the risk for CV disease events
- Dose-dependent relationship exists between cigarettes smoked & CV risks
- Studies show that through smoking cessation, patients can reduce mortality in the succeeding years by at
least one-third compared to those who continue to smoke
• Primary goal: Complete smoking cessation
• Assess patient’s tobacco use & strongly urge patient & family to stop smoking
• Determine the patient’s degree of addiction & his/her readiness to quit smoking
- Identify which patients are willing to quit
- Quit plan should be developed & pharmacological therapy (eg nicotine replacement, Bupropion, Varenicline),
counseling & formal cessation programs should be provided, if needed
Moderation of Alcohol Consumption
• Alcohol has an acute effect in elevating BP
- High levels of alcohol consumption are associated w/ a high risk of stroke
• Primary goal: Patients who drink should limit alcohol intake to ≤20-30 g of ethanol/day for men & ≤10-20 g
of ethanol/day for women
H PHARMACOLOGICAL THERAPY - SECONDARY PREVENTION

• Aspirin
- Standard 1st-line antiplatelet therapy; daily administration should continue indefinitely in all patients unless
contraindicated
- Results in a significant reduction in mortality & nonfatal reinfarction & nonfatal stroke
- The addition of a second antithrombotic agent to Aspirin for long-term secondary prevention in patients
without high bleeding risk should be considered in those whose risk of ischemic events is high & may be
considered in those whose risk of ischemic events is at least moderately increased
- Ticlopidine may be considered as an alternative agent to Aspirin-intolerant patients
• Clopidogrel or Prasugrel
- In conjunction w/ Aspirin, should be given for at least 12 months in patients receiving a stent (BMS or DES)
during PCI
- If the risk of bleeding outweighs benefit, earlier discontinuation of either Clopidogrel or Prasugrel should
be considered
- Clopidogrel may be a useful substitute for Aspirin in patients who cannot tolerate Aspirin
• Ticagrelor
- In conjunction w/ Aspirin, it may be given for 12 months to patients who underwent stent implantation to
prevent thromboembolic events & >12 months (may consider for up to 3 years) to high-risk post-MI patients
who have tolerated DAPT for 12 months without bleeding complication
• Vorapaxar
- Newly approved protease activated receptor-1 (PAR-1) antagonist that inhibits platelet activation
- Studies showed that Vorapaxar, when given w/ other antiplatelet agents, significantly reduced incidences of
B219
H PHARMACOLOGICAL THERAPY - SECONDARY PREVENTION (CONT’D)

Anticoagulants (Oral)
• Eg Vitamin K antagonists (Warfarin) & non-vitamin K antagonists/direct oral anticoagulants
• Given to patients w/ atrial fibrillation or LV thrombus
• Warfarin
- Patients w/ LV thrombus may be treated for 3-6 months then reassessed
- Use of Warfarin w/ antiplatelet agents is associated w/ increased risk of bleeding & should be closely
monitored
• Direct oral anticoagulants
- Rivaroxaban may be given, in conjunction w/ Aspirin, to high-risk post-MI patients for >12 months (& up
to 2 years) or those w/ multivessel CAD
ACE Inhibitors
• ACE inhibitors should be continued indefinitely in patients w/ LV dysfunction
- May be given for >1 year in patients w/ LVEF ≤40%, anterior infarct or diabetes
• If patient has no evidence of symptomatic or asymptomatic LV dysfunction, ACE inhibitors may be stopped
in 4-6 weeks
- There may be a benefit to administering ACE inhibitors for at least 4-5 years even if a patient does not suffer
from ventricular dysfunction if the drug is tolerated
- This benefit may be even greater in DM patients after MI
• Decrease in mortality has been shown when ACE inhibitors were started soon after MI
- Patients w/ LV dysfunction (LVEF <40%), HF in the acute event, or wall motion index of ≤1.2 have seen the
greatest benefit
Angiotensin II Antagonists
• Continue in any patients intolerant of ACE inhibitors & w/ clinical or radiological signs of HF or LVEF <40%
Beta-Blockers
• Continue indefinitely in all post-MI patients for at least a year unless contraindicated
• Recommended in patients w/ systolic HF or LV dysfunction
- May be given for >1 year in patients w/ LVEF ≤40%
• Has been shown to reduce mortality from a reduction in sudden & non-sudden cardiac death
• Consider to give in patients who continue to experience angina after revascularization
Aldosterone Antagonist (Mineralocorticoid Receptor Antagonist)
• May be considered in post STEMI patients w/ LVEF <40% & HF or diabetes, provided that creatinine is <2.5 mg/
dL (221 mmol/L) in men & <2.0 mg/dL (177 mmol/L) in women & potassium is ≤5.0 mEq/L
• Monitor serum potassium & watch out for hyperkalemia
Nitrates
• Prophylactic sublingual GTN (tablet or spray) may be given to patients w/ continuous angina prior to engaging
in activities that will precipitate angina
Calcium Antagonists
• Consider to give in patients who continue to experience angina after revascularization
• May be considered in patients w/ contraindications to beta-blockers & do not suffer HF or LV dysfunction
• A randomized controlled trial in the chronic phase of STEMI showed reduction in the risk of reinfarction &
death w/ Verapamil in those not on beta-blockers
• Evidence of benefit is not as strong as for beta-blockers
Aggressive Lipid Lowering
• All post-STEMI patients should be started on high-intensity statin therapy, if without contraindications, to
achieve the following recommended treatment goal for LDL-C:
- Very high risk: <55 mg/dL (<1.4 mmol/L)
• Consider adding other non-statin therapy (eg Ezetimibe, PCSK-9 inhibitors) if target LDL-C levels are not
achieved
• On discharge, patients should be counseled about cholesterol-lowering diet recommendations
Blood Pressure Control
• In addition to lifestyle interventions including increased physical activity, weight loss & decreased salt intake,
pharmacotherapy should be initiated to obtain optimal blood pressure control
Glucose Control
• Target fasting blood glucose & glycosylated hemoglobin levels should be individualized
Influenza Vaccination
• Patients w/ cardiovascular disease should have an annual influenza vaccination
B220
Dosage Guidelines
ACE INHIBITORS
Drug Dosage Remarks
Adjust dose gradually according to response • CV effects (hypotension,
Max dose: 20 mg PO 24 hrly angioedema); CNS effects
(fatigue, headache); GI effects
Captopril Start 3 days after MI (taste disturbances, N/V); Resp
Initial dose: 6.25-12.5 mg PO 8 hrly effects (persistent dry cough,
Adjust dose gradually according to response upper resp tract symptoms);
Maintenance dose: 25-50 mg PO 8-12 hrly Dermatologic effects (skin
Max dose: 150 mg PO 24 hrly rashes, erythema multiforme,
toxic epidermal necrolysis);
Cilazapril Initial dose: 0.5 mg PO 24 hrly Hypersensitivity reactions;
Maintenance dose: 1-2.5 mg PO 24 hrly Renal effect (renal
Max dose: 5 mg PO 24 hrly impairment); Electrolyte
disturbances (hyperkalemia,
Enalapril Initial dose: 2.5 mg PO 24 hrly or divided 12 hrly hyponatremia); Blood disorders
Maintenance dose: 20 mg PO 24 hrly or divided 12 hrly Special Instructions
Max dose: 40 mg 24 hrly • Start w/ low-dose oral
Fosinopril Initial dose: 10 mg PO 24 hrly administration & increase
Adjust dose gradually according to response steadily to full dose within
24-48 hr (as tolerated)
Max dose: 40 mg/day
• Contraindicated in patients w/
Lisinopril Initial dose: 5 mg PO within 24 hr of infarct SBP <100 mmHg, in patients
Repeat 5 mg PO after 24 hr, then 10 mg after 48 hr w/ aortic stenosis or outflow
Maintenance dose: 5-40 mg PO 24 hrly tract obstruction & should
Patients w/ SBP ≤120 mmHg: 2.5 mg PO initially generally be avoided in
suspected or actual
Perindopril Initial dose: 4-5 mg PO 24 hrly x 2 wk renovascular disease
Maintenance dose: 8-10 mg 24 hrly • Use w/ caution in patients w/
Quinapril Initial dose: 2.5-5 mg PO 12-24 hrly history of hereditary or
Maintenance dose: 10-40 mg/day PO 24 hrly or idiopathic angioedema
divided 12 hrly • Renal function should be
Max dose: 40 mg/day assessed prior to
administration of ACE
Ramipril Initial dose: 2.5 mg PO 12 hrly inhibitors & should be
May start at 1.25 mg PO 12 hrly if w/ hypotension or monitored during therapy
patient cannot tolerate higher dose - Patient w/ renal disease or
Increase dose after 2 days to taking high doses should be
Maintenance dose: 2.5-5 mg PO 12 hrly monitored regularly for
Max dose: 10 mg 24 hrly proteinuria
Trandolapril Initial dose: 0.5 mg PO 24 hrly
May titrate up to 4 mg PO 24 hrly
Increase dose after 2 days to
Maintenance dose: 4 mg PO 24 hrly
Zofenopril Begin 24 hr after onset of acute MI symptoms &
continue dose for 6 wk
Initial dose: 7.5 mg PO 12 hrly for 2 days,
then 15 mg PO 12 hrly for 2 days,
then 30 mg PO 12 hrly onwards

B221
Dosage Guidelines
Drug Dosage Remarks
Candesartan Initial dose: Adverse Reactions
4 mg PO 24 hrly • Usually mild & transient: CNS effect (dizziness); CV effects
Increase by doubling (dose-related orthostatic hypotension which may occur
the dose ≥2 wk intervals particularly in patients w/ volume depletion, bradycardia);
to the highest dose renal impairment; Other rare effects: Rash, angioedema,
tolerated by the patient elevated LFTs; hypercalcemia, myalgia
Target dose: Special Instructions
32 mg PO 24 hrly • Patients w/ volume depletion (eg high-dose diuretic therapy)
may experience hypotension & should be started on low dose
Telmisartan 80 mg PO 24 hrly • Use w/ caution in patients w/ renal artery stenosis, renal
impairment or hepatic impairment
Valsartan Start ≥12 hr after MI: • Check BP, renal function & electrolytes 1-2 wk after each dose
Initial dose: increment at 3 mth then every 6 mth
20 mg PO 12 hrly - More frequent monitoring is necessary in patients w/ past or
Increase dose to 160 mg present renal dysfunction
PO 12 hrly as tolerated • The triple combination of ACE inhibitor, beta-blocker &
by patient angiotensin II antagonists should be avoided
ANTICOAGULANTS
Drug Dosage Remarks
Bivalirudin For patients who will Adverse Reactions
undergo PCI: • Hematologic effect (bleeding); Dermatologic effects
0.75 mg/kg IV followed (hypersensitivity reactions, pain on the inj site, severe anaphylaxis);
by an infusion of CV effects (hypertension, hypotension, bradycardia); GI effects
1.75 mg/kg/hr during (N/V, dyspepsia); Renal effect (urinary retention); Musculoskeletal
the procedure & up to effect (back pain); CNS effects (headache, anxiety)
4 hr post-procedure Special Instructions
If needed, may continue • Contraindicated in patients w/ active major bleeding, severe
infusion at 0.25 mg/kg/ renal impairment including dialysis-dependent patients
hr up to 12 hr • Use w/ caution in patients at high risk for bleeding, recent
major surgery, puncture of large blood vessels or organ biopsy,
hepatic dysfunction & moderate renal impairment

Fondaparinux 2.5 mg IV once daily on Adverse Reactions
first dose followed by • Hematologic effects (bleeding, anemia); GI effects (N/V,
2.5 mg SC once daily on constipation, diarrhea); CV effects (edema, hypotension,
subsequent doses x hypertension, chest pain, PCI guiding-catheter thrombosis); CNS
8 days or until hospital effects (insomnia, headache, dizziness, confusion);
discharge Dermatologic effects (rash, purpura)
• Do not administer via IM route
• Contraindicated in patients w/ significant bleeding, acute
bacterial endocarditis, hypersensitivity to the drug, severe
renal impairment & body wt <50 kg
• Use w/ caution in the elderly & in moderate renal impairment
• Avoid administration 24 hr before & 48 hr after CABG surgery
• Periodic monitoring of CBC & creatinine, & occult blood
testing of stools are recommended

B222
Dosage Guidelines
ANTICOAGULANTS (CONT’D)
Drug Dosage Remarks
Factor Xa Inhibitors (Cont’d)
Rivaroxaban 2.5 mg PO 12 hrly Adverse Reactions
Taken w/ an Aspirin dose of 75-100 mg PO • Hematologic effects (hemorrhage,
24 hrly thrombocytopenia, hematoma); Hepatic
effects (increased ALT & AST, cholestasis);
CNS effects (dizziness, headache, fatigue),
CV effect (hypotension); GI effects (N/V,
abdominal pain); Dermatologic effects
(pruritus, rashes); Other effects
(angioedema, postprocedural hemorrhage)
• Contraindicated in patients w/ active
pathologic bleeding or significant risk of
major bleeding, moderate to severe hepatic
impairment
• Use w/ caution in patients w/ hemorrhagic
risk, severe HTN, bronchiectasis, hepatic &
renal impairment
Low-Molecular-Weight Heparin Adverse Reactions
Enoxaparin Fibrinolytic therapy • Hematologic effects (hemorrhage,
<75 yr: thrombocytopenia); Rare hypersensitivity
reactions (anaphylaxis)
30 mg IV bolus initially, after 15 min,
follow w/ 1 mg/kg SC 12 hrly Special Instructions
Max dose: • Avoid in patients w/ active major bleeding,
patients w/ positive in vitro test for
100 mg for 1st 2 doses given SC antiplatelet Ab to the specific Heparin
≥75 yr: • UFH should not be given for >48 hr in the
No initial bolus, 0.75 mg/kg SC 12 hrly absence of current indication for
Max dose: 75 mg for 1st 2 doses anticoagulation
Regardless of age, if CrCl <30 mL/min: SC • Maintenance dose w/ Enoxaparin should be
regimen should be 1 mg/kg 24 hrly continued for 8 days
Unfractionated Heparin (UFH) • Use w/ caution in patients w/ hemophilia or
other hemorrhagic disorders (including
Heparin STEMI w/ fibrinolytic therapy: history of Heparin-induced
Patients receiving Alteplase, Tenecteplase, thrombocytopenia), peptic ulcer, recent
Reteplase, Streptokinase: cerebral hemorrhage, severe hypertension,
Initial dose: 60 units/kg IV bolus (max severe liver disease, post-major trauma or
dose: 4,000 units), followed by 12 units/kg/ recent surgery to brain, spinal or ophthalmic
hr IV infusion (max dose: 1,000 units) surgery, hypersensitivity to Heparin
Then, adjust to maintain aPTT at 1.5-2.0 x • Consider risk vs benefit before neuraxial
control for 48 hr intervention is employed in patients
STEMI w/ primary PCI: anticoagulated or to be anticoagulated for
Patients receiving Glycoprotein IIb/IIIa thromboprophylaxis
inhibitor: 50-70 units/kg [target activated • Monitoring of platelets is recommended at
clotting time (ACT): 200-250 sec] baseline & periodically during treatment
Patients not receiving Glycoprotein IIb/
IIIa inhibitor: 70-100 units/kg
(target ACT: 250-350 sec)

B223
Dosage Guidelines
ANTIPLATELET AGENTS
Drug Dosage Remarks
Aspirin1 Loading dose: Adverse Reactions
Chew 160-325 mg • GI effects (GI upset which may be minimized by
non-enteric-coated x 1 dose administering w/ food & w/ use of enteric-coated
Followed by: formulation, also GI irritation including erosion,
75-325 mg PO 24 hrly ulceration, etc); Hematologic effects (increase in bleeding
time, decrease in platelet adhesiveness, hemorrhage);
hypersensitivity reactions
• Contraindicated in patients w/ peptic ulcer or known
allergy
combination w/ Warfarin, Heparin, thrombolytics,
NSAIDs & other drugs that increase the risk of bleeding
Cangrelor 30 mcg/kg IV bolus prior to Adverse Reactions
PCI followed by 4 mcg/kg/ • Hematologic effect (hemorrhage/bleeding); Other effects
min continuous IV infusion (renal impairment, dyspnea, hypersensitivity reaction)
over at least 2 hr or for the Special Instructions
duration of the PCI, • Contraindicated in patients w/ active bleeding
whichever is longer • An oral P2Y12 platelet inhibitor must be administered
after Cangrelor infusion to maintain platelet inhibition
Clopidogrel Co-administered w/ Aspirin: Adverse Reactions
W/ PCI: • GI effects (abdominal pain, vomiting, dyspepsia,
Loading dose: 300-600 mg constipation); CV effects (chest pain, edema,
PO hypertension); Hematologic effects (purpura, epistaxis,
Followed by: 75 mg PO hemorrhage); Dermatologic effects (rash, pruritus);
24 hrly x 12 mth Neuromuscular effects (arthralgia, back pain); Hepatic
W/ fibrinolytic therapy: effects (LFT abnormalities)
Loading dose <75 yr: Special Instructions
300 mg PO • Contraindicated in patients w/ active bleeding
Followed by: 75 mg PO • Concurrent use of drugs known to inhibit CYP2C19 (eg
24 hrly x 12 mth Omeprazole, Esomeprazole, Cimetidine, Fluconazole,
No loading dose for >75 yr Ketoconazole, Voriconazole, Etravirine, Felbamate,
Fluoxetine, Fluvoxamine & Ticlopidine) should be
avoided
- Separating the time of administration between the

drugs does not reduce the chance of interaction
• If possible discontinue use 7 days prior to surgery
• Use w/caution in patients w/ liver impairment
1Combinations of Aspirin/Glycine & Aspirin/Clopidogrel are available.

B224
Dosage Guidelines

Drug Dosage Remarks
Prasugrel Co-administered w/ Aspirin: Adverse Reactions
Loading dose: • GI effects (N/V, diarrhea); Dermatologic effect (rash);
60 mg PO followed by Hepatic effects (elevated LFT, rarely hepatitis &
Maintenance dose: cholestatic jaundice); Hematologic effects (neutropenia,
<60 kg: 5 mg PO 24 hrly x thrombotic thrombocytopenic purpura, agranulocytosis,
12 mth hemorrhage)
≥60 kg: 10 mg PO 24 hrly x Special Instructions
12 mth • Contraindicated in patients w/ active pathologic bleeding
& hemorrhagic diathesis, patients w/ history of stroke or
TIA & in severe hepatic impairment
• Use w/ caution in patients w/ renal & moderate hepatic
impairment
• Use w/ caution when combining w/ Warfarin, Heparin,
thrombolytics, NSAIDs & other drugs that increase the
risk of bleeding
• Consider discontinuation of Prasugrel 7 days prior to
surgery
Ticagrelor Co-administered w/ Aspirin: Adverse Reactions
Single loading dose: 180 mg • Hematologic effect (bleeding, epistaxis); Resp effect
PO followed by (dyspnea); CNS effects (headache, dizziness, vertigo); GI
Maintenance dose: 90 mg PO effects (abdominal pain, N/V, constipation, diarrhea);
12 hrly x 12 mth Metabolic effect (hyperuricemia); Dermatologic effects
When an extended treatment (rash, pruritus); Other effect (post-procedural
is required for patients w/ a hemorrhage)
history of MI of at least 1 yr & Special Instructions
a high risk of an • Contraindicated in patients w/ active pathological
atherothrombotic event: bleeding, intracranial hemorrhage history, known allergy,
60 mg PO 12 hrly or severe hepatic impairment
• Use w/ caution in patients w/ increased risk for bradycardia,
moderate hepatic impairment

B225
Dosage Guidelines
BETA-BLOCKERS
Drug Dosage Remarks
Atenolol Start within 12 hr of onset of chest pain: Adverse Reactions
1st dose: 5-10 mg IV at 1 mg/min • CNS effects (fatigue, depression,
2nd dose: 50 mg PO after 15 min or 5 mg IV after dizziness, confusion, sleep
10 min followed by 50 mg PO, 10 min after the disturbances); CV effects (heart failure,
2nd IV dose heart block, coldness of extremities,
Subsequent dose: 50 mg PO after 12 hr followed by: male impotence); Resp effects
Maintenance dose: 100 mg PO 24 hrly or divided (bronchospasm in susceptible patients
12 hrly & drugs w/ beta1 selectivity should be
used w/ caution in these patients); GI
Bisoprolol 1.25 mg PO 24 hrly effects (N/V, diarrhea, constipation);
May increase to 2.5 mg after a wk if tolerated then Metabolic effects (can produce
increase gradually at 1-4 wk intervals hyper- or hypoglycemia, changes in
Max dose: 10 mg PO 24 hrly serum cholesterol & triglycerides)
Carvedilol LV dysfunction after MI: Special Instructions
Initial dose: 6.25 mg PO 12 hrly, may be increased • Monitor HR, BP & ECG during IV
after 3-10 days, if tolerated, to 12.5 mg PO 12 hrly administration of Atenolol & Metoprolol
Max dose: 25 mg PO 12 hrly • Contraindicated in severe bradycardia,
SBP <100 mmHg, preexisting high
Labetalol Hypertensive episodes following MI: degree of AV block, sick sinus
Infusion started at 15 mg/hr & gradually increased syndrome & severe, unstable LV
to max of 120 mg/hr, depending on control of BP failure, pulmonary congestion w/
Metoprolol Start within 12 hr of onset of chest pain: crackles beyond the bases, signs of
5 mg IV over 2 min peripheral hypoperfusion
May repeat giving up to total 15 mg IV at 2-min • Use w/ caution in patients w/
intervals bronchospasm, asthma or obstructive
airway diseases, 1st-degree block,
If tolerated, follow after 15 min w/ 50 mg PO depression, peripheral vascular disease
6 hrly x 48 hr & patients on Insulin
Maintenance dose: 100 mg PO 12 hrly • Beta-blockers may mask the
If patients do not tolerate 15 mg IV, give oral dose symptoms of hyperthyroidism & of
when their condition allows using a lower dose hypoglycemia & may aggravate
Late treatment (>12 hr after onset of chest pain): psoriasis
Maintenance dose: • Patients on long-term treatment
200 mg/day PO divided 12 hrly or 6 hrly should not discontinue abruptly;
Propranolol Late treatment (starting 5-21 days after MI): should discontinue gradually over
40 mg PO 6 hrly x 2-3 days followed by: 80 mg PO 1-2 wk
12 hrly or 180-240 mg/day PO in divided doses

B226
Dosage Guidelines
GLYCOPROTEIN IIB/IIIA INHIBITORS

Drug Dosage Remarks
Abciximab 250 mcg/kg as IV bolus Adverse Reactions
(over 1 min) • Hematologic effects (bleeding, thrombocytopenia); GI effects
Followed by 0.125 mcg/ (N/V); CV effects (hypotension, bradycardia, etc); Other effects
kg/min as a continuous (pain in the extremities, peripheral edema) & hypersensitivity
IV infusion reactions; CNS effects (headache, confusion, dizziness,
Max dose: 10 mcg/min abnormal vision, dysphonia, fever)
For the prevention of Special Instructions
ischemic cardiac • Contraindicated in patients w/ active bleeding, recent (<6 wk)
complications related GI or GU bleeding of clinical significance, history of CVA
to PCI: Start the bolus within the past 2 yr or CVA w/ neurologic deficit, bleeding
dose 10-60 min prior to diathesis, thrombocytopenia, anticoagulant within past 7 days
the intervention unless prothrombin time (PT) ≤1.2, recent (<6 wk) recent
followed by the surgery or trauma, intracranial neoplasm, arteriovenous
infusion for 12 hr malformation, aneurysm, severe hypertension, history of
vasculitis, use of IV dextran before percutaneous transluminal
coronary angioplasty (PTCA) or intent to use IV dextran, severe
renal or hepatic impairment
• Use w/ caution in patients <75 kg, age >65 yr, history of GI
disease & those receiving thrombolytics
• Monitor platelet counts prior to therapy, 2-4 hr after bolus & at
24 hr
Eptifibatide STEMI patients who Adverse Reactions
will undergo primary • Hematologic effects (bleeding, thrombocytopenia); CV effect
PCI: (hypotension); Hypersensitivity reactions (anaphylaxis, rash,
180 mcg/kg IV bolus urticaria)
over 1-2 min followed Special Instructions
by 2 mcg/kg/min • Contraindicated in patients w/ active bleeding (except
continuous infusion for menstrual bleeding), or active abnormal bleeding within the last
18-24 hr 30 days, history of stroke within last 30 days, history of
Give 2nd IV bolus of hemorrhagic stroke, major surgery within last 6 wk, history of
180 mcg/kg10 min after bleeding diathesis, thrombocytopenia, PT >1.2 or international
1st IV bolus normalized ratio (INR) ≥2, severe hypertension, major trauma,
If CABG is to be severe renal impairment
performed:
• Use w/ caution in patients w/ moderate renal impairment,
Discontinue prior to hepatic dysfunction
procedure

B227
Dosage Guidelines
GLYCOPROTEIN IIB/IIIA INHIBITORS (CONT’D)

Drug Dosage Remarks
Tirofiban W/ primary PCI: Adverse Reactions
Loading dose: • Hematologic effects (bleeding, thrombocytopenia); GI
25 mcg/kg IV bolus for effect (nausea); Dermatologic effect (rash); Other effects
3 min (headache, dizziness, fever & chills, bradycardia, pelvic pain)
Followed by 0.15 mcg/kg/ Special Instructions
min IV infusion x 12-24 hr • Contraindicated in patients w/ active bleeding, history of
Max duration: 48 hr intracranial hemorrhage, intracranial neoplasm,
Patients w/ CrCl <30 mL/ arteriovenous malformation or aneurysm, major surgery
min: Reduce infusion by 50% or trauma within the last mth, history of aortic
dissection, severe uncontrolled hypertension, acute
pericarditis, hemorrhagic retinopathy, anemia, serious
hepatic impairment
• Use w/ caution in patients w/ recent bleeding (<1 yr),
known coagulopathy, platelet disorder or history of
thrombocytopenia, low platelet count, history of
cerebrovascular disease (<1 yr), recent epidural
procedure, severe CHF, cardiogenic shock
• Use w/ caution in patients w/ severe renal impairment
(Cr clearance <30 mL/min)
• Monitor platelet count, hemoglobin, hematocrit prior to
treatment, within 6 hr following bolus or loading dose &
daily until completed
NITRATES (IV)
Drug Dosage Remarks
Glyceryl Initial dose: 5 mcg/min IV Adverse Reactions
trinitrate infusion • IV administration (especially if given too rapidly): May cause
(Nitroglycerin, Increase by 5 mcg/min every CV effects (severe hypotension, retrosternal discomfort,
GTN, NTG) 3-5 min up to 20 mcg/min palpitations); GI effects (nausea & retching, abdominal pain);
until some response is noted CNS effects (apprehension, restlessness, muscle twitching,
If there is still no response syncope); Other effect (diaphoresis); Prolonged administra-
at 20 mcg/min: May increase tion has been associated w/ methemoglobinemia
at increments of 10-20 mcg/ • Nitrate tolerance usually develops w/ long-term use & dosing
min every 3-5 min up to w/ adequate nitrate-free interval is recommended

400 mcg/min Special Instructions
Usual dose: 10-200 mcg/min • Avoid in patients w/ severe hypotension, hypovolemia,
Max dose: 400 mcg/min marked anemia, heart failure due to obstruction or raised
ICP due to head trauma or hemorrhage
Isosorbide 2-12 mg/hr IV infusion after • Use caution when there is a fall of SBP <110 mmHg in
dinitrate dilution normotensive patients & fall of MAP >25% in
Max dose: 20 mg/hr IV hypertensive patients
Percutaneous transluminal • Use w/ caution in patients w/ severe renal or hepatic dysfunc-
coronary angioplasty: 1 mg tion, hypothyroidism, malnutrition or hypothermia
IV bolus before balloon - Use w/ caution in inferior wall MI/post-MI
inflation • Close monitoring of HR & BP is necessary during IV
Max dose: 5 mg within infusion
30 min • Do not administer to patients who have taken
Only those approved for phosphodiesterase inhibitors within the past 24 hr
intracoronary use should be • The plastic equipment used for administration may absorb
given GTN & dosing may need to be adjusted

B228
Dosage Guidelines

Available
Drug Dosage Remarks
Strength
Glyceryl 400, 500 mcg Acute anginal attack: Adverse Reactions
trinitrate sublingual tab 300-600 mcg sublingual every • CNS effects (headache,
(Nitroglycerin, 3-5 min until cessation of pain lightheadedness, dizziness,
GTN, NTG) or side effects occur syncope); rarely CV effects
Max dose: 3 doses within (bradycardia, hypotension); GI
15 min effects (N/V, bowel incontinence,
Prophylaxis: 400-600 mcg xerostomia)
sublingual 5-10 min prior to Special Instructions
activity • Avoid in patients w/ severe
400 mcg/dose Acute anginal attack: hypotension, hypovolemia,
sublingual 1-2 sprays (400-800 mcg) marked anemia, heart failure due
spray sublingual every 5 min until to obstruction or raised
cessation of pain or side effects intracranial pressure due to head
occur trauma or hemorrhage
Max dose: 3 doses within • Use w/ caution in patients w/
15 min severe renal or hepatic
Prophylaxis: 1 spray dysfunction, hypothyroidism,
sublingual 5-10 min prior to malnutrition or hypothermia
activity • Co-administration w/
phosphodiesterase inhibitors (eg
500 mcg Acute anginal attack: Sildenafil) is contraindicated
buccal tab 2-5 mg 8 hrly, placed between within 24-hr interval after taking
gum & upper lip a nitrate preparation
If accidentally swallowed, place Acute attacks:
another tab in buccal cavity
• Instruct patient to sit down & use
Isosorbide 5, 10 mg Acute anginal attack: medication at 1st sign of angina
dinitrate sublingual tab 2.5-10 mg sublingual every attack
5-10 min until cessation of • Patient should be made aware that
pain or side effects occur dose may be repeated in 5-10 min
Max dose: 3 doses within w/ max of 3 doses given
15-30 min • Patient should seek emergency
Prophylaxis: 2.5-10 mg medical treatment if pain does not
sublingual prior to activity subside
1.25 mg/dose Acute anginal attack:
spray 1-3 sprays (1.25-3.75 mg)
sublingual at 30-sec interval
between sprays. Do not inhale
medication
Prophylaxis: 1-3 sprays
(1.25-3.75 mg) sublingual prior
to activity at 30-sec interval
between sprays. Do not inhale
medication

B229
Dosage Guidelines
OPIOID (IV)
Drug Dosage Remarks
Morphine Initial dose: 2-4 mg IV Adverse Reactions
followed by 2-8 mg IV every • GI effects (N/V, constipation); CV effects (hypotension,
5-15 min, if needed bradycardia); Resp effect (resp depression); CNS effects
or (drowsiness, confusion, changes in mood)
Initial dose: 1-5 mg IV • Diamorphine may cause less nausea & hypotension
followed by 1-5 mg IV every Special Instructions
5-30 min, if needed • Avoid IM inj
• Anti-emetics may be administered concurrently w/
opioids
• If Morphine-induced resp depression occurs, Naloxone
IV can be administered
• Contraindicated in resp depression, obstructive airways
disease
• Use w/ caution in acute alcoholism, convulsive
disorders, head injuries & if intracranial pressure is
raised, patients w/ hypothyroidism, adrenocortical
insufficiency, asthma, renal or hepatic impairment,
prostatic hyperplasia, hypotension, shock, inflammatory
or obstructive bowel disorders or myasthenia gravis
THROMBOLYTIC AGENTS (IV)

Drug Dosage Remarks
Fibrin-Nonspecific Agents
Anistreplase 30 u IV over 4-5 min as a Adverse Reactions
single dose at onset of • Hematologic effects (hemorrhage especially from puncture
symptoms sites, severe internal bleeding, intracranial hemorrhage);
Allergic reactions (rashes, flushing, urticaria & rarely
anaphylactic & serum sickness-like symptoms); Other
effects (fever, chills w/ back & abdominal pain); GI effects
(N/V); Guillain-Barre syndrome may occur
• Infusion may be associated w/ hypotension (both direct
& as a result of reperfusion), bradycardia & arrhythmias

Streptokinase Short term: 1.5 MU in may occur because of reperfusion
100 mL of 5% dextrose or
• Break-up of clots may occasionally cause emboli elsewhere
0.9% saline given by IV
infusion over 30-60 min Special Instructions
Administer UFH as • See page 6 of this management chart for specific
ancillary to thrombolytic inclusion, warnings & contraindications
therapy: • Anti-streptokinase antibodies are formed after about
UFH: 60 units/kg IV bolus 5 days after Streptokinase use
(max dose: 4,000 units), - These antibodies may cause resistance or
followed by 12 units/kg/hr IV hypersensitivity to subsequent doses of Streptokinase
infusion - Recommend not to administer Streptokinase
5 days-12 mth after 1st administration (alternative
thrombolytic not including Anistreplase may be used)
• Anistreplase appears to be antigenic & may be
neutralized by Streptokinase antibodies

B230
Dosage Guidelines
THROMBOLYTIC AGENTS (IV) (CONT’D)

Drug Dosage Remarks
Fibrin-Specific Agents
Alteplase Initiated within 6 hr of symptom onset: Adverse Reactions
(rt-PA) <65 kg: 15 mg IV bolus • Hematologic effects
Followed by: 0.75 mg/kg IV over 30 min (not exceeding (hemorrhage especially
50 mg) then 0.5 mg/kg IV over 60 min (not exceeding from puncture sites,
35 mg) severe internal bleeding,
≥65 kg: 15 mg IV bolus intracranial hemorrhage);
Other effects (fever, chills
Followed by: 50 mg IV over 30 min then 35 mg IV over 60 w/ back & abdominal
min (total 100 mg over 90 min) pain); GI effects (N/V)
Initiated 6-12 hr after symptom onset: • Rarely: Allergic reactions
<65 kg: 1.5 mg/kg body wt (max total dose) (rashes, flushing, urticaria
≥65 kg: 10 mg IV bolus & rarely anaphylactic &
Followed by: 50 mg IV infusion over 60 min then 4 serum sickness-like
infusions each of 10 mg IV over 30 min (total 100 mg over symptoms)
3 hr) • Infusion may be
Max dose: 1.5 mg/kg in patients <65 kg (100 mg) associated w/ hypotension
Administer UFH as ancillary to thrombolytic therapy: (both direct & as a result
of reperfusion),
60 u/kg IV bolus (max dose: 4000 u) followed by:
bradycardia & arrhythmias
12 u/kg/hr IV infusion (max dose: 1000 u/hr) x 48 hr may occur because of
Adjust to maintain target PTT: 50-70 sec reperfusion
Reteplase 10 u IV bolus over ≤2 min x 2 doses given 30 min apart • Break-up of clots may
(r-PA) Administer UFH as ancillary to thrombolytic therapy: occasionally cause emboli
elsewhere hence the need
60 u/kg IV bolus (max dose: 4000 u)
for Heparin prophylaxis
Followed by:
12 u/kg/hr IV infusion (max dose: 1000 u/hr) x 48 hr
• See page 6 of this
Adjust to maintain target PTT: 50-70 sec management chart for
Tenecteplase Give as single IV bolus over 5-10 sec as follows: specific inclusion,
(TNK-tPA) <60 kg: 30 mg (6000 u) warnings &
contraindications
60 to <70 kg: 35 mg (7000 u)
70 to <80 kg: 40 mg (8000 u)
80 to <90 kg: 45 mg (9000 u)
≥90 kg: 50 mg (10,000 u)
Max dose: 50 mg (10,000 u)
Administer UFH as ancillary to thrombolytic therapy:
60 u/kg IV bolus (max dose: 4000 u)
Followed by:
12 u/kg/hr IV infusion (max dose: 1000 u/hr) x 48 hr
Adjust to maintain target PTT: 50-70 sec

B231
Venous Thromboembolism -
Management (1 of 21)
DEEP VEIN 1
THROMBOSIS Patient presents w/ symptoms suggestive of DVT
(DVT)
2
DIAGNOSIS
What is the clinical pretest
probability?
Low (unlikely)
clinical pretest
probability Moderate or high
(likely) clinical
pretest probability
Is
Is duplex
D-dimer1,2 venous
Positive ultrasonography (US)2 Positive
positive or
negative? positive or
negative?
MANAGEMENT
Negative A Non-pharmacological therapy
Negative Patient education
Low (unlikely) clinical
pretest probability • Bed rest & leg elevation
• Graduated elastic compression
stockings (GECS)
3 B Parenteral anticoagulants
• Low-molecular-weight
ALTERNATIVE Heparin (LMWH), or
Moderate or high (likely)
DIAGNOSIS clinical pretest probability • Unfractionated Heparin (UFH)
(Exclude DVT) • Fondaparinux
C Oral anticoagulants
• Non-vitamin K oral
anticoagulants (NOACs)
• Warfarin
F Thrombolysis
FOLLOW-UP STUDIES • Only in massive DVT
• Repeat US in 1 week G Invasive procedures
Negative • Venography (magnetic Positive • Thrombectomy
resonance venography if • Inferior vena cava (IVC) filters
available) when appropriate
D Follow-up
• Oral anticoagulant
1D-dimer may be used for excluding DVT in a moderate or intermediate pretest probability population if prevalence is approximately ≤15%.
2Interim therapeutic anticoagulation may be given while awaiting test result; use an anticoagulant that can be continued if DVT is
confirmed.
B232
Venous Thromboembolism - Management (2 of 21)
VENOUS THROMBOEMBOLISM (VTE)

• Most commonly manifested as pulmonary embolism (PE) & deep venous thrombosis (DVT), & is associated
w/ significant morbidity & mortality
- ⅓ of patients present w/ symptoms of PE & ⅔ w/ DVT
- Also manifests as superficial vein thrombosis (SVT), a less severe form of DVT
• One of the most common life-threatening cardiovascular diseases (CVD) in the United States & w/ increasing
incidence & mortality rates in Asia
• All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of VTE &
bleeding before starting prophylaxis of VTE
- Studies show that appropriate VTE prophylaxis should be given to surgical patients in Asia who are at risk
for VTE
Pathogenesis
• Virchow’s triad theorizes 3 factors contributing to the development of VTE: Hypercoagulability, endothelial
damage, & stasis
• Hypercoagulability has been associated w/ factor V Leiden mutation & prothrombin gene mutation
- Cancer also produces a hypercoagulable state due to the procoagulant activity produced by malignant cells
& also secondary to effects of chemotherapeutic agents
• Major contributing risk factors include history of trauma, surgical procedures, spinal cord injury, long bone
fractures, & previous VTE
Risk Factors
Transient or Reversible Provoking
• Surgery within the past 4 weeks (eg hip or knee replacement)
• Major trauma
• Immobilization for at least 3 days
• Bedridden for ≥3 days
• Estrogen therapy
• Pregnancy/postpartum
• Cesarean section
• Lengthy travel, eg airline flight >8 hours
Chronic or Persistent Provoking
• Active cancer
• Active autoimmune disease, eg antiphospholipid antibody syndrome, rheumatoid arthritis
• Chronic infections or immobility, eg spinal cord injury
• Chronic inflammatory states, eg inflammatory bowel disease
Other Risk Factors
• Increasing age, male sex
• Past medical history or family history of VTE
• Lower limb fracture
• Myocardial infarction (MI) or hospitalization for atrial flutter/fibrillation or heart failure (HF) within the past
3 months
• Congestive HF or respiratory failure
• Obesity
• Varicose veins
• Blood transfusion & erythropoiesis-stimulating agents
1 DEEP VEIN THROMBOSIS (DVT)

• A frequent manifestation of VTE in which there is a blood clot blocking a deep vein
- Popliteal, femoral or iliac vein thrombus: Proximal lower extremity DVT
- Thrombus below the popliteal vein not extending to the proximal veins: Isolated distal DVT
• Patients are generally asymptomatic w/ a calf DVT but becomes symptomatic w/ proximal extension of the
DVT & venous outflow obstruction
Signs & Symptoms Suggestive of DVT
• Localized tenderness along the distribution of the deep venous system
• Unilateral or entire leg is swollen
• Calf swelling >3 cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity)
VTE - MANAGEMENT
• Pitting edema is greater in the symptomatic leg

• Collateral superficial veins (non-varicose)
• Erythema
• Warmth
• Superficial thrombophlebitis w/ a palpable cord over a superficial vein
• Phlegmasia cerulea dolens (blue leg) - deoxygenated hemoglobin in the stagnant veins causes a cyanotic hue
in the leg
• Phlegmasia alba dolens (pale leg) - pallor in the edematous legs because the interstitial tissue pressure has
exceeded capillary perfusion pressure
B233
2 DIAGNOSIS
Clinical findings are important to the diagnosis of DVT but are poor predictors of the presence or
severity of thrombosis
• Pretest probability is needed to guide the diagnostic process
WELLS SCALE OF CLINICAL PRETEST PROBABILITY FOR DVT

Pretest Total
Clinical Features Points Probability Points
Entire leg swollen 1.0 High risk ≥3
Calf swollen by >3 cm compared to the asymptomatic side (measured 1.0 Moderate risk 1-2
10 cm below tibial tuberosity) Low risk ≤0
Localized tenderness along the deep venous system distribution 1.0
Pitting edema (greater in the symptomatic leg) 1.0 If both legs are symptomatic, score
Collateral superficial veins (non-varicose) 1.0 the more severe side
Immobilization for ≥3 days or major surgery within 12 weeks 1.0
Paralysis, paresis, recent plaster immobilization of lower extremity 1.0
Previously documented DVT 1.0 Simplified version*:
Active cancer (ongoing treatment within the last 6 months or 1.0 Likely ≥2
current palliative therapy) Unlikely <2
Alternative diagnosis as likely or greater than that of DVT -2.0
Reference: Institute for Clinical Systems Improvement. Health care guideline: venous thromboembolism diagnosis and treat-
ment. 13th ed. Jan 2013.
*National Institute for Health and Care Excellence (NICE). Venous thromboembolic diseases: diagnosis, management and
thrombophilia testing. https://www.nice.org.uk. 26 Mar 2020.
Diagnostic Tests
• Baseline blood tests when initiating anticoagulation treatment includes a complete blood count (CBC), renal &
hepatic function assessment, prothrombin time (PT) & activated partial thromboplastin time (aPTT)
D-dimer Level by ELISA Assay
• A highly sensitive but nonspecific screening test for the presence of VTE
- D-dimer levels may also be elevated in patients w/ MI, sepsis, cancer, inflammation, infection, necrosis,
trauma, pregnancy, etc
- Therefore, high concentration of D-dimer has a poor positive predictive value for DVT & cannot be used to
rule in the disease
• Normal D-dimer level by ELISA assay (<500 ng/mL) has a high negative predictive value & is useful to rule out
VTE thus reducing the need for imaging when used in conjunction w/ clinical probability, plethysmography, or US
- Patients w/ a low clinical pretest probability of DVT & a negative D-dimer assay are considered to have no
DVT or have a very low risk of subsequent DVT & can be followed up clinically without further testing
unless new or progressive symptoms develop
• This is most useful in ED patients, in ambulatory care settings & in patients w/ recent onset of symptoms who
are not currently taking anticoagulants
- Can be used after a negative duplex US to determine the need for further radiologic evaluation
- In elderly or inpatients, the D-dimer retains a high negative predictive value but is normal in <10% of patients
& therefore is not useful in these patients
Duplex Venous Ultrasonography (DUS)
• B-mode, (eg 2D) imaging & pulse-wave Doppler interrogation
• Primary radiologic device for the evaluation of proximal DVT
- Most often used non-invasive test to diagnose DVT in patients w/ moderate or high clinical pretest probability
- Has a very high sensitivity & specificity for diagnosing proximal DVT in symptomatic patients, but less
favorable results for calf vein & asymptomatic DVT
- The primary diagnostic criteria to establish the presence of DVT by US is incomplete vein compressibility
- Proximal & distal compression ultrasound for DVT has 90.3% sensitivity & 97.8% specificity
• Combined use of clinical pretest probability & duplex US (w/ compression) is effective in confirming or
excluding the diagnosis of DVT
- In patients w/ clinical suspicion of DVT, positive D-dimer & negative US, consider repeat US for suspected
calf thrombosis or venography for suspected proximal thrombosis in 3-7 days
VTE - MANAGEMENT
B234
Duplex Venous Ultrasonography (DUS) (Cont’d)
• In patients w/ negative computed tomographic pulmonary angiography (CTPA) results & positive D-dimer &
a PE likely clinical probability, further evaluation w/ DUS should be used to improve clinical likelihood of
diagnosing disease & avoid more invasive testing
- A positive result confirms the diagnosis of DVT & requires treatment regardless of the presence or absence
of PE
- For a negative result, incorporation of clinical pretest probability can improve diagnostic accuracy & poten-
tially avoid unnecessary pulmonary angiography
Contrast Venography
• The gold standard for establishing the diagnosis of DVT
- Offers precise detail of the venous anatomy & the ability to reliably exclude thrombosis in the calf
- Can help distinguish between old & new clots
• Excellent for calf veins, but it is an invasive procedure, not always technically possible & carries a small risk
of an allergic reaction/venous thrombosis
- Other disadvantages include cost, patient discomfort, significant resource use, availability, requirement for
foot vein cannulation, IV contrast use & possibility of secondary thrombi
- In some countries, its use has been supplanted by venous US
- Generally reserved for difficult diagnostic cases
Magnetic Resonance Imaging (MRI)
• Provides morphological & functional information about lung perfusion & right heart function but compared
to CT scan, MRI needs improvement in the image quality
• Useful in patients w/ suspected thrombosis of the superior & inferior vena cava or pelvic veins; should be
deferred in patients w/ suspected first lower extremity DVT
• Has a similar diagnostic accuracy to that of US for assessing proximal DVT
Plethysmography
• Computerized Strain Gauge Plethysmography
- Rapid & easy to perform
- Has shown a sensitivity of 90% for proximal DVT (popliteal, femoral, or iliac vein) & 66% for distal (calf vein)
DVT
• Impedance Plethysmography (IPG)
- Normal finding w/ serial IPG is associated w/ a low risk of clinically important PE (<1%) or recurrent venous
thrombosis (2%)
- Serial testing w/ IPG for 10-14 days appears to be effective for identifying patients w/ extending calf DVT
Spiral Computed Tomography (sCT)
• Has shown promise for the diagnosis of DVT & other soft tissue diseases in patients w/ leg swelling
• Visualizes proximal obstructions & common, superficial & deep femoral veins
Recommended Diagnostic Tests based on Clinical Pretest Probability Result
• Low pretest probability: D-dimer, DUS w/ compression, venography, whole-leg US
• Moderate pretest probability: D-dimer, proximal DUS w/ compression, venography, whole-leg US
• High pretest probability: Proximal DUS w/ compression, whole-leg US, venography
• Since pain & swelling are common presenting complaints, DVT must be differentiated from other causes
including the following:
- Muscle strain, rupture or tear
- Leg swelling in paralyzed leg
- Lymphangitis, lymphedema
- Cellulitis
- Ruptured popliteal cyst (Baker’s cyst)
VTE - MANAGEMENT
- Venous insufficiency
B235
PULMONARY 4
EMBOLISM (PE) Patient presents w/ signs &
symptoms suggestive of PE
5
Yes
EVALUATION TREATMENT
Massive/sub-
Is massive/sub-massive massive PE See next page
PE suspected?
No
Non-massive PE
6
Low1 or
ASSESSMENT High (likely)
intermediate
What is the clinical clinical
(unlikely)
pretest probability of pretest
clinical pretest
non-massive probability
probability
PE?
6
6 ASSESSMENT
ASSESSMENT Positive Is VQ scan2,4 or CT
Is D-dimer4 positive pulmonary angiography
or negative? (CTPA)3,4 positive
for PE?
Negative
No Yes
7 B Parenteral anticoagulants
• Low-molecular-weight Heparin (LMWH), or
ALTERNATIVE DIAGNOSIS
• Unfractionated Heparin (UFH), or
• Fondaparinux
C NOACs or Warfarin
D Follow-up
VTE - MANAGEMENT
1Pulmonary Embolism Rule-Out Criteria (PERC) may be used to determine the need for testing for D-dimer in patients w/ a low
probability of PE presenting in the emergency department (ED).
2Perform VQ scan if available & feasible. If not, perform CTPA. If VQ scan is non-diagnostic, perform CTPA or bilateral duplex
ultrasound of lower limbs. If positive, give anticoagulation.
3Perform CTPA in patients w/ a high probability of PE. If negative, D-dimer, VQ scan or duplex ultrasound may be performed.
4Interim therapeutic anticoagulation may be given while awaiting test result; use an anticoagulant that can be continued if PE is confirmed.
B236
SUSPECTED MASSIVE/SUB-MASSIVE PE
E Prompt management of clinical instability
5
Yes No
Massive
EVALUATION Sub-
PE Is massive PE massive PE
confirmed?
B Bolus of UFH
• Thrombolysis may
5 be considered
EVALUATION
Absolute contraindications
to thrombolysis?
No Yes
F Thrombolysis G Invasive procedures

• Preferred agent: Alteplase • Pulmonary embolectomy
• Alternatives: Streptokinase • Percutaneous catheter-
or Urokinase directed treatment
4 PULMONARY EMBOLISM (PE)

• Blockage of the blood vessels in the lungs usually due to blood clots from the veins, especially the veins in the
legs & pelvis
• Subsegmental PE is PE which does not involve the proximal pulmonary arteries
Typical Signs & Symptoms
• Suspicion of PE is usually raised by the clinical symptoms
- Clinical findings are nonspecific & should not be the only criteria to diagnose PE
• Dyspnea, pleuritic chest pain, syncope & tachypnea (respiratory rate ≥20/minute) occur in most cases of PE
- Dyspnea is the most frequent symptom, while tachypnea is its most frequent sign
- Other signs & symptoms that may be present: Tachycardia (heart rate >100/minute), cough & hemoptysis,
fever, diaphoresis, nonpleuritic chest pain, apprehension, rales, increasing pulmonic component of the 2nd
heart sound, wheezing, hypotension, cyanosis, pleural rub, raised jugular venous pressure
- PE should be suspected in cases of postoperative hypoxemia
Pleuritic Chest Pain
• Pleuritic chest pain w/ or without dyspnea is one of the most frequent presentations of PE
- May suggest a small embolism located distally near the pleura that also causes pleural irritation
Isolated Dyspnea
• Isolated dyspnea may occur suddenly or progressively (over several weeks)
- Usually due to a more central PE (not affecting the pleura)
- May be associated w/ substernal angina-like chest pain that probably is representing right ventricular (RV)
VTE - MANAGEMENT
ischemia
- Worsening dyspnea may be the only symptom that indicates PE in patients w/ preexisting HF or pulmonary disease
Syncope or Shock
• Syncope or shock is the hallmark sign of central PE & usually results in severe hemodynamic repercussions
- Signs of hemodynamic compromise & reduced heart flow are also usually present (eg systemic arterial
hypotension, oliguria, cold extremities &/or clinical signs of acute right HF)
B237
5 EVALUATION
Clinical Evaluation
• A reasonable clinical suspicion is required to avoid missing the diagnosis of PE
• Evaluating the likelihood of PE in an individual patient according to the clinical presentation is of utmost
importance in the interpretation of diagnostic test results & the selection of an appropriate diagnostic
strategy
- A bedside transthoracic echocardiogram may be done in patients who are hemodynamically unstable to
differentiate suspected high-risk PE from other acute life-threatening conditions
- Patients should also be evaluated for risk factors for VTE
• It is recommended to perform initial risk stratification in hemodynamically unstable patients w/ suspected
or confirmed PE to identify those w/ a high risk of early mortality
• Acute PE severity may be stratified using validated scores from combined clinical, laboratory & imaging
prognostic factors in patients who are hemodynamically stable
- The Pulmonary Embolism Severity Index (PESI) identifies the patient's overall mortality risk using PE severity
& comorbidity
- A score of ≥1 indicates a 30-day mortality risk of 10.9% in the simplified version of PESI
Massive PE
• Accounts for 5-10% of cases
Signs & Symptoms
• Dyspnea is usually the prime symptom & systemic arterial hypotension that requires pressor support is the
predominant sign
- Persistent hypotension is defined as a systolic BP (SBP) of <90 mmHg or a pressure drop of at least 40 mmHg
from baseline for at least 15 minutes (or needing inotropic support) not caused by new-onset arrhythmia,
hypovolemia or sepsis; or absence of pulse, or sustained heart rate <40 beats/minute (bpm) w/ signs or
symptoms of shock
• Syncope & altered mentation
• Renal insufficiency, hepatic dysfunction
• Severe respiratory distress or hypoxemia (eg cyanosis)
• In patients w/ suspected massive PE who are too unstable for lung imaging, RV dysfunction can usually be
found at the bedside
- Left parasternal heave, distended jugular veins & systolic murmur of tricuspid regurgitations that increases
w/ inspiration
Sub-massive PE
• Occurs in approximately 20-25% of patients
• Subgroup of non-massive PE patients who present w/ the following:
- Normal BP, normal tissue perfusion & clinical or echocardiographic evidence of RV dysfunction or myocardial
necrosis
- Elevated troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP) or BNP
Low-Risk PE
• Affects approximately 70% of patients w/ PE
• PE that presents w/ normal systemic arterial pressure & RV function, & no elevated cardiac biomarkers
• Patients w/ suspected or confirmed low-risk PE may be considered for outpatient treatment after clinical
assessment & after being determined suitable using a validated risk stratification tool
Absolute Contraindications to Thrombolysis
• Hemorrhagic stroke or stroke of unknown origin at any time
• Major trauma, surgery, or head injury in the past 3 weeks
• Ischemic stroke within the past 6 months
• CNS damage or tumors
• Severe coagulation disorders
• Active bleeding
• Known increased risk for bleeding (bleeding diathesis)
Relative Contraindications
• Transient ischemic attack within the past 6 months
• Puncture of a non-compressible vessel
• Uncontrolled severe hypertension [SBP >180 mmHg, diastolic BP (DBP) >100 mmHg]
• Neurosurgery or ophthalmologic surgery within the last 1 month
• Ischemic stroke within the last 2 months
VTE - MANAGEMENT
• GI bleeding within the last 10 days

• Active peptic ulcer disease
• Recent traumatic cardiopulmonary resuscitation (CPR)
• Pregnancy or within 1 week postpartum
• Oral anticoagulant therapy
• Advanced liver disease
B238
6 ASSESSMENT
Pretest Probability of PE
• All patients w/ possible PE should have clinical probability assessed & documented
- Clinical probability may be estimated empirically or explicitly by a prediction rule
• There are 2 frequently used pretest probabilities of PE: Geneva score (Europe) & Wells scale (Canadian
rule)
Geneva Score
• Requires arterial blood gas measurement & a chest radiograph
GENEVA CLINICAL PREDICTION RULE FOR PULMONARY EMBOLISM

Simplified Pretest Total Simplified
Clinical Features Points Version Probability Points Version
Age >65 years 1 1 Based on likelihood of PE
Active cancer 2 1 PE likely ≥6 ≥3
Fracture or surgery within the 2 1 PE less likely 0-5 0-2
past month
Heart rate According to risk groups
75-94 bpm 3 1 High ≥11 ≥5
≥95 bpm 5 2 Intermediate 4-10 2-4
Hemoptysis 2 1 Low 0-3 0-1
Previous DVT or PE 3 1
Unilateral edema & pain on 4 1
lower-limb deep venous
palpation
Unilateral pain in lower limb 3 1
Reference: 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with
the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the
European Society of Cardiology (ESC). Eur Respir J. 2019 Aug 31.
Wells Scale
• Requires that the patient has clinical features suggestive of PE (eg breathlessness, &/or tachypnea w/ or
without pleuritic chest pain &/or hemoptysis)
• Along w/ 2 other features
1. The absence of another reasonable clinical explanation
2. The presence of a major risk factor
WELLS SCALE OF CLINICAL PRETEST PROBABILITY FOR PULMONARY EMBOLISM

Simplified Pretest Total
Clinical Features Points Version* Probability Points
Clinical signs & symptoms of DVT 3.0 1 Based on likelihood of PE
Alternative diagnosis is less likely than PE 3.0 1 PE likely >4
Heart rate ≥100 bpm 1.5 1 PE less likely ≤4
Immobilization for ≥3 days or surgery within 1.5 1
the past 4 weeks According to risk groups
Previous DVT/PE 1.5 1 High >6
Hemoptysis 1.0 1 Intermediate 2-6
Malignancy (w/ treatment within the last 1.0 1 Low <2
6 months)
Simplified version*
≥2
VTE - MANAGEMENT
Likely
Unlikely <2
Reference: Institute for Clinical Systems Improvement. Health care guideline: venous thromboembolism diagnosis and treatment.
13th ed. Jan 2013.
*2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the
European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the
European Society of Cardiology (ESC). Eur Respir J. 2019 Aug 31.
B239
6 ASSESSMENT (CONT'D)
Pulmonary Embolism Rule-Out Criteria (PERC)
• Use to identify group at very low risk of PE & to determine if additional investigations for PE are warranted
• If the patient has answered yes in any of the following questions, the patient is PERC positive:
- Is the patient >49 years?
- Is the patient’s heart rate >99 bpm?
- Is the patient’s pulse oximetry reading <95% while breathing room air?
- Does the patient have hemoptysis?
- Is the patient on exogenous estrogen?
- Does the patient have prior diagnosis of VTE?
- Has the patient had surgery or trauma in the previous 4 weeks?
- Does the patient have unilateral leg swelling at the calves?
• In selected patients, PE can be ruled out without imaging tests or D-dimer if PERC is negative
Diagnostic Tests
• 1st-line diagnostic tests eg electrocardiography (ECG), chest X-ray & arterial blood gases are indicated to
assess clinical probability of PE & general condition of patient
• Lab results can be normal but some abnormal findings increase the suspicion for PE
• Baseline blood tests when initiating anticoagulation treatment includes a CBC, renal & hepatic function
assessment, PT & aPTT
Arterial Blood Gas
• Can show hypoxemia, hypocapnia & widened (A-a) O2 difference
Chest X-ray
• May demonstrate atelectasis, pleural-based infiltrates or effusions or rarely engorged central pulmonary artery
associated w/ a paucity of peripheral vessels
• Near-normal radiographic results w/ severe respiratory compromise is highly suggestive of massive PE
• Westermark sign (focal oligemia) may indicate massive central embolic occlusion
• Hampton lump, a peripheral wedge-shaped density above the diaphragm, usually signifies pulmonary infarction
ECG
• Can show right axis deviation, supraventricular arrhythmia, S1Q3T3 pattern or P-pulmonale, sinus tachycardia,
or a normal tracing
• For massive PE, ECG may show new right bundle branch block or other evidence of RV strain (eg inverted T
waves in leads V1-V4)
B-type Natriuretic Peptide (BNP) & Troponin
• Consider in a patient w/ substantial clot burden, abnormal echocardiogram or clinical findings suggestive of PE
• Elevated BNP & troponin are associated w/ RV strain & increased mortality even in the absence of hemodynamic
instability
D-Dimer
• A highly sensitive but a nonspecific screening test for the presence of PE
- Sensitivity may be decreased if the duration of VTE manifestations is >2-3 days prior to testing &/or if the
patient is on Heparin
- Best used for evaluation of outpatients in the ED
• A negative D-dimer test via any D-dimer method (SimpliRED, Vidas or MDA) reliably excludes PE in patients
w/ low clinical probability, such patients do not require imaging for VTE
• A negative result using ELISA (Vidas) or MDA methods reliably excludes PE in patients w/ intermediate probability
• A positive D-dimer requires further radiological evaluation to exclude PE adequately
- However, raised levels of D-dimer do not confirm the presence of VTE because such levels are found in
hospitalized patients, obstetrics including postpartum period, peripheral vascular disease, cancer, infection,
trauma, & many inflammatory diseases as well as increasing age
• Consider using an age-adjusted cut-off or adapting to clinical probability as an alternative to the fixed cut-off
D-dimer test level
• D-dimer measurement should not be performed in those w/ high clinical probability of PE
• Inappropriate for suspected VTE w/ recent surgery or trauma & should proceed directly to radiologic studies
eg duplex US or CTPA
Computed Tomographic Pulmonary Angiography (CTPA)
VTE - MANAGEMENT
• Recommended as the initial lung imaging modality for patients w/ suspected PE

• Increasingly used as an adjunct or alternative to other imaging modalities & is superior in specificity to
ventilation-perfusion isotope scanning
• Multidetector computed tomographic angiography (CTA) has 83% sensitivity & 96% specificity
• A positive CTPA, w/ intermediate or high clinical pretest probability, is confirmed positive for PE & no
further diagnostic testing is needed
• A normal CTPA, w/ low or intermediate clinical pretest probability, is confirmed negative for PE & no
further diagnostic testing is needed
B240
Computed Tomographic Pulmonary Angiography (CTPA) (Cont'd)
• Enables direct visualization of the pulmonary emboli & may provide information about parenchymal
abnormalities that might help to establish an alternative diagnosis
• More useful for patients w/ underlying cardiac disease, COPD or asthma
• Has a high specificity & sensitivity for central clots
• The main disadvantage of CTPA to that of conventional pulmonary angiography is that subsegmental clot
is less likely to be seen
• Patients w/ a good quality negative CTPA do not require further investigation or treatment for PE
Echocardiography
• Most useful initial test which typically shows indirect signs of acute pulmonary hypertension & RV overload
if acute PE is the cause of the hemodynamic changes
• If patient is unstable, thrombolytic treatment or surgery can be done based only on compatible echocardiography
findings
• If patient has been stabilized, a definitive diagnosis should be pursued
- Lung scan, sCT & bedside transesophageal echocardiography (TEE) are usually able to confirm diagnosis
- Normal lung scan or sCT angiogram suggests that another cause of shock should be found
• Useful for rapid triage in acutely ill patients w/ suspected massive PE
- Usually reliable to differentiate between illnesses that have radically different treatments compared to PE (eg
AMI, pericardial tamponade, infective endocarditis, aortic dissection, etc)
- May suggest/reinforce clinical suspicion of PE w/ the findings of RV overload & dysfunction in the presence
of Doppler signs of increased pulmonary arterial pressure
- May also definitively confirm diagnosis of PE by visualization of proximal pulmonary arterial thrombi
• It has not been confirmed that echocardiography can identify patients who would benefit from thrombolytic
therapy if they present without shock or hypotension
Other Diagnostic Tests
Conventional Pulmonary Angiography
• Historically considered the gold standard for the diagnosis of PE
• Limitations include requirement of expertise in performance & interpretation, it is invasive & there are associated
risks
- W/ subsegmental clot, there can be inter-observer disagreement in up to 1/3 of cases
• Angiography should be reserved for patients in whom non-invasive tests remain inconclusive or are not
available
• Use of pulmonary angiography may also depend on patient’s clinical status & necessity to obtain an absolute
diagnosis
Ventilation-Perfusion Lung Scanning (V/Q scan)
• Normal or near-normal lung scans are sufficient to exclude PE, regardless of pretest probability
• Low probability scans in combination w/ a low pretest probability make probability of PE low
• High probability scans provide the predictive power to establish diagnosis in context of reasonable suspicion
of PE
• A VQ single-photon emission computed tomography (SPECT) may also be considered for the diagnosis of PE
- Rate of non-diagnostic tests is low at <3%
Venous Ultrasonography (US)
• Most pulmonary emboli arise from the deep veins of the legs thus it is rational to search for a residual DVT
in suspected PE patients
• Normal US exam of the leg veins does not rule out PE
• US studies may have false positive or may detect residual abnormalities from past VTE
- Only definite positive studies under certain clinical circumstances (eg patient without history of VTE but
has a high clinical probability of PE) should serve as a basis for the start of therapy
• Used to improve estimation of the clinical probability of PE & avoid more invasive testing in patients w/ a
negative lung imaging study
• A compression ultrasonography (CUS) demonstrating a proximal DVT in patient suspicious for PE confirms
the diagnosis of VTE (& PE)
- If PE was confirmed using a positive proximal compression ultrasonography, consider risk assessment to
guide patient’s management
Magnetic Resonance Angiography (MRA)
• MRA appears to be promising in human & animal models
• It avoids ionizing radiation but has a poor sensitivity for subsegmental clots & limited access is likely to continue
VTE - MANAGEMENT
for several years
• For PE, conditions that need to be ruled out include the following:
- Cardiogenic shock, cardiac tamponade, aortic dissection, pneumonia, massive MI
B241
Patient Education
• Educate patients & their families about DVT/PE, especially its signs & symptoms, risk of recurrence of disease,
risk of long-term disability & about the possibility of genetic predisposition
• Explain treatment options to patients & discuss the benefits, risks & side effects of anticoagulation therapy
• Discuss lifestyle issues w/ patients
• Advise patients to drink plenty of fluids
• Lay public may not be familiar w/ PE & discussing it may assuage their emotional burden
Bed Rest & Leg Elevation
• Affected extremity should be elevated above the level of the heart until edema & tenderness subside
Early Ambulation
• Preferred over bed rest when feasible in patients w/ acute DVT
Exercise
• Encourage patients confined to a chair or bed to perform regular leg exercise
Graduated Elastic Compression Stockings (GECS)
• Provide continuous stimulation of blood flow & prevent dilation of venous system in the legs
• GECS combined w/ early ambulation does not increase pulmonary embolism & provides faster resolution of
pain & swelling
• Recommended to start at 1 month of diagnosis of proximal DVT until a minimum of 2 years to prevent post-
thrombotic syndrome
- Use graduated compression, knee-high, custom-fitted stockings w/ at least 30-40 mmHg on the affected leg
• Should be used w/ caution in patients w/ post-thrombotic syndrome
• Contraindicated in patients w/ peripheral artery disease
• Some studies show the ineffectiveness of GECS for prophylaxis & they also cause lower extremity skin damage;
thus, routine use of compression stockings is not recommended in patients w/ DVT, w/ or without an increased
risk of post-thrombotic syndrome
B PARENTERAL ANTICOAGULANTS IN THE MANAGEMENT OF DVT

& NON-MASSIVE PE
General Therapy Principles Regarding Heparin
• Anticoagulation should be administered without delay in patients w/ intermediate or high clinical probability
of PE during diagnostic workup & in low probability patients once PE is confirmed
• If PE occurs postoperatively, Heparin therapy should be started after consultation w/ surgeon & at 12-24 hours
after major surgery
- Treatment could be delayed even longer if there is any evidence of bleeding from the surgical site
• Similar initial & long-term treatment is recommended for asymptomatic DVT
• Protamine sulfate may be used for reversal of anticoagulation
Unfractionated Heparin (UFH) & Low-Molecular-Weight Heparin (LMWH)
• Both SC LMWH & IV UFH short-course treatments are recommended for objectively confirmed non-massive PE
- Either LMWH or UFH is appropriate for the initial treatment of PE
• It is not recommended to give UFH or LMWH monotherapy in patients w/ severe renal impairment (CrCl
<30 mL/min)
UFH
• IV UFH treatment in PE is well-established
• UFH should be considered:
- As a 1st-dose bolus
- For massive/sub-massive PE
- Without delay in suspected high-risk PE patients w/ hemodynamic instability
- When rapid reversal of effect may be required
• May also be given to patients w/ high bleeding risks, receiving thrombolysis, or undergoing invasive procedures
• Patients w/ confirmed PE & hemodynamic instability may be given continuous UFH infusion w/ thrombolytic
therapy
• UFH is preferred over LMWH in patients w/ severe renal failure
VTE - MANAGEMENT
• Effects: IV UFH has been proven effective in the therapy of PE & DVT
- Studies have shown a reduced mortality rate when UFH has been used to treat VTE disease
- Recurrence of VTE is unusual when UFH is infused at a rate that prolongs the aPTT >1.5-2.5 times the
control value & when adequate levels are reached within 24 hours
• IV UFH typically requires hospitalization w/ close lab monitoring & dose adjustment
• Most common complication is Heparin-induced thrombocytopenia
B242
B PARENTERAL ANTICOAGULANTS IN THE MANAGEMENT OF DVT

& NON-MASSIVE PE (CONT'D)
LMWH
• LMWH should be used whenever possible for the initial inpatient treatment of DVT rather than UFH
- LMWH is superior to UFH for the initial treatment of DVT in terms of reducing mortality & the risk for
major bleeding during the initial therapy
• LMWH is now preferred over UFH in patients w/ acute non-massive PE
- Also preferred over vitamin K antagonists (VKA)
• LMWH or Fondaparinux is recommended over UFH for the acute-phase treatment of low- or intermediate-risk PE
• A number of studies have shown that LMWH has equal efficacy to UFH in patients w/ non-massive PE
• Patients w/ symptomatic PE should initially be treated in the hospital because of decreased cardiorespiratory
reserve, complications, & for monitoring of INR to guide Warfarin therapy
• The use of LMWH is safe, effective, may shorten hospital stay & improve the quality of life for patients
- Monotherapy w/ LMWH may be used in patients w/ active cancer or established renal failure, & considered
in patients w/ liver disease & coagulopathy
- May also be given concurrently w/ a VKA for patients w/ active cancer or antiphospholipid syndrome
- Outpatient management of DVT should be extended to include stable patients w/ stable PE who have been
carefully screened for risk factors for hemorrhage
• Lab monitoring is not required except for a regular platelet count before treatment initiation & on the 5th day,
then every 2-3 days if LMWH treatment is continued
Fondaparinux
• Also a preferred initial treatment for DVT & PE
• Heparin assay (anti-factor Xa) has been used to monitor effects of Fondaparinux
• Warfarin is initiated usually within 72 hours of therapy
• Obtain a platelet count prior to the start of therapy
Duration of Therapy
• Treatment w/ UFH, LMWH, or Fondaparinux should be continued for at least 5-7 days after the initiation of
Warfarin & until therapeutic INR is stable & ≥2.0 (range: 2.0-3.0) for 2 consecutive days
C ORAL ANTICOAGULANTS IN THE MANAGEMENT OF DVT & NON-MASSIVE PE

General Therapy Principles Regarding Anticoagulant Therapy
• For patients w/ DVT or PE, primary treatment of 3 months duration is recommended
- Proximal DVT or PE provoked by major surgery or trauma that is transient: Treatment is stopped after 3 months
- Proximal DVT or PE which is unprovoked or associated w/ a non-surgical transient risk factor: Treat for
3-6 months
- Proximal DVT or PE which is recurrent unprovoked, provoked by active cancer or antiphospholipid antibody
syndrome or by a chronic risk factor: Treat w/ extended anticoagulation
- Distal DVT provoked by a transient risk factor: Treat for 6 weeks
- Distal DVT which is unprovoked or w/ persisting risk factors: Treatment is stopped after 3 months
Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)
• Eg Apixaban, Dabigatran, Edoxaban, Rivaroxaban
• Also known as direct oral anticoagulants (DOACs)
• Recommended anticoagulant agents for patients w/ leg DVT or PE during the 1st 3 months of therapy
- Preferred over VKA in eligible PE patients for the acute-phase treatment of low- or intermediate-risk PE
• Drug interactions are few, bleeding risk is low & routine monitoring is not required
• Studies suggest that NOACs have a safety advantage over conventional therapy for VTE treatment in Asian patients
• May be given to patients w/ renal impairment or active cancer
• Apixaban & Rivaroxaban are given according to the single-drug approach (monotherapy) while Dabigatran &
Edoxaban should be given after initial treatment w/ Heparin (dual therapy)
• For reversal of anticoagulation, Idarucizumab may be used for patients taking Dabigatran while Andexanet
alfa may be used for patients taking Apixaban or Rivaroxaban
- Ciraparantag is an investigational agent that can bind & inhibit factor Xa inhibitors, UFH, LMWH, &
Fondaparinux
VTE - MANAGEMENT
Apixaban
• Prior Heparin treatment is not necessary, though short courses of Heparin should be given when there is
treatment delay
Dabigatran etexilate
• Approved for the management of DVT & PE in patients who have been treated w/ parenteral anticoagulant
for 5-10 days, & to reduce risk of recurrent DVT & PE in patients who have been previously treated
B243
C ORAL ANTICOAGULANTS IN THE MANAGEMENT OF DVT & NON-MASSIVE PE (CONT'D)

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) (Cont'd)
Edoxaban
• May be used for treatment of DVT & PE in patients who have been treated w/ parenteral anticoagulant for
5-10 days
• Considered as an alternative agent to LMWH for PE patients w/ cancer (except GI cancer)
Rivaroxaban
• Initial treatment for both PE & DVT without additional anticoagulation
• A direct factor Xa inhibitor that is non-inferior to Warfarin in the management of acute VTE
• Considered as an alternative agent to LMWH for PE patients w/ cancer (except GI cancer)
Warfarin
• Warfarin is a VKA & is used to reduce the risk of VTE recurrence & complications
• Should only be started once VTE has been reliably confirmed
- Start on day 1 of Heparin therapy
• Bolus dose is not effective, therefore it requires at least 5 days to achieve its full effects
- Thus, it is recommended that Warfarin therapy overlap w/ parenteral anticoagulation at least 4-5 days until
therapeutic INR is stable & >2.0 (range: 2.0-3.0) in 2 consecutive readings
- Warfarin high loading dose (>10 mg) is not recommended as it has no clinical use & it predisposes patients
to hemorrhage at start of therapy
- Overdose may be reversed easily w/ vitamin K administration
• Warfarin overlapping w/ UFH, LMWH or dose-reduced Enoxaparin may be considered in patients w/ severe
renal impairment, established renal failure or increased risk of bleeding
• Patients w/ antiphospholipid antibody syndrome are recommended to undergo indefinite VKA treatment
D FOLLOW-UP (DVT & NON-MASSIVE PE)

• Provoked VTE w/ persistent risk factors & second episode of unprovoked VTE have the highest recurrence
rates at 1 year & 5 years after stopping anticoagulation therapy
- Other strong risk factors for recurrence include a PE, proximal DVT or a previous VTE
- A high (>8%/year) risk for long-term recurrence is seen in patients w/ active cancer, antiphospholipid antibody
syndrome, & ≥1 prior VTE episodes without a transient factor
• Patients w/ acute PE are recommended to follow up 3-6 months after acute episode
- Have a high frequency (20-50%) of symptomatic extension of thrombus &/or recurrent VTE & therefore
require long-term anticoagulant treatment
• Extended anticoagulation treatment should be considered in the following patients w/ an index PE episode:
- Have no identifiable risk factor or w/ a minor transient risk factor
- W/ a persistent risk factor other than antiphospholipid antibody syndrome
• Patients receiving extended treatment should be followed up at least annually & checked for presence of
bleeding & recurrent VTE, changes in hepatic or renal function, adherence to therapy, treatment preferences
& new drug interactions
• Consider further evaluation for PE survivors who are asymptomatic & at increased risk for chronic
thromboembolic pulmonary hypertension
• If anticoagulation treatment failure occurs, check patient's adherence to therapy, check for malabsorption or
treatment suspension for a planned procedure, increase anticoagulant dose or administration frequency or switch
to an anticoagulant w/ a different mechanism of action, & address other causes of hypercoagulability
LMWH
• Treatment option for patients w/ recurrent VTE unresponsive to VKA therapy or for those w/ breakthrough
VTE during VKA therapy
- Dose may be increased if there is treatment failure to present dose
• For patients w/ PE & cancer, LMWH is preferred over VKAs & should be used for the 1st 6 months of long-term
VTE - MANAGEMENT
anticoagulant therapy
- After which, these patients should receive oral anticoagulant therapy indefinitely or until cancer has resolved
Oral Anticoagulant
• Treatment w/ oral anticoagulant is the preferred method of long-term management of most patients w/ PE
- Adjusted doses of UFH or LMWH may be indicated for selected patients in whom oral anticoagulants are
contraindicated or impractical
B244
D FOLLOW-UP (DVT & NON-MASSIVE PE) (CONT'D)

Oral Anticoagulant (Cont'd)
• Duration of anticoagulation is dependent on the type of event & the coexistence of prolonged risk factors:
- Continue x ≥3 months: 1st event w/ transient risk factors
- Continue x ≥6 months: 1st episode, idiopathic VTE
- Continue x ≥12 months: Recurrent, idiopathic VTE or continuing risk factor
- Continue x 6-12 weeks: Symptomatic isolated calf vein thrombosis
- Consider for indefinite anticoagulation: 2nd episode of unprovoked PE, chronic risk factor, or patients w/
PE & cancer without high bleeding risk
• For patients w/ leg DVT or PE, NOACs are preferred over VKA agents for the 1st 3 months of long-term
- VKA agents are preferred over LMWH for patients w/ VTE
- For VTE patients w/ cancer, LMWH is preferred over VKA agents & NOACs are alternative agents
• For patients who need to continue on extended anticoagulant therapy, therapeutic or low-dose NOACs (eg
Apixaban or Rivaroxaban) can be given after the first 6 months & are preferred over Warfarin if without
contraindications
Warfarin
• An INR range of 2.0-3.0 is recommended for patients w/ VTE who will continue VKA therapy as extended
anticoagulation after having completed the primary treatment
Aspirin
• May be considered for the prevention of recurrent VTE in patients w/ unprovoked proximal DVT or PE who
refused continued anticoagulant therapy
• Aspirin or Sulodexide may be considered for an extended VTE prophylaxis in patients who refuse or cannot
tolerate oral anticoagulation
• For patients who sustained a VTE while taking Aspirin for primary CVD prevention or for stable coronary
artery disease, it is advised to suspend Aspirin while taking anticoagulant therapy
International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Risk
• Used to assess a confined patient’s risk for bleeding prior to initiation of therapy
• Score of ≥7 signifies increased bleeding risk
Score Medical History

4.5 Active gastric or duodenal ulcer
4 Bleeding event <3 months before consultation; thrombocytopenia (platelet count <50 x 109/L)
3.5 ≥85 years of age
2.5 Liver failure (INR >1.5); severe renal failure (GFR <30 mL/min/1.73 m2); ICU/CCU admission
2 Central venous catheter; rheumatic/autoimmune disease; current malignancy
1 40-84 years of age; male; moderate renal failure (GFR 30-59 mL/min/1.73 m2)
Risk Factors for Major Bleeding during Anticoagulation
• Age >75 years
• History of previous bleeding
• Previous noncardioembolic stroke
• Chronic hepatic & renal disease
• Concomitant antiplatelet therapy
• Poor anticoagulant control
• Suboptimal monitoring of therapy
• Comorbid illness, eg cancer, hypertension, thrombocytopenia, anemia
• Frequent falls, alcohol abuse
Monitoring during Anticoagulation Therapy
• INR should be checked at least weekly during the 1st several weeks of Warfarin therapy
• If stable, monitor every 2 weeks then every 4 weeks
• Target INR is 2.5 for most patients & 3.0 for patients w/ recurrent VTE
• Regularly monitor therapeutic levels to ensure effective anticoagulation in patients weighing <50 kg or >120 kg
VTE - MANAGEMENT
Monitoring without Anticoagulation Therapy

• Recommended for patients w/ isolated distal leg DVT & no severe symptoms or risk factors of extension (eg
inpatient status, history of VTE, active cancer, persistent provoking factor, thrombosis near proximal veins,
involvement of multiple veins, & positive D-Dimer), & those w/ subsegmental PE without proximal leg DVT
• Serial ultrasound imaging of both legs for 2 weeks is suggested for patients w/ isolated distal leg DVT without
severe symptoms or risk factors of extension
B245
E PROMPT MANAGEMENT OF CLINICAL INSTABILITY

O2 Supplementation
• May be necessary in patients w/ hypoxemia
• Hypoxemia can usually be reversed w/ nasal O2 so that mechanical ventilation is rarely necessary
Mechanical Ventilation
• May be needed temporarily in patients who appear toxic & hypoxic
• Care should be taken to limit its hemodynamic adverse effects
- Positive intrathoracic pressures induced by mechanical ventilation may reduce venous return & worsen RV failure
• Low tidal volumes of approximately 6 mL/kg body weight are recommended
Hemodynamic Support
Fluid Loading
• Fluids may be administered initially & cautiously, but other vasoactive therapy should promptly follow
• The usefulness of fluid challenge is controversial & should not exceed 500 mL over 15-30 minutes
- May be harmful when systemic hypotension is present
Adrenergic Agonists
• Should be considered for patients w/ low cardiac index & normal BP or w/ impending hypotension
• In high-risk PE patients, Dobutamine &/or Norepinephrine should be considered
Dobutamine
• Considered 1st-line agent to treat right-sided HF & cardiogenic shock
• Action: Affects vasodilatation of both systemic & pulmonary vascular beds, increases myocardial contractility
while decreasing right-sided filling pressures
Dopamine
• Has also been used for hemodynamic support in PE patients
• Use may be limited by the development of tachycardia
Epinephrine
• May be effective when shock complicates acute PE
• Action: Vasoconstrictor effect similar to Norepinephrine, inotropic effect more due to potent β1 stimulation
rather than β2 effect, accounting for improved pulmonary vascular resistance
Norepinephrine
• May be appropriate in acute massive PE when there is profound hypertension, eg cardiogenic shock
• Action: Stimulates both α-adrenergic (inducing vasoconstriction) & β1-adrenergic receptors (augmenting
cardiac contractility) resulting in improved systemic BP, cardiac output, pulmonary vascular resistance & RV
pressure
• Combination w/ other vasoactive agents eg Dobutamine needs further evaluation
Nitric Oxide Inhalation
• May be indicated in patients w/ pulmonary hypertension & a patent foramen ovale
• Effects: May improve the hemodynamic status & gas exchange in patients w/ PE
F THROMBOLYSIS IN MASSIVE/SUB-MASSIVE PE
General Therapeutic Principles
• High-risk PE patients are recommended to receive systemic thrombolytic therapy
• Patients w/ hemodynamic deterioration on anticoagulation therapy are recommended to undergo rescue
thrombolytic treatment
• Studies have shown a more rapid improvement in radiographic & hemodynamic abnormalities in acute massive PE
patients who received thrombolytic agents followed by anticoagulant agents over conventional anticoagulant agents
alone
- There were no clinically relevant outcomes for death rate or for the resolution of symptoms
• Treatment started within 48 hours of symptom onset provides the most benefit, though thrombolysis can still
be used in those who are symptomatic for 6-14 days
• Catheter-directed thrombolytic therapy may also be considered in patients w/ massive iliofemoral DVT (weigh
risk vs benefit) w/ symptoms of <14 days, limb-threatening DVT (phlegmasia cerulea dolens), good functional
status, low risk of bleeding & ≥1-year life expectancy
Massive PE
VTE - MANAGEMENT
• The use of thrombolytic therapy in PE should be individualized

- Patients w/ hemodynamically unstable PE who are at low risk of bleeding are the most appropriate candidates
• Thrombolytic therapy may also be considered in patients w/ the following:
- Compromised oxygenation
- Free-floating RV thrombus or patent foramen ovale documented by echocardiography
- Massive hemodynamically significant PE without systemic hypotension or profound hypoxemia
B246
F THROMBOLYSIS IN MASSIVE/SUB-MASSIVE PE (CONT'D)

Sub-massive PE
• The use of thrombolytics in patients w/ sub-massive PE (hemodynamically stable patients w/ echocardiographic
&/or biomarker evidence of RV dysfunction) is controversial
- Further studies are needed to show a clinically relevant improvement in the benefit-risk ratio of thrombolytic
treatment over traditional anticoagulant therapy in these patients
• Thrombolysis may be reasonably considered in select younger patients w/ sub-massive PE at low bleeding risk
or for those w/ high decompensation risk because of concomitant cardiopulmonary disease
Thrombolytic Agents
Alteplase (rt-PA)
• Has comparable thrombolytic capacity to Streptokinase & Urokinase but can be administered for a shorter
duration (2 hours)
• Preferred thrombolytic agent because of its shorter administration time
Streptokinase or Urokinase
• These 2 agents have similar thrombolytic effects in PE & have been shown to resolve PE comparatively at
24 hours & 3x that as seen w/ Heparin alone
• 12 hours of Urokinase have equivalent thrombolytic efficacy to 24 hours of Streptokinase
G INVASIVE PROCEDURES
• In patients w/ cardiac arrest or refractory circulatory collapse, extracorporeal membrane oxygenation (ECMO)
may be considered in combination w/ a catheter-directed treatment or surgical embolectomy
Catheter Extraction
• Catheter extraction involves the suction extraction of PE under fluoroscopy w/ ECG monitoring
• This approach should be reserved for highly compromised patients who cannot receive thrombolytic therapy
or whose status is so critical that it does not allow time to infuse thrombolytic therapy
Pulmonary Embolectomy
• Performed in emergency situations when more conservative measures have failed
• Should be reserved for the following patients:
- Massive PE (preferably angiographically documented)
- Hemodynamic instability despite Heparin & resuscitation
- High-risk PE or hemodynamically deteriorating patients w/ failure of thrombolytic therapy or contraindication
to its use
Thrombectomy
Percutaneous Venous Thrombectomy
• Patients w/ acute DVT should not be treated w/ percutaneous thrombectomy alone
Surgical Venous Thrombectomy
• Reduces acute symptoms & post-thrombotic morbidity in patients w/ acute iliofemoral DVT
• These patients have extensive venous thrombosis & have contraindications for anticoagulation & thrombolytic
therapy
Vena Caval Interruption
Inferior Vena Caval (IVC) Filters
• Should be considered in DVT/PE patients w/ contraindication or complication of anticoagulant therapy & in
patients w/ large, free-floating iliocaval thrombus or w/ a PE that developed during anticoagulation therapy
- May consider removing the IVC filter if anticoagulation has been established & is no longer contraindicated
• May also be considered in patients who suffer from recurrent VTE despite adequate anticoagulant therapy &
patients w/ chronic recurrent embolism w/ pulmonary hypertension
• May be indicated after surgical embolectomy or pulmonary thromboendarterectomy
• Preferable in patients w/ proximal DVT w/ active hemorrhage, platelet count <50,000 x 109/L, or previous
intracerebral hemorrhage
• Should not be used routinely in patients w/ DVT who are also being treated w/ anticoagulants
VTE - MANAGEMENT
B247
Dosage Guidelines

Drug Dosage Remarks
Apixaban Treatment of DVT or PE: Adverse Reactions
Initial dose: 10 mg PO • Hematologic effects (anemia, hemorrhage, contusion); GI
12 hrly x 7 days effect (nausea)
Max dose: 20 mg PO Special Instructions
Maintenance dose: 5 mg • Contraindicated in patients w/ clinically significant active
PO 12 hrly bleeding, hepatic disease w/ coagulopathy & clinically
Max dose: 10 mg PO relevant bleeding risk
Prevention of recurrent • Use w/ caution in hip fracture surgery, galactose intolerance,
DVT &/or PE: glucose-galactose malabsorption, severe renal impairment,
2.5 mg PO 12 hrly hepatic impairment
To be initiated following • Discontinue use in severe hemorrhage
completion of 6 mth • Monitor for signs of neurological impairment
treatment for DVT/PE or
w/ another anticoagulant
Edoxaban Treatment of DVT & PE Adverse Reactions
& prevention of • Hematologic effects (anemia, hemorrhage); GI effect
recurrent DVT & PE: (nausea); Other effects (abnormal LFT, increased blood
60 mg PO 24 hrly bilirubin & gammaglutamyltransferase, rash, pruritus)
following initial use of Special Instructions
parenteral anticoagulant • Edoxaban 15 mg is not indicated as monotherapy
for at least 5 days • Contraindicated in patients w/ clinically significant active
Patients w/ moderate or bleeding or conditions at risk for major bleeding, hepatic
severe renal impairment disease w/ coagulopathy & clinically relevant bleeding risk,
(CrCl 15-50 mL/min), ≤60 uncontrolled severe HTN, concomitant treatment w/ any other
kg body wt, or concomitant anticoagulants except when switching oral anticoagulant
use of P-gp inhibitors therapy or when UFH is given at doses necessary to maintain an
(Ciclosporin, Dronedarone, open central venous or arterial catheter
Erythromycin, • Use w/ caution in patients w/ an increased risk of bleeding,
Ketoconazole) are given moderate or severe renal impairment, mild or moderate hepatic
30 mg PO 24 hrly impairment, concomitant use of medicines affecting hemostasis
• Perform LFT prior to treatment & CrCl at the start of
therapy & thereafter
Fondaparinux Treatment of DVT & PE: Adverse Reactions
(Fondaparin) <50 kg body wt: 5 mg SC • Hematologic effects (hemorrhage, thrombocytopenia,
24 hrly anemia, purpura); Hepatic effect (abnormal LFT); Other
50-100 kg body wt: effect (edema)
7.5 mg SC 24 hrly • Less common effects: CNS effects (vertigo, dizziness,
>100 kg body wt: 10 mg headache); CV effect (hypotension); GI effects (N/V,
SC 24 hrly dyspepsia, constipation, diarrhea); Dermatologic effects
Continue x 5-9 days or (rash, pruritus); Rare allergic reactions
until oral coagulation is Special Instructions
established • Avoid in patients w/ clinically significant bleeding, severe
renal impairment or in those w/ confirmed HIT
• Use w/ caution in patients w/ an increased risk of hemorrhage;
acute GI ulcer, recent intracranial hemorrhage, or shortly after
brain, spinal or ophthalmic surgery; use w/ caution in patients
<50 kg, patients w/ moderate renal impairment, severe hepatic
impairment, w/ history of HIT, elderly >75 yr
employed in patients anticoagulated or to be anticoagulated
VTE - MANAGEMENT
for thromboprophylaxis
• Monitoring of platelets is recommended at baseline & at the
end of treatment

B248
Dosage Guidelines

Drug Dosage Remarks
Rivaroxaban Treatment of Adverse Reactions
DVT & PE: • Hematologic effects (hemorrhage, anemia, decreased hemoglobin);
Days 1-21: 15 mg Hepatic effect (increased ALT & AST); CNS effects (dizziness,
PO 12 hrly headache, syncope); CV effects (tachycardia, hypotension); GI effect
Max dose: (nausea); Dermatologic effects (pruritus, rashes); Other effects (fever,
30 mg/day peripheral edema, postprocedural hemorrhage)
Days 22 Special Instructions
onwards: 20 mg • Contraindicated in patients w/ clinically significant active bleeding,
PO 24 hrly pregnant, lactating & hepatic disease associated w/ coagulopathy that
Max dose: can lead to relevant risk of bleeding
20 mg/day • Use w/ caution in patients w/ hemorrhagic risk, lactose or galactose
intolerance, & those w/ moderate to severe renal impairment
Dabigatran Treatment of Adverse Reactions
etexilate acute DVT &/or • Hematologic effects (hemorrhage, anemia, hematoma,
PE: 150 mg PO thrombocytopenia); Renal effect (hematuria); GI effects (dyspepsia,
12 hrly (after N/V, GI hemorrhage, abdominal pain, diarrhea, gastroesophagitis,
5-10 days of abnormal hepatic function); Other effects (wound secretion,
parenteral postprocedural discharge)
anticoagulation) Special Instructions
Prevention of • Contraindicated in patients w/ severe renal impairment, hemorrhagic
recurrent DVT manifestations, bleeding diathesis, patients w/ spontaneous or
&/or PE: pharmacological hemostatic impairment, organ lesions at risk of
150 mg PO clinically significant bleeding (including hemorrhagic stroke within
12 hrly the last 6 mth, patients on concomitant therapy w/ systemic
Ketoconazole, prosthetic heart valve replacement
• Use w/ caution in hepatic impairment, renal insufficiency, increased
hemorrhagic risk, spinal/epidural anesthesia, lumbar puncture
• Discontinue use in patients who develop acute renal failure
Enzymes
Alteplase Loading dose: Adverse Reactions
(rt-PA) 10 mg as an IV • Hematologic effects (hemorrhage especially from puncture sites,
bolus over severe internal bleeding, intracranial hemorrhage has occurred); GI
1-2 min effects (N/V, abdominal pain)
Followed by: • Rarely: Allergic reactions (rashes, flushing, urticaria & rarely
90 mg IV anaphylactic & serum sickness-like symptoms)
infusion over 2 hr • Infusion may be associated w/ hypotension (both direct & as a result of
Max total dose: reperfusion), bradycardia & arrhythmias may occur because of reperfusion
100 mg (1.5 mg/ • Break-up of clots may occasionally cause emboli elsewhere hence the
kg in patients need for Heparin prophylaxis
<65 kg) Special Instructions
• See page 7 of this disease management chart for specific contraindications
Reteplase Treatment of PE: Adverse Reactions
(r-PA) 10 units via slow • Hematologic effects (hemorrhage, intracranial bleeding); CV effects
IV over 1-2 min (hypotension, hypertension, pericarditis, bradycardia, thrombosis)
after the onset of Special Instructions
symptoms • See page 7 of this disease management chart for specific contraindications
May repeat dose • Use w/ caution in patients w/ recent major surgery, CVD, recent GI/
once, 30 min after
VTE - MANAGEMENT
GU bleed, hypertension, severe hepatic/renal impairment,

the start of 1st inj arrhythmias, cholesterol embolism

B249
Dosage Guidelines

Drug Dosage Remarks
Enzymes (Cont’d)
Streptokinase Loading dose: Adverse Reactions
250,000 IU IV over 30 min • Hematologic effects (hemorrhage especially from
Followed by: puncture sites, severe internal bleeding, intracranial
1.5 MIU/hr IV infusion x 6 hr or hemorrhage has occurred); Allergic reactions
100,000 IU/hr IV infusion x 72 hr (rashes, flushing, urticaria & rarely anaphylactic &
for DVT or x 24 hr for PE serum sickness-like symptoms); Other effects (fever,
chills w/ back & abdominal pain); GI effects (N/V);
Begin Heparin 3-4 hr after Guillain-Barré syndrome has occurred
Streptokinase infusion or when
aPTT is <100 sec • Infusion may be associated w/ hypotension (both
direct & as a result of reperfusion), bradycardia &
Urokinase Treatment of massive acute PE: arrhythmias may occur because of reperfusion
Loading dose: • Break-up of clots may occasionally cause emboli
4400 IU/kg IV in 15 mL soln over elsewhere
10 min • Serious allergic reactions may be less likely to occur
Followed by: w/ Urokinase than w/ Streptokinase
4400 IU/kg/hr IV infusion x 12 hr Special Instructions
Anticoagulation should be started • See page 7 of this disease management chart for
once aPTT has decreased to <2x specific contraindications
the normal control value. If • Anti-streptokinase antibodies are formed after
Heparin is used, do not give a about 5 days after Streptokinase use
loading dose of Heparin - These antibodies may cause resistance or
hypersensitivity to subsequent doses of
Streptokinase
- Recommend not to administer Streptokinase
5 days-12 mth after 1st administration (alternative
thrombolytic not including Anistreplase may be
used)
Heparin Group
Bemiparin Treatment of DVT: 115 IU Adverse Reactions
sodium anti-Xa/kg/day SC during 7±2 • Hematologic effects (hemorrhage,
days which corresponds to: thrombocytopenia); Inj site reaction; Rare
<50 kg: 5,000 IU anti-Xa hypersensitivity reactions (anaphylaxis); Effects that
50-70 kg: 7,500 IU anti-Xa may occur w/ long-term use (osteoporosis,
70-100 kg: 10,000 IU anti-Xa alopecia)
100-120 kg: 12,500 IU anti-Xa Special Instructions
>120 kg: 115 IU anti-Xa/kg/day • Avoid in patients w/ active major bleeding, patients
w/ positive in vitro test for antiplatelet antibody to
Patients w/ DVT & transitory the specific heparin, injury or surgery to CNS, eyes
risk factors: 3,500 IU/day SC up or ears
to a max of 3 mth
• Use w/ caution in patients w/ hemorrhagic
Dalteparin 200 IU/kg SC 24 hrly or disorders (including history of Heparin-induced
sodium 100 IU/kg SC 12 hrly for patients thrombocytopenia), peptic ulcer, cerebrovascular
w/ increased risk of bleeding disorders, uncontrolled hypertension, hepatic or
Max dose: 18,000 IU/day renal impairment, surgery at sites at risk for
hemorrhage, hypersensitivity to Heparin
Enoxaparin 1.5 mg/kg (150 anti-Xa IU/kg) SC
• Consider risk vs benefit before neuraxial
24 hrly or
intervention is employed in patients anticoagulated
1 mg/kg (100 anti-Xa IU/kg) SC
or to be anticoagulated for thromboprophylaxis
VTE - MANAGEMENT
12 hrly
• Monitoring of platelets is recommended at baseline
& periodically during treatment

B250
Dosage Guidelines

Drug Dosage Remarks
Heparin Group (Cont’d)
Heparin Wt-adjusted dosing based on Adverse Reactions
(Unfractionated nomogram • Hematologic effects (hemorrhage,
Heparin) or thrombocytopenia); Inj site reaction;
UFH IV infusion: Rare hypersensitivity reactions
Loading dose: 5000 U IV (anaphylaxis); Effects that may occur w/
Loading dose for severe PE: 10,000 U IV long-term use (osteoporosis, alopecia)
Followed by: 18 U/kg or 1000-2000 U/hr • Sulodexide
continuous IV infusion
(adjust dose based on aPTT) - Cap: N/V, diarrhea, epigastralgias
5000-10,000 U intermittent IV inj 4-6 hrly • Avoid in patients w/ active major
(adjust dose based on aPTT) bleeding, patients w/ positive in vitro
or test for antiplatelet antibody to the
SC UFH: 15,000 U SC 12 hrly or 10,000 U specific heparin, injury or surgery to
SC 8 hrly (adjust dose based on aPTT) CNS, eyes or ears
Nadroparin 86 anti-Xa IU/kg SC 12 hrly x 10 days • Use w/ caution in patients w/
calcium or hemorrhagic disorders (including
history of Heparin-induced
171 anti-Xa IU/kg SC 24 hrly x 10 days thrombocytopenia), peptic ulcer,
Parnaparin 6400 anti-Xa IU SC 24 hrly x 7-10 days cerebrovascular disorders, uncontrolled
sodium hypertension, hepatic or renal
impairment, surgery at sites at risk for
Reviparin sodium 35-45 kg: 3500 anti-Xa IU SC 12 hrly hemorrhage, hypersensitivity to Heparin
46-60 kg: 4200 anti-Xa IU SC 12 hrly • Consider risk vs benefit before neuraxial
>60 kg: 6300 anti-Xa IU SC 12 hrly intervention is employed in patients
Doses to be given w/ an oral anticoagulant anticoagulated or to be anticoagulated
x 5-7 days for thromboprophylaxis
Sulodexide 250-500 mg PO 12 hrly or • Monitoring of platelets is recommended at
600 LSU IM/IV 24 hrly baseline & periodically during treatment
Tinzaparin sodium 175 anti-Xa IU/kg SC 24 hrly
UNFRACTIONATED HEPARIN (UFH) INFUSION RATE ADJUSTED ACCORDING TO BODY WT & APTT
• Loading dose: 80 U/kg IV, followed by IV infusion of 18 U/kg/hr
• Monitor aPTT 6 hrly for the 1st 24 hr to keep aPTT within therapeutic range (1.5-2.3 x control) & adjust
subsequent dosage according to aPTT
- Thereafter monitor aPTT once daily unless it is outside therapeutic range
• Dose adjusted based on aPTT:
• aPTT <35 sec (<1.2 x mean normal) Give 80 U/kg IV bolus, then increase infusion rate
by 4 U/kg/hr
• aPTT 35-45 sec (1.2-1.5 x mean normal) Give 40 U/kg IV bolus, then increase infusion rate
by 2 U/kg/hr
• aPTT 46-70 sec (1.5-2.3 x mean normal) No change
• aPTT 71-90 sec (2.3-3 x mean normal) Decrease infusion rate by 2 U/kg/hr
• aPTT >90 sec (>3 x mean normal) Stop infusion for 1 hr then decrease infusion rate
VTE - MANAGEMENT
by 3 U/kg/hr

B251
Dosage Guidelines

Drug Dosage Remarks
Platelet Aggregation Inhibitor excluding Heparin
Aspirin1 Prophylaxis against Adverse Reactions
(Acetylsalicylic DVT: 100 mg PO • Hematologic effects (thrombocytopenia, anemia); GI effects
acid) 24 hrly (gastric hemorrhage, N/V, dyspepsia); Other effects
(salicylate sensitivity, tinnitus, severe hypoglycemia, Reye’s
syndrome)
• Contraindicated in patients w/ salicylate-induced asthma,
active peptic ulcer, hemorrhagic diathesis, severe cardiac or
renal failure
• Combination w/ >15 mg/wk Methotrexate is
contraindicated
• Use w/ caution in patients w/ renal impairment, G6PD
insufficiency, flu, chickenpox, hemorrhagic fever, GI
ulceration, asthma
Warfarin Initial dose: 5-10 mg Adverse Reactions
PO/IV 24 hrly x 2 days • Hemorrhage can occur even within therapeutic INR levels
Followed by • Less common effects: Cholesterol embolization (skin
subsequent dose that necrosis & purple discoloration of the toes); GI effects (N/V,
should be adjusted to diarrhea); Other effects (alopecia, skin reactions, hepatic
target INR = 2.5 (INR dysfunction, pancreatitis, jaundice, fever)
range 2.0-3.0) Special Instructions
Maintenance dose: • Patients should be counseled on the risks of therapy along
2-10 mg/day w/ drug & food interactions
• Avoid in patients w/ active or at risk of hemorrhage, PUD,
severe wounds, cerebrovascular disorders & bacterial
endocarditis
• Use w/ extreme caution or not at all in patients w/ severe
renal or hepatic impairment
• INR monitoring is usually performed daily until the
therapeutic range (2.0-3.0) has been achieved
- Then INR is monitored 2-3x/wk for 2 wk
- Then INR is monitored wkly or less often depending on
the stability of INR
VTE - MANAGEMENT

B252
Venous Thromboembolism -
Prevention (1 of 17)
1
ASSESSMENT UPON ADMISSION
Patient is admitted to hospital for major
trauma, surgery or acute medical illness
2 No
Yes Patient is at
Patient is at EVALUATION moderate to
low risk for high risk
Is patient at low risk
VTE for VTE
for VTE?
THROMBOPROPHYLAXIS THROMBOPROPHYLAXIS
A Non-pharmacological therapy A Non-pharmacological therapy
• General measures • General measures
Early & aggressive ambulation Early & aggressive ambulation
is recommended is recommended
• Mechanical measures • Mechanical measures
- Graduated compression - GCS
stockings (GCS) - IPC device
- Intermittent pneumatic - VFP
compression (IPC) device - IVC filter
- Venous foot pumps (VFP) B Pharmacological therapy
- Inferior vena cava (IVC) filter • Low-dose unfractionated
Heparin (LDUH)
• Low-molecular-weight Heparin
(LMWH)
• Factor Xa inhibitor
• Direct thrombin inhibitor
• Aspirin
• Warfarin
SPECIFIC GROUP
RECOMMENDATIONS
See page 9
B253
Venous Thromboembolism - Prevention (2 of 17)
VENOUS THROMBOEMBOLISM (VTE)

VTE - PREVENTION
• Most commonly manifested as pulmonary embolism (PE) & deep venous thrombosis (DVT), & is associated
w/ significant morbidity & mortality
- ⅓ of patients present w/ symptoms of PE & ⅔ w/ DVT
- Also manifests as superficial vein thrombosis (SVT), a less severe form of DVT
• One of the most common life-threatening cardiovascular diseases in the United States & w/ increasing incidence
& mortality rates in Asia
Pathogenesis
• Virchow’s triad theorizes 3 factors contributing to the development of VTE: Hypercoagulability, endothelial
damage, & stasis
• Hypercoagulability has been associated w/ factor V Leiden mutation & prothrombin gene mutation
- Cancer also produces a hypercoagulable state due to the procoagulant activity produced by malignant cells
& also secondary to effects of chemotherapeutic agents
• Major contributing risk factors include history of trauma, surgical procedures, spinal cord injury, long bone
fractures, & previous VTE
1 ASSESSMENT
• All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of VTE &
bleeding before starting prophylaxis of VTE
- Balance the risk of VTE against bleeding as the medicines used for VTE prevention are associated w/ an
increased bleeding risk
- Studies show that appropriate VTE prophylaxis should be given to surgical patients in Asia who are at risk
for VTE
• Assess critically ill patients more frequently for VTE & bleeding risk
Assessment of Individual Risk Should Include:
Personal Risk Factors for VTE
• Increasing age
- There is exponential increase in risk w/ increasing age (>60 years old)
• Marked obesity - BMI ≥30 kg/m2
• Varicose veins, venous compression caused by tumor, arterial abnormality or hematoma
• Previous PE or DVT, or 1st-degree relative w/ VTE history
• Pregnancy or puerperium (within 6 weeks)
- Preexisting acquired thrombophilia (antiphospholipid syndrome)
• Hormone therapy
- Oral combined contraceptives, estrogen-containing contraceptives, hormone replacement therapy (HRT),
Raloxifene, Tamoxifen (increased risk by 3x)
- High-dose progestins (increased risk by 6x)
• Thrombophilias (inherited or acquired)
- Phospholipid antibody syndrome, deficiencies in antithrombin III, protein S, protein C, factor V Leiden
mutation, prothrombin gene mutation
• Malignancy (active or occult)
- Especially pelvic, abdominal, esophageal, lung or metastatic cancer
• Myeloproliferative disorders
- Polycythemia, paraproteinemia
• Immobility (bed rest >3-4 days), lower extremity paresis
• Smoking
B254
VTE - PREVENTION
Assessment of Individual Risk Should Include: (Cont’d)
Risk Factors Related to Trauma, Surgical Procedure, Severe Infection or Acute Medical Illness
• Trauma
- Especially spinal cord injury, multiple trauma or pelvis, hip or lower limb fractures
• Surgery
- Risk will depend on site, technique, duration of the procedure, type of anesthetic, presence of infection &
duration of post-op immobilization
- Hip & knee replacement surgery have a higher risk of VTE
- Duration of surgery & anesthesia >90 minutes or 60 minutes if it involves the pelvis or lower limb
- General anesthesia has higher risk of VTE than spinal/epidural
• Cancer therapy
- Chemotherapy, angiogenesis inhibitors, radiotherapy
• Behcet’s disease/paroxysmal nocturnal hemoglobinuria
• Erythropoiesis-stimulating agents
• Cardiac dysfunction
- Uncompensated congestive heart failure (CHF), recent myocardial infarction (MI)/acute stroke
• Nephrotic syndrome
• Inflammatory bowel disease (IBD)
• Systemic lupus erythematosus, systemic sclerosis
• Central venous catheterization
• Acute respiratory failure
• Chronic renal disease
• Coronavirus disease 2019 (COVID-19)
• Critical care admission
Risk Factors for Bleeding
• Personal or family history of bleeding disorders
• Active or recent (within the week) bleeding
• Acute hemorrhagic stroke
• Ulcerative gastrointestinal disease, eg active peptic ulcer
• Platelet count <50,000/microL
• Medications used, eg NSAIDs, antiplatelets, anticoagulants, thrombolytics
• Liver disease or abnormal renal function
• Uncontrolled hypertension
• Procedures w/ critical bleeding consequences, eg epidural or spinal anesthesia, lumbar puncture, intracranial
or neurosurgery, head & neck surgery or orthopedic surgery
2 EVALUATION
VTE Risk Assessment Tools
Padua Risk Assessment Prediction Score
• Used to assess hospitalized medical patients’ risk for VTE
• Scores ≥4 indicated high VTE risk
Points Medical History
3 Cancer, past VTE, immobile, thrombophilic
2 History of trauma or surgery ≤1 month prior to assessment
1 Age ≥70 years old, CHF, respiratory failure, acute MI, ischemic cerebrovascular accident,
BMI ≥30 kg/m2, hormonal therapy, infections, rheumatologic diseases
Reference: Institute for Clinical Systems Improvement. Venous thromboembolism prophylaxis guideline. 2012.
• Pharmacoprophylaxis is suggested in patients at high risk for VTE but at low risk for bleeding
• Patients at high risk for both VTE & bleeding should also be given intermittent pneumatic compression
• No prophylactic measures are needed for patients at low risk for VTE &/or bleeding
B255
VTE - PREVENTION
VTE Risk Assessment Tools (Cont’d)

Caprini VTE Risk Assessment
• Used to assess the risk for VTE of patients scheduled for surgery, surgical patients in the intensive care unit
(ICU) & patients on gynecologic oncology treatment
• Also identifies surgical patients who may or may not benefit from pharmacological prophylaxis
• Points are given depending on different risk factors
Risk factors equivalent to 1 point each: Risk factors equivalent to 1 point each for female
• Age 41-60 years old patients:
• Planned minor surgical procedure • Oral contraceptive or HRT
• Major surgery <1 month prior • Pregnant or <1 month postpartum
• Varicose veins • (+) unexplained stillborn birth, recurrent (>3)
• History of IBD spontaneous abortion, premature birth w/
• Edematous lower extremities toxemia, growth-restricted infant
• Obesity (BMI >25 kg/m2) Risk factors equivalent to 3 points each:
• Acute MI • Age ≥75 years old
• CHF <1 month prior • History of DVT/PE
• Sepsis <1 month prior • Family history of thrombosis
• Serious pulmonary disease including pneumonia • Positive factor V Leiden
< 1 month prior • Positive prothrombin A
• Abnormal lung function (COPD) • Increased serum homocysteine
• Medical patient advised bed rest • Positive lupus anticoagulant
• Other risk factors • Increased anticardiolipin antibodies
Risk factors equivalent to 2 points each: • Heparin-induced thrombocytopenia
• Age 61-74 years old • Congenital or acquired thrombophilia
• Arthroscopic surgery Risk factors equivalent to 5 points each:
• Present or history of malignancy • Elective major lower extremity arthroplasty
• Major surgery of >45 minutes duration • Hip/pelvis/lower extremity fracture of
• Laparoscopic surgery of >45 minutes duration <1 month
• Patient confined to bed for >72 hours • Cerebrovascular accident/stroke <1 month
• Plaster cast applied, immobilized for <1 month • Multiple trauma <1 month
• Central venous access • Acute spinal cord injury/paralysis <1 month
Reference: Institute for Clinical Systems Improvement. Venous thromboembolism prophylaxis guideline. 2012.
VTE Risk Category Caprini Score

Very Low 0
Low 1-2
Moderate 3-4
High ≥5
• For prophylactic measures against bleeding according to VTE risk, please see page 9
Other Medical Conditions
• Acute MI (please see Myocardial Infarction w/ ST-Segment Elevation disease management chart for further
information)
• Acute stroke (please see Ischemic Stroke & Intracerebral Hemorrhage disease management charts for further
information)
• Routine thromboprophylaxis is recommended in the following:
- Burn patients who have ≥1 additional VTE risk factors
- ICU & septic patients
- Patients w/ severe respiratory disease
A THROMBOPROPHYLAXIS - NON-PHARMACOLOGICAL THERAPY

General Measures for Prophylaxis of VTE
Mobilization
• Early mobilization & leg exercises for any patient recently immobilized are recommended
• Immobility increases risk of DVT by approximately 10x
• Early & frequent ambulation may be recommended in patients undergoing the following procedures:
- Vascular surgery without additional thromboembolic risk factors
- Transurethral or other low-risk urological procedures
- Laparoscopic procedure
B256
A THROMBOPROPHYLAXIS - NON-PHARMACOLOGICAL THERAPY (CONT’D)
VTE - PREVENTION
General Measures for Prophylaxis of VTE (Cont’d)
Hydration
• Immobilized patients should be adequately hydrated
• Hemoconcentration can reduce blood flow especially in the deep veins of immobile patients
Pre-Operative/Operative Measures
• Patient should be advised to defer antiplatelet agent intake prior to elective hip/knee arthroplasty
• Neuraxial anesthesia is preferred for patients at risk for VTE undergoing elective hip/knee arthroplasty
Mechanical Measures
• Increase mean blood flow velocity in the leg veins & reduce venous stasis
• Less efficacious than pharmacologic thromboprophylaxis in decreasing the risk of DVT
- Not as intensively studied as pharmacologic prophylaxis
- No established standards for size, pressure or physiologic standards
• Acceptable alternative in patients in whom risk of bleeding outweighs the benefits of pharmacotherapeutic
DVT prophylaxis, though it may be used in combination w/ anticoagulant prophylaxis to improve efficacy
- The Asian Venous Thrombosis Forum recommends mechanical prophylaxis in those whose risk of bleeding
is high & combined mechanical & pharmacological prophylaxis in those whose risk of VTE is increased
• The 2018 American Society of Hematology guidelines suggest the use of the following interventions in acutely
or critically ill medical patients:
- Mechanical prophylaxis over no VTE prophylaxis
- Mechanical prophylaxis alone over combined pharmacological & mechanical VTE prophylaxis due to the
undesirable consequences likely outweighing the desirable effects
- GCS or pneumatic compression devices in those receiving mechanical VTE prophylaxis
• The 2019 American Society of Hematology guidelines suggest the use of mechanical prophylaxis over no VTE
prophylaxis in patients undergoing major surgery
- Intermittent compression devices are preferred over GCS
• Evaluate patient’s suitability based on the risk factors
• Emphasis must be made toward proper use of & optimal compliance w/ the mechanical device
• Contraindications: Patients at risk of ischemic skin necrosis
Graduated Compression Stockings (GCS)
• Compress the lower leg veins in a graded fashion reducing venous distension & increasing venous return to
the deep venous system
• May be used for DVT prophylaxis in surgical patients w/ no contraindication for use of GCS
- Although little evidence supports the efficacy of GCS in preventing VTE
• May be used in chronic DVT patients to improve leg pain & swelling more rapidly
- To prevent postthrombotic syndrome, routine use of GCS in patients w/ acute DVT is not recommended
• Correct size & alignment is needed
- It is important to measure the patient correctly & to use the correct size
- Pressure of 16-20 mmHg at the ankle in the supine position w/ graduated compression to the knee or above
- Assure that toe hole is aligned under toe
- Check fitting daily for change in leg circumference
- Do not fold down
- Remove daily for ≤30 minutes
• Contraindications: Massive leg edema, pulmonary edema, severe peripheral arterial disease, anatomic leg
deformity, dermatitis, recent skin graft (within 6 months), loss of skin integrity
• Complications: Compartment syndrome, skin ulceration & common peroneal nerve palsy
Intermittent Pneumatic Compression (IPC) Devices
• Periodically compress calf &/or thighs & stimulate fibrinolysis
• Have been shown to be more effective than GCS in high-risk patients in combination w/ anticoagulants or
when anticoagulants are contraindicated
• When combined w/ LDUH, it reduces the risk of symptomatic PE in cardiac surgery patients
• Have been shown to be effective in prophylaxis of asymptomatic DVT in surgical patients
• May be used in acute stroke patients for 30 days or until discharged or mobile
• Many times IPC devices are applied immediately prior to surgery & are replaced by GCS after surgery because
IPC devices may cause discomfort in the conscious patient
• Complications: Compartment syndrome, skin ulceration & common peroneal nerve palsy
Venous Foot Pumps (VFP)
• Deliver external compression to the venous system of the foot increasing venous return thus reducing venous
stasis in the lower extremity
• For orthopedic surgery patients who are unable to bear own weight
B257
A THROMBOPROPHYLAXIS - NON-PHARMACOLOGICAL THERAPY (CONT’D)

VTE - PREVENTION
Mechanical Measures (Cont’d)

Inferior Vena Cava (IVC) Filters
• May be considered in patients w/ severe PE who have received anticoagulant therapy & those w/ contraindications
to anticoagulants
• Benefits should be weighed against potential complications when to be used in patients w/ progressive or
recurrent VTE despite anticoagulant therapy
• The American College of Chest Physicians does not recommend the use of IVC filters in patients w/ acute
DVT or PE who are treated w/ anticoagulants
• The 2019 American Society of Hematology suggests against using IVC filters for VTE prophylaxis in patients
undergoing major surgery
Electrical Stimulation
• Device that stimulates the intrinsic foot muscles to contract & consequently compress the plantar venous
plexus
• Designed to increase the venous blood flow velocity out of the leg to reduce the incidence of VTE after surgery
• May be effective in reducing venous stasis & edema
Prophylaxis Decisions
• Carefully weigh the benefits of prophylaxis against the risk of bleeding when deciding on VTE prevention
- Recent Asian studies showed reduction in risk of VTE w/ postoperative thromboprophylaxis w/ no significant
increased risk in bleeding
• Decision on which type of prophylaxis to be given must be decided individually for each patient
- For patients undergoing major surgery, mechanical prophylaxis may be used for patients w/ high bleeding
risk
- Pharmacological or mechanical prophylaxis may be used over no prophylaxis for patients w/ moderate or
high VTE risk
• Consider prophylaxis in patients whose long-term anticoagulation has been interrupted
• Routine VTE prophylaxis is not recommended for low-risk patients (those w/ illness, immobility, infection or
minor injury), chronically ill medical patients or nursing home patients unless risk status changes
• The 2018 American Society of Hematology guidelines suggest the use of the following interventions in acutely
or critically ill medical patients:
- Pharmacological over mechanical VTE prophylaxis
- Pharmacological prophylaxis alone over combined pharmacological & mechanical VTE prophylaxis due to
the undesirable consequences likely outweighing the desirable effects
- Inpatient-only VTE prophylaxis is recommended over extended-duration outpatient prophylaxis
Considerations
• Clinical judgment
• Review of literature for group recommendations
• Patient’s unique risks for thrombosis
• Patient’s renal function
• Potential for adverse effects
• Local availability of products
Contraindications to Anticoagulant Prophylaxis
• Active bleeding, history of or high risk of bleeding (eg hemophilia, thrombocytopenia, GI bleeding)
• Severe hepatic disease
• Currently on anticoagulation treatment
• Other factors eg high risk of falls, on palliative treatment
B THROMBOPROPHYLAXIS - PHARMACOLOGICAL THERAPY

ANTICOAGULANTS
• Acutely ill medical patients or stroke patients may be given unfractionated Heparin, LMWH or Fondaparinux
for VTE prophylaxis (LMWH or Fondaparinux preferred over unfractionated Heparin) rather than no parenteral
• Critically ill medical patients may be given unfractionated Heparin or LMWH for VTE prophylaxis (LMWH
preferred over unfractionated Heparin) rather than no Heparin therapy
B258
B THROMBOPROPHYLAXIS - PHARMACOLOGICAL THERAPY (CONT’D)
VTE - PREVENTION
ANTICOAGULANTS (Cont’d)
Low-Dose Unfractionated Heparin (LDUH)
• Inhibits clotting of blood through enhancement of antithrombin III activity; antithrombin III inactivates
thrombin (factor IIa), factor Xa, factor IXa, factor XIIa & factor XIa
- Unfractionated heparin (UFH) also inhibits the activation of factors V & VIII by thrombin
• In surgical patients & high-risk medical patients, SC LDUH has been shown to significantly reduce the incidence
of asymptomatic DVT, symptomatic DVT & PE, fatal PE & total mortality
- The use of LDUH has been shown to result in an increase in major bleeding but there is no increase in fatal bleeding
• Monitoring of the anticoagulant effect is not required when SC LDUH is used
• To detect Heparin-induced thrombocytopenia (HIT), which occurs in 2-3% of patients receiving LDUH,
baseline platelet count should be obtained & regularly monitored
Low-Molecular-Weight Heparin (LMWH)
• Eg Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Tinzaparin, Danaparoid
• Similar to Heparin, these compounds enhance the action of antithrombin III but they have a higher ratio of
anti-factor Xa to anti-IIa activity than Heparin
- Produce a more predictable anticoagulant response than Heparin
- They have less effect on platelet activity
• It has been shown that SC LMWH is as effective as LDUH in surgical & medical patients in decreasing the
incidence of asymptomatic DVT, symptomatic DVT & PE, fatal PE & total mortality
- Risk of bleeding is similar to LDUH
• Preferred over direct oral anticoagulants (including factor Xa inhibitors & direct thrombin inhibitors) as an
inpatient-only VTE prophylaxis in the acutely ill hospitalized medical patient
• Danaparoid may be used in patients who developed severe thrombocytopenia from LMWH or Heparin
• Monitoring of the anticoagulant effect is not required
• HIT is less common w/ LMWH, occurring in <1% of patients, but baseline platelet count should still be obtained
& monitored
• Eg Apixaban, Betrixaban, Edoxaban, Fondaparinux, Rivaroxaban
Apixaban
• A direct & competitive factor Xa inhibitor that does not require antithrombin III for antithrombotic activity
• Indicated for the prevention of VTE in patients undergoing hip or knee placement surgery
Betrixaban
• Indicated for the prevention of VTE in hospitalized patients at increased risk for DVT & PE due to immobilization
or other risk factors
• Specifically blocks factor Xa, thereby decreasing thrombin generation; also inhibits free factor Xa & prothrombinase
activity
• Studies showed lesser adverse events (symptomatic DVT, non-fatal PE) in patients given Betrixaban compared
to patients on Enoxaparin therapy
Edoxaban
• Prophylactic option against stroke & systemic embolism in patients w/ non-valvular atrial fibrillation
• Requires initial therapy w/ parenteral anticoagulants prior to starting therapy
• Should only be used in patients w/ high creatinine clearance (>95 mL/min)
• Some studies have indicated the efficacy of Edoxaban as prophylaxis against VTE after total knee or hip
replacement & hip fracture surgery
- Several studies have shown that the efficacy of Edoxaban for VTE prevention after surgery was comparable
to Enoxaparin & Warfarin
Fondaparinux
• Used for prophylaxis of VTE in patients undergoing hip fracture, hip replacement or knee replacement surgery
or abdominal surgery
• Specifically inhibits factor Xa, which results in effective inhibition of thrombin generation
• Studies have shown that in patients undergoing major orthopedic surgery, factor Xa inhibitor was more effective
than LMWH in preventing VTE
- Risk of clinically relevant bleeding is similar to LMWH
• Monitoring of the anticoagulant effect is not required
• Moderate thrombocytopenia has occurred & platelet count should be monitored
B259
B THROMBOPROPHYLAXIS - PHARMACOLOGICAL THERAPY (CONT’D)

VTE - PREVENTION
ANTICOAGULANTS (Cont’d)
Rivaroxaban
• Recommended prophylactic agent for VTE following elective total hip or knee replacement
• Also used for the prevention of systemic embolism in patients w/ non-valvular atrial fibrillation
• Increased risk of stroke was noted upon discontinuation of Rivaroxaban in clinical trials of patients w/ atrial
fibrillation
- Consider adding alternative anticoagulant when Rivaroxaban is discontinued for reasons other than bleeding
• Spinal or epidural hematomas, including subsequent paralysis, may occur w/ neuraxial anesthesia (epidural
or spinal anesthesia) or spinal puncture in patients who are anticoagulated
Direct Thrombin Inhibitors
• Eg Argatroban, Bivalirudin, Dabigatran, Hirudin
Argatroban
• Competitive inhibitor of thrombin & forms a reversible complex w/ thrombin
• For prevention & treatment of HIT-associated thrombosis & for anticoagulation during percutaneous coronary
interventions when Heparin is contraindicated due to history of HIT
Bivalirudin
• An analog of Hirudin
• Anticoagulant used w/ Aspirin in patients undergoing percutaneous coronary interventions including those
w/ or at risk of HIT
Dabigatran
• Used for prophylaxis of VTE in patients who will undergo elective orthopedic surgery, eg total hip or knee
replacement
• Also has use in preventing stroke & systemic embolization in patients w/ non-valvular atrial fibrillation
• Investigation of postmarketing reports of serious bleeding rates is ongoing
• Patients w/ atrial fibrillation are advised against discontinuing Dabigatran without talking to their physicians
because bleeding risks do not outweigh the stroke prevention benefits of Dabigatran
Hirudin
• Inhibits & forms an irreversible complex w/ thrombin
• 2 recombinant forms
- Desirudin - used for post-op thromboprophylaxis in patients undergoing hip arthroplasty in Europe
- Lepirudin - used for treatment of thrombosis complicating HIT in North America
• Effective in preventing asymptomatic DVT but use is limited by necessary INR monitoring, bleeding risk &
delay in onset of action
Antiplatelet
Aspirin
• May be considered for the prevention of recurrent VTE in patients w/ unprovoked proximal DVT or PE who
discontinued anticoagulant therapy
• May be used w/ mechanical compression for VTE prophylaxis after hip or knee replacement surgery in the
absence of major risk factors for VTE or bleeding
• Consider using Aspirin rather than no VTE prophylaxis in long-distance travelers (>4 hours) who are at
increased VTE risk & in whom LMWH or GCS is not suitable
• Prophylactic efficacy is inferior to LMWH & anticoagulants
• Not to be used as an alternative therapy if patient has no contraindications & is willing to undergo treatment
w/ anticoagulants
Warfarin
• May be appropriate when used for long-term prophylaxis in patients who are immobilized by illness, trauma
or surgery
• Inhibits the synthesis of the vitamin K-dependent coagulant proteins (factors II, VII, IX, & X) & inhibits at
least 2 vitamin K-dependent anticoagulant factors (proteins C & S)
• Effective in preventing asymptomatic DVT but use is limited by necessary INR monitoring, bleeding risk &
delay in onset of action
Antithrombin III
• A human plasma-derived protein which acts to inhibit thrombin & other activated clotting factors (eg factors
IX, X, XI, XII)
• Cofactor through which heparin exerts its effects
• Genetic & acquired insufficiency of antithrombin III is associated w/ susceptibility to thromboembolic disorders
• Goal of therapy is to restore plasma-antithrombin III to normal level
• Dose & duration of treatment should be individualized based on patient’s pretreatment condition & presence
of active coagulation
B260
PATIENT AT MODERATE TO HIGH RISK FOR VTE
VTE - PREVENTION
SPECIFIC GROUP DEPENDING ON RECOMMENDED PREVENTION
RISK FACTOR FOR VTE
Moderate-risk general surgery Any of the following would be appropriate:
• Major surgery for benign disease • LDUH
• LMWH
• Fondaparinux
High-risk general surgery Any of the following would be appropriate:
• Major procedure for cancer • LDUH 8 hourly
• LMWH
• Fondaparinux
High-risk general surgery patients w/ Any of the following would be appropriate:
multiple risk factors • LDUH 8 hourly
• LMWH
• Fondaparinux
Combined w/:
• GCS &/or IPC
Patients w/ high risk of bleeding • GCS &/or IPC until bleeding decreases then substitute or
• General surgery add pharmacological thromboprophylaxis
• Urologic surgery
• Critical care patients
Major vascular surgery patients w/ Any of the following would be appropriate:
additional thromboembolic risk factors • LDUH
• LMWH
• Fondaparinux
Mechanical prophylaxis may also be added
Major gynecologic surgery for benign Any of the following would be appropriate:
disease without additional risk factors • LDUH 12 hourly
• LMWH
• IPC started prior to surgery & continued until patient is
ambulatory
Extensive gynecologic surgery for Any of the following would be appropriate:
malignancy & for patients w/ additional • LDUH 8 hourly
risk factors • LMWH
• IPC started prior to surgery & continued until patient is
ambulatory
Any of the following alternatives:
• LDUH + (IPC or GCS)
• LMWH + (IPC or GCS)
• Fondaparinux
Major trauma w/ low to moderate risk for Any of the following would be appropriate:
bleeding • LDUH
• LMWH
B261
PATIENT AT MODERATE TO HIGH RISK FOR VTE (CONT’D)

VTE - PREVENTION

RISK FACTOR FOR VTE
Major open urologic procedures Any of the following would be appropriate:
• LDUH 8-12 hourly
• LMWH
• Fondaparinux
• GCS &/or IPC started prior to surgery & continued until
patient is ambulatory
• Combination of pharmacologic thromboprophylaxis w/
mechanical method
Laparoscopic procedures w/ additional ≥1 of the following would be appropriate:
risk factors • LDUH
• LMWH
• Fondaparinux
• GCS
• IPC
Inpatient bariatric surgery Any of the following would be appropriate:
• LMWH, higher dose for non-obese patients
• LDUH 8 hourly, higher dose for non-obese patients
• Fondaparinux
• Combination of pharmacologic thromboprophylaxis w/ IPC
Major thoracic surgery Any of the following would be appropriate:
• LMWH
• LDUH
• Fondaparinux
Coronary artery bypass surgery (CABG) Any of the following would be appropriate:
• LMWH, preferred
• LDUH
• Bilateral GCS or IPC
Elective total hip replacement (THR) Any of the following would be appropriate:
• Apixaban
• Rivaroxaban
• LMWH
- Usual high-risk dose started 12 hours pre-op or
12-24 hours post-op, or
- 4-6 hours post-op at half the usual high-risk dose the
following day
• Fondaparinux
- Started 6-24 hours post-op
• Warfarin, adjusted dose (INR target 2.5: INR range 2.0-3.0)
started pre-op or evening of the surgical day
Elective THR w/ high risk of bleeding • VFP or IPC until bleeding decreases then substitute or add
pharmacological thromboprophylaxis
Elective total knee replacement (TKR) Any of the following would be appropriate:
• Apixaban
• Rivaroxaban
• LMWH, usual high-risk dose
• Fondaparinux
Alternative:
• IPC
Not all products are available or approved for above use in all countries
B262
PATIENT AT MODERATE TO HIGH RISK FOR VTE (CONT’D)
VTE - PREVENTION
RISK FACTOR FOR VTE
Hip fracture surgery (HFS) Any of the following would be appropriate:
• Fondaparinux
• LMWH
• LDUH
Elective TKR w/ high risk of bleeding • VFP or IPC until bleeding decreases then substitute or add
HFS w/ high risk of bleeding pharmacological thromboprophylaxis
Arthroscopic knee surgery w/ additional • LMWH
risk factor or following a complicated
procedure
Critical care patients who are at Any of the following would be appropriate for moderate
moderate or higher risk risk:
• LMWH
• LDUH
For higher risk:
• LMWH
Anticoagulation contraindicated • GCS
• IPC
Duration of Prophylaxis
Medical Conditions
• The optimal length of thromboprophylaxis in medical patients is yet undetermined
• May consider giving prophylaxis for 6-21 days or until hospital discharge, whichever comes first
Major General Surgery
• 10-14 days post-surgery or for length of hospitalization
- Appropriate length of prophylaxis should be based on clinical factors (eg mobilization)
• May use an extended antithrombotic prophylaxis (>3 weeks) in patients undergoing major surgery
• For patients who have undergone major cancer surgery or have previous VTE, continue LMWH for up to
28 days after discharge
Major Gynecologic Surgery
• Continue prophylaxis until discharge
• For high-risk patients including those who have undergone major cancer surgery or have previous VTE,
continue LMWH for up to 28 days after discharge
Major Orthopedic Surgery
• At least 10-14 days post-surgery
• Extended prophylaxis for up to 35 days after THR, TKR & HFS
• Prolonged out-of-hospital prophylaxis should be considered for high-risk patients
- LMWH, Fondaparinux or adjusted-dose Warfarin may be considered for extended out-of-hospital prophylaxis
B263
Dosage Guidelines
VTE - PREVENTION

Drug Dosage Remarks
Apixaban Prevention of VTE: Adverse Reactions
2.5 mg PO 12 hrly • Hematologic effects (anemia, hemorrhage, contusion); GI
Initial dose: Given effect (nausea)
12-24 hr post-op Special Instructions
Duration: • Contraindicated in patients w/ clinically significant active
Hip replacement surgery: bleeding, hepatic disease w/ coagulopathy & clinically
32-38 days relevant bleeding risk
Knee replacement • Use w/ caution in hip fracture surgery, galactose
surgery: 10-14 days intolerance, glucose-galactose malabsorption, severe renal
Prevention of recurrent impairment, hepatic impairment
DVT &/or PE: • Discontinue use in severe hemorrhage
2.5 mg PO 12 hrly • Monitor for signs of neurological impairment
To be initiated following
completion of 6 mth
treatment for DVT/PE or
w/ another anticoagulant
Betrixaban Prevention of VTE: Adverse Reactions
Initial dose: 160 mg PO • Hematologic effects (bleeding); GI effect (nausea); Other
24 hrly effects (abnormal LFT, increased blood bilirubin &
Maintenance dose: 80 mg gamma-glutamyltransferase, rash, pruritus)
PO 24 hrly x 35-42 days Special Instructions
• Doses are to be given at the same time of the day w/ food
• Contraindicated in patients w/ clinically significant active
bleeding
• Use w/ caution in patients receiving neuraxial anesthesia
or undergoing spinal puncture as Betrixaban increases risk
for hematomas which may result in long-term or
permanent paralysis; in patients w/ an increased risk of
bleeding, severe renal impairment, mild or moderate
hepatic impairment, concomitant use of medicines
affecting hemostasis (eg Aspirin, Heparin, thrombolytic
agents, SSRIs, NSAIDs) & P-glycoprotein inhibitors (eg
Verapamil, Cyclosporin A, Yohimbine, Tamoxifen, etc)

B264
Dosage Guidelines
VTE - PREVENTION
Drug Dosage Remarks
Edoxaban Treatment of DVT & Adverse Reactions
PE & prevention of • Hematologic effects (anemia, hemorrhage); GI effect
recurrent DVT & PE: (nausea); Other effects (abnormal LFT, increased blood
60 mg PO 24 hrly bilirubin & gamma-glutamyltransferase, rash, pruritus)
following initial use of Special Instructions
parenteral anticoagulant
for at least 5 days • Edoxaban 15 mg is not indicated as monotherapy
Patients w/ moderate • Contraindicated in patients w/ clinically significant active
or severe renal bleeding or conditions at risk for major bleeding, hepatic
impairment (CrCl disease w/ coagulopathy & clinically relevant bleeding risk,
15-50 mL/min), ≤60 kg uncontrolled severe HTN, concomitant treatment w/ any
body wt, or concomitant other anticoagulants except when switching oral
use of P-gp inhibitors anticoagulant therapy or when UFH is given at doses
(Ciclosporin, necessary to maintain an open central venous or arterial
Dronedarone, catheter
Erythromycin, • Use w/ caution in patients w/ an increased risk of
Ketoconazole) are given bleeding, moderate or severe renal impairment, mild or
30 mg PO 24 hrly moderate hepatic impairment, concomitant use of
medicines affecting hemostasis
Fondaparinux Prevention of VTE in Adverse Reactions
(Fondaparin) abdominal & • Hematologic effects (hemorrhage, thrombocytopenia,
orthopedic surgery: anemia, purpura); Hepatic effect (abnormal LFT); Other
2.5 mg SC 24 hrly effect (edema)
starting 6-8 hr post-op • Less common effects: CNS effects (vertigo, dizziness,
once hemostasis has headache); CV effect (hypotension); GI effects (N/V,
been established x dyspepsia, constipation, diarrhea); Dermatologic effects
5-9 days (rash, pruritus); Rare allergic reactions
High-risk patients: Special Instructions
6-14 days
• Avoid in patients w/ clinically significant bleeding, severe
Hip fracture: Up to 32 renal impairment, w/ acute bacterial endocarditis or in
days those w/ confirmed HIT
• Use w/ caution in patients w/ an increase risk of
hemorrhage; acute GI ulcer, recent intracranial
hemorrhage, or shortly after brain, spinal or ophthalmic
surgery; use w/ caution in patients >75 yr, those weighing
<50 kg, those w/ moderate renal impairment, severe
hepatic impairment, w/ history of HIT
• Monitoring of platelets is recommended at baseline & at
the end of treatment
• Should not be given as an IM inj

B265
Dosage Guidelines
VTE - PREVENTION

Drug Dosage Remarks
Rivaroxaban Prevention of VTE in Adverse Reactions
orthopedic surgery: • Hematologic effects (hemorrhage, anemia, decreased
Initial dose: 10 mg PO 24 hrly hemoglobin); Hepatic effect (increased ALT & AST);
6-10 hr post-op & establishment CNS effects (dizziness, headache, syncope); CV effects
of hemostasis (tachycardia, hypotension); GI effect (nausea);
Duration:
Major hip surgery: 5 wk Dermatologic effects (pruritus, rashes); Other effects
Major knee surgery: 2 wk (fever, peripheral edema, postprocedural hemorrhage)
Prevention of recurrent DVT Special Instructions
& PE: • Contraindicated in patients w/ clinically significant
Days 1-21: 15 mg PO 12 hrly active bleeding, hepatic disease associated w/
Max dose: 30 mg/day coagulopathy that can lead to relevant risk of bleeding
Days 22 onwards: 20 mg PO
24 hrly • Use w/ caution in patients w/ hemorrhagic risk, lactose
Max dose: 20 mg/day or galactose intolerance, & mod-severe renal
Following completion of at impairment
least 6 mth therapy: 10-20 mg
PO 24 hrly
Max dose: 10-20 mg/day
Dabigatran Prevention of VTE in Adverse Reactions
etexilate orthopedic surgery: • Hematologic effects (hemorrhage, anemia, hematoma,
Initially 110 mg PO within thrombocytopenia); Renal effect (hematuria); GI effects
1-4 hr after completion of (dyspepsia, N/V, GI hemorrhage, abdominal pain,
surgery, then 220 mg PO 24 hrly diarrhea, gastroesophagitis, abnormal hepatic
If treatment is not started on function); Other effects (wound secretion,
the day of surgery, initial dose postprocedural discharge)
should be 220 mg PO 24 hrly Special Instructions
Duration: • Contraindicated in patients w/ severe renal impairment,
hemorrhagic manifestations, bleeding diathesis,
Elective knee replacement patients w/ spontaneous or pharmacological hemostatic
surgery: 10 days impairment, organ lesions at risk of clinically significant
Elective hip replacement bleeding (including hemorrhagic stroke within the last
surgery: 28-35 days 6 mth, patients on concomitant therapy w/ systemic
Prevention of recurrent DVT Ketoconazole, prosthetic heart valve replacement)
& PE: 150 mg PO 12 hrly • Use w/ caution in hepatic impairment, renal
following treatment w/ a insufficiency, increased hemorrhagic risk, spinal/
parenteral anticoagulant for at epidural anesthesia, lumbar puncture
least 5 days • Discontinue use in patients who develop acute renal failure
Heparin Group
Antithrombin Congenital insufficiency: Adverse Reactions
III (Human Individualized dosage • CNS effects (headache, dizziness); GI effects (foul
antithrombin) taste, nausea); Other effects (flushing, chest tightness,
Usual starting dose: 30-50 IU/ chills, cramps; rarely, hypersensitivity reactions)
kg IV Special Instructions
Max administration rate: • Concomitant use w/ heparin increases risk of bleeding;
0.08 mL/kg/min monitoring of clinical effects & coagulation tests is
recommended; dose of heparin adjusted as appropriate
• Human plasma-derived antithrombin III preparations
carry risk of viral transmission; manufacturing
processes (eg heating to about 60 degrees) have
reduced the risk of transmitting some viral infections
• Contraindicated in patients w/ goat milk or protein
hypersensitivity

B266
Dosage Guidelines
VTE - PREVENTION
Drug Dosage Remarks
Bemiparin General surgery w/ moderate risk of VTE: 2,500 IU Adverse Reactions
sodium anti-Xa SC 2 hr before or 6 hr post-op • Hematologic effects
On subsequent days: 2,500 IU anti-Xa SC 24 hrly (hemorrhage,
Orthopedic surgery w/ high VTE risk: 3,500 IU anti-Xa thrombocytopenia); Inj
SC 2 hr before or 6 hr post-op site reaction; Rarely
On subsequent days: 3,500 IU anti-Xa SC 24 hrly hypersensitivity reaction
Follow & maintain prophylactic treatment for at least 7-10 (anaphylaxis); Effects that
days post-op & until risk of thromboembolic disease has may occur w/ long-term
decreased use (osteoporosis,
Prevention of thromboembolic disease in non-surgical alopecia)
patients: 2,500 or 3,500 IU/day SC Special Instructions
Secondary prevention of VTE recurrences in patients w/
DVT & transitory risk factors: 3,500 IU/day SC up to a • Avoid in patients w/
max of 3 mth active major bleeding,
patients w/ positive
Dalteparin General surgery in moderate-risk patients: 2500 IU SC in vitro test for
sodium 1-2 hr pre-op & 2500 IU SC 24 hrly post-op x 5-7 days or antiplatelet antibody to
until patient is fully ambulant the specific heparin,
General surgery in high-risk patients: 5000 IU SC in the injury or surgery to CNS,
evening pre-op & 5000 IU SC 24 hrly in the evening post-op eyes or ears
x 5-10 days • Use w/ caution in patients
or w/ hemorrhagic disorders
2500 IU SC 1-2 hr pre-op & 2500 IU SC 8-12 hr post-op (including history of
followed by 5000 IU SC 24 hrly until patient is mobilized Heparin-induced
Orthopedic surgery (eg hip replacement): Start w/ 2500 IU thrombocytopenia),
SC 2 hr pre-op & 2500 IU SC 4-8 hr post-op then 5000 IU peptic ulcer,
SC 24 hrly x up to 35 days cerebrovascular disorders,
uncontrolled
Patients w/ restricted mobility: 5000 IU SC 24 hrly x hypertension, hepatic or
12-14 days or longer renal impairment, surgery
Danaparoid General or orthopedic surgery: 750 anti-Xa units SC at sites at risk for
sodium 12 hrly starting 1-4 hr pre-surgery & then not sooner than hemorrhage,
2 hr post-surgery hypersensitivity to
Duration: 7-10 days Heparin
• Consider risk vs benefit
Enoxaparin General surgery in moderate-risk patients: 20 mg SC 2 hr
before neuraxial
pre-op & 20 mg SC 24 hrly post-op x 7-10 days
intervention is employed
General surgery in high-risk patients (eg orthopedic in patients anticoagulated
surgery): 40 mg SC 12 hr pre-op & 40 mg SC 24 hrly or to be anticoagulated
post-op x 7-10 days, or up to 5 wk after orthopedic surgery for thromboprophylaxis
Medical conditions: 40 mg SC 24 hrly x 6-14 days, • Monitoring of platelets is
continued until return to ambulation (Please note: recommended at baseline
20 mg=2000 anti-Xa IU) & periodically during
Heparin LDUH: treatment
(Unfractionated 5000 IU SC 2-6 hr pre-op then 8-12 hrly post-op x • Should not be given as an
Heparin) 7-14 days or until patient is mobile, whichever is longer IM inj

B267
Dosage Guidelines
VTE - PREVENTION

Drug Dosage Remarks
Nadroparin General surgery: 2850 anti-Xa IU SC Adverse Reactions
calcium 24 hrly, 1st dose given 2-4 hr pre-op • Hematologic effects (hemorrhage,
Continue treatment for 7 days or until thrombocytopenia); Inj site reaction;
patient is ambulant Rarely hypersensitivity reaction
Orthopedic surgery: 38 anti-Xa IU/kg SC (anaphylaxis); Effects that may occur w/
12 hr pre-op & 12 hr post-op then long-term use (osteoporosis, alopecia)
38 anti-Xa IU/kg SC 24 hrly x 3 days Special Instructions
4th day onwards post-op: Increase to • Avoid in patients w/ active major bleeding,
57 anti-Xa IU/kg SC 24 hrly x 10 days or patients w/ positive in vitro test for
until patient is ambulant antiplatelet antibody to the specific
Medical conditions (high-risk): heparin, injury or surgery to CNS, eyes or
≤70 kg: 3800 anti-Xa IU SC 24 hrly ears
>70 kg: 5700 anti-Xa IU SC 24 hrly • Use w/ caution in patients w/ hemorrhagic
disorders (including history of
Parnaparin General surgery: 3200 anti-Xa IU SC 2 hr Heparin-induced thrombocytopenia),
sodium pre-op then 24 hrly x 7 days peptic ulcer, cerebrovascular disorders,
General surgery in high-risk patients or uncontrolled hypertension, hepatic or
orthopedic surgery: 4250 anti-Xa IU SC renal impairment, surgery at sites at risk
12 hr pre-op & 12 hr post-op followed by for hemorrhage, hypersensitivity to
another dose a day during post-op period Heparin
x 10 days • Consider risk versus benefit before
Tinzaparin General surgery in moderate-risk neuraxial intervention is employed in
sodium patients: 3500 anti-Xa IU SC 2 hr pre-op patients anticoagulated or to be
& 3500 anti-Xa IU SC 24 hrly post-op x anticoagulated for thromboprophylaxis
7-10 days • Monitoring of platelets is recommended at
General surgery in high-risk patients & baseline & periodically during treatment
for orthopedic surgery: 50 anti-Xa IU/kg • Should not be given as an IM inj
SC 2 hr pre-op & 50 anti-Xa IU/kg SC
24 hrly post-op until patient is mobilized

B268
Dosage Guidelines
VTE - PREVENTION
Drug Dosage Remarks
Platelet Aggregation Inhibitor excluding Heparin
Aspirin1 Prophylaxis against DVT: Adverse Reactions
(Acetylsalicylic 100 mg PO 24 hrly • Hematologic effects (thrombocytopenia, anemia); GI
acid) effects (gastric hemorrhage, N/V, dyspepsia); Other
effects (salicylate sensitivity, tinnitus, severe
hypoglycemia, Reye’s syndrome)
• Contraindicated in patients w/ salicylate-induced
asthma, active peptic ulcer, hemorrhagic diathesis,
severe cardiac or renal failure
• Combination w/ >15 mg/wk Methotrexate is
contraindicated
• Use w/ caution in patients w/ renal impairment,
G6PD insufficiency, flu, chickenpox, hemorrhagic
fever, GI ulceration, asthma
Warfarin Initial dose: 5-10 mg PO/IV Adverse Reactions
24 hrly x 2 days • Hemorrhage can occur even within therapeutic INR
Followed by subsequent dose levels
that should be adjusted to • Less common effects: Cholesterol embolization (skin
target INR = 2.5 (INR range necrosis & purple discoloration of the toes); GI effects
2.0-3.0) (N/V, diarrhea); Other effects (alopecia, skin reactions,
Maintenance dose: 2-10 mg/ hepatic dysfunction, pancreatitis, jaundice, fever)
day Special Instructions
• Patients should be counseled on the risks of therapy
along w/ drug & food interactions
• Avoid in patients w/ active or at risk of hemorrhage,
PUD, severe wounds, cerebrovascular disorders &
bacterial endocarditis
• Use w/ extreme caution or not at all in those w/
severe renal or hepatic impairment
• INR monitoring is usually performed daily until the
therapeutic range (2.0-3.0) has been achieved
- Then INR is monitored 2-3x/wk for 2 wk
- Then INR is monitored wkly or less often
depending on the stability of INR

B269
References
Acute Coronary Syndromes w/out College of Cardiology/American Heart Association Joint
Committee on clinical practice guidelines. Circulation. 2021
Persistent ST-Segment Elevation Nov;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029.
Accessed 18 Dec 2021. PMID: 34709879.
Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing Hamm CW, Bassand JP, Agewall S, et al, The Task Force for the
the metabolic syndrome: a joint interim statement of the management of acute coronary syndromes (ACS) in patients
International Diabetes Federation Task Force on Epidemiolo- presenting without persistent ST-segment elevation of the
gy and Prevention, National Heart, Lung and Blood Institute, European Society of Cardiology (ESC). ESC Guidelines for
American Heart Association, World Heart Federation, the management of acute coronary syndromes in patients
International Atherosclerosis Society and International presenting without persistent ST-segment elevation. Eur
Association for the Study of Obesity. Circulation. 2009 Heart J. 2011 Dec;32(23):2999-3054. doi: 10.1093/eurheartj/
Oct;120(16):1640-1645. http://www.circ.ahajournals.org/. doi: ehr236. PMID: 21873419.
10.1161/CIRCULATIONAHA.109.192644. PMID: 19805654.
Harrington RA, Becker RC, Cannon CP, et al. Antithrombotic
American Heart Association. Part 8: Stabilization of the therapy for non-ST-segment elevation acute coronary
patient with acute coronary syndromes. Circulation. syndromes: American College of Chest Physicians evidence-
2005 Nov;112:IV-89-IV-110. https://doi.org/10.1161/ based clinical practice guidelines (8th edition). Chest. 2008
CIRCULATIONAHA.105.166561. Jun;133(Suppl 6):670S-707S. doi: 10.1378/chest.08-0691.
Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ PMID: 18574276.
ACC guideline for the management of patients with non- Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA
ST-elevation acute coronary syndromes: a report of the focused update of the guideline for the management of
American College of Cardiology/American Heart Association patients with unstable angina/non-ST elevation myocardial
Task Force on Practice Guidelines. J AM Coll Cardiol. infarction (updating the 2007 guideline and replacing the
2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017. 2011 focused update): a report of the American College
PMID: 25260718. of Cardiology Foundation/American Heart Association
Anderson JL, Adams CD, Hochman JS, et al. ACC/AHA Task Force on Practice Guidelines. J AM Coll Cardiol. 2012
2007 guidelines for the management of patients with Aug;60(7):645-681. doi: 10.1016/j.jacc.2012.06.004. PMID:
unstable angina/non-ST-Elevation myocardial infarction: 22809746.
a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. J Kleinman ME, Brennan EE, Goldberger ZD, et al. Part 5: Adult
Am Coll Cardiol. 2007 Aug;50(7):e1-e157. doi: 10.1016/j. basic life support and cardiopulmonary resuscitation quality:
jacc.2007.02.013. PMID: 17692738. 2015 American Heart Association guidelines update for
cardiopulmonary resuscitation and emergency cardiovascular
Angina. Heart and Stroke Foundation of Canada. https://www. care. Circulation. 2015 Nov;132(18)(Suppl 2):S414-S435. doi:
heartandstroke.ca. 2022. Accessed 21 Feb 2022. 10.1161/CIR.0000000000000259. PMID: 26472993.
Bertrand ME, Simoons ML, Fox KA, et al; Task Force on the
Management of Acute Coronary Syndromes of the European Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused updates:
Society of Cardiology. Management of acute coronary ACC/AHA guidelines for the management of patients
syndromes in patients presenting without persistent ST- with ST-elevation myocardial infarction (updating the
segment elevation. Eur Heart J. 2002 Dec;23(23):1809-1840. 2004 guideline and 2007 focused update) and ACC/AHA/
doi: 10.1053/euhj.2002.3385. PMID: 12503543. SCAI guidelines on percutaneous coronary intervention
(updating the 2005 guideline and 2007 focused update): a
Braunwald E, Zipes DP, Libby P. Unstable angina. Heart Disease: report of the American College of Cardiology Foundation/
A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia: American Heart Association Task Force on Practice
W.B. Saunders Company; 2001:1232-1255. Guidelines. Circulation. 2009 Dec;120(22):2271-2306. doi:
Braunwald E. Application of current guidelines to the 10.1161/CIRCULATIONAHA.109.192663. PMID: 19923169.
management of unstable angina and non-ST-elevation
Levine GN, Bates ER, Bittl JA, et al; Focused Update Writing
myocardial infarction. Circulation. 2003 Oct;108(16)(Suppl
Group. 2016 ACC/AHA guideline focused update on duration
1):III28-37. doi: 10.1161/01.CIR.0000086952.14979.32.
of dual antiplatelet therapy in patients with coronary artery
PMID: 14605017.
disease: a report of the American College of Cardiology/
Collet JP, Thiele H, Barbato E, et al. 2020 ESC guidelines for American Heart Association Task Force on Clinical Practice
the management of acute coronary syndromes in patients Guidelines. J Am Coll Cardiol. 2016 Mar 23:pii: S0735-
presenting without persistent ST-segment elevation. 29 Aug 1097(16)01699-5. doi: 10.1016/j.jacc.2016.03.513. PMID:
2020. doi: 10.1093/eurheartj/ehaa575. Accessed 01 Sep 2020. 27036918.
PMID: 32860058.
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines
Corrales-Medina VF, Madjid M, Musher DM. Role of acute
for the management of dyslipidaemias: lipid modification to
infection in triggering acute coronary syndromes. Lancet
reduce cardiovascular risk. ESC. http://www.escardio.org. 31
Infect Dis. 2010 Feb;10(2):83-92. doi: 10.1016/S1473-
Aug 2019. Accessed 09 Sep 2019.
3099(09)70331-7. PMID: 20113977.
Fifth Organization to Assess Strategies in Acute Ischemic McCann CJ, Glover BM, Menown IB, et al. Prognostic value of
Syndromes Investigators, Yusuf S, Mehta SR, et al. a multimarker approach for patients presenting to hospital
Comparison of fondaparinux and enoxaparin in acute with acute chest pain. Am J Cardiol. 2009 Jan;103(1):22-28.
coronary syndromes. N Engl J Med. 2006 Apr 6;354(14):1464- doi: 10.1016/j.amjcard.2008.08.026. PMID: 19101224.
1476. doi: 10.1056/NEJMoa055443. PMID: 16537663. Ministry of Health Malaysia, Academy of Medicine Malaysia,
Ghias S. Utility of CT coronary angiography in non-ST National Heart Association of Malaysia. Clinical practice
elevation acute coronary syndrome. British Cardiovascular guidelines of stable coronary artery disease 2018. 2nd ed.
Society. https://www.britishcardiovascularsociety.org. 2020. Academy of Medicine of Malaysia. http://www.acadmed.org.
Accessed 21 Feb 2022. my. Accessed 29 Jan 2019.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/ Ministry of Health Malaysia, National Heart Association of
CHEST/SAEM/SCCT/SCMR guideline for the evaluation Malaysia, Academy of Medicine Malaysia. Clinical practice
and diagnosis of chest pain. A report of the American guidelines on management of unstable angina/non ST
270
elevation myocardial infarction (UA/NSTEMI). Academy Eur Heart J. 2010 Aug;31:2197-2206. doi: 10.1093/eurheartj/
of Medicine of Malaysia. http://www.moh.gov.my/. 2012. ehq251. PMID: 20685679.
Ministry of Health Malaysia, National Heart Association of Valgimigli M, Bueno H, Byrne RA, et al; ESC Scientific
Malaysia, Academy of Medicine Malaysia. Management of Document Group; ESC Committee for Practice Guidelines
non-ST elevation myocardial infarction (NSTE-ACS). 3rd (CPG); ESC National Cardiac Societies. 2017 ESC focused
ed. National Heart Association of Malaysia. https://www. update on dual antiplatelet therapy in coronary artery disease
malaysianheart.org. 17 Sep 2021. Accessed 21 Feb 2022. developed in collaboration with EACTS: The Task Force for
National Institute for Health and Care Excellence (NICE). Acute dual antiplatelet therapy in coronary artery disease of the
coronary syndromes. NICE. https://www.nice.org.uk. 18 Nov European Society of Cardiology (ESC) and of the European
2020. Accessed 18 Dec 2021. Association for Cardio-Thoracic Surgery (EACTS). Eur Heart
O’Connor RE, Brady W, Brooks SC, et al. Part 10: acute coronary J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419.
syndromes: 2010 American Heart Association guidelines for Accessed 15 Jan 2018. PMID: 28886622.
cardiopulmonary resuscitation and emergency cardiovascular Visseren FLJ, Mach F, Smulders YM, et al; ESC National
care. Circulation. 2010 Nov;122(18)(Suppl 3):S787-S817. doi: Cardiac Societies, ESC Scientific Document Group. 2021
10.1161/CIRCULATIONAHA.110.971028. PMID: 20956226. ESC Guidelines on cardiovascular disease prevention in
Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337.
ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate use criteria doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021.
for coronary revascularization in patients with acute coronary PMID: 34458905.
REFERENCES
syndromes: a report of the American College of Cardiology Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/
Appropriate Use Criteria Task Force, American Association AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/
for Thoracic Surgery, American Heart Association, American PCNA guideline for the prevention, detection, evaluation,
Society of Echocardiography, American Society of Nuclear and management of high blood pressure in adults: a report
Cardiology, Society for Cardiovascular Angiography of the American College of Cardiology/American Heart
and Interventions, Society of Cardiovascular Computed Association Task Force on Clinical Practice Guidelines. J Am
Tomography, and the Society of Thoracic Surgeons. J Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j.
Am Coll Cardiol. 2017 Feb;69(5):570-591. doi: 10.1016/j. jacc.2017.11.006. PMID: 29146535.
jacc.2016.10.034. PMID: 28012615. Wiviott SD, Braunwald E, McCabe CH, et al; TRITON-TIMI
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia 38 Investigators. Prasugrel versus clopidogrel in patients
(PERKI). Pedoman Tatalaksana Sindrom Koroner Akut. Edisi with acute coronary syndromes. N Engl J Med. 2007
Ketiga. Jakarta; 2014. Nov;357(20):2001-2015. doi: 10.1056/NEJMoa0706482.
Philippine Heart Association CAD Guidelines Writing PMID: 17982182.
Committee. 2014 PHA clinical practice guidelines for the
diagnosis and management of patients with coronary artery
disease. Philippine Heart Association. http://www.philheart.
org/. 27 Nov 2014.
Cardiovascular Disease Prevention
Rodriguez F, Mahaffey KW. Management of patients with
NSTE-ACS: a comparison of the recent AHA/ACC and ESC American Diabetes Association. Standards of medical care in
guidelines. J Am Coll Cardiol. 2016 Jul 19;68(3):313-21. doi: diabetes - 2013. Diabetes Care. 2013 Jan;36(Suppl 1):S11-S66.
10.1016/j.jacc.2016.03.599. PMID: 27417010. doi: 10.2337/dc13-S011. PMID: 23264422.
Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian
the management of acute coronary syndromes in patients Cardiovascular Society guidelines for the management of
presenting without persistent ST-segment elevation – web dyslipidemia for the prevention of cardiovascular disease in
addenda: Task Force for the Management of Acute Coronary the adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi:
Syndromes in Patients Presenting without Persistent ST- 10.1016/j.cjca.2016.07.510. PMID: 27712954.
Segment Elevation of the European Society of Cardiology Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/
(ESC). European Society of Cardiology. https://www.escardio. AHA guideline on the primary prevention of cardiovascular
org/. 2015. disease: a report of the American College of Cardiology/
Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for American Heart Association Task Force on Clinical Practice
the management of acute coronary syndromes in patients Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi:
presenting without persistent ST-segment elevation: Task 10.1161/CIR.0000000000000678. Accessed 18 Mar 2019.
Force for the Management of Acute Coronary Syndromes in PMID: 30879355.
Patients Presenting without Persistent ST-Segment Elevation
of the European Society of Cardiology (ESC). Eur Heart J. British Cardiac Society; British Hypertension Society;
2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Diabetes UK; HEART UK; Primary Care Cardiovascular
PMID: 26320110. Society; Stroke Association. JBS 2: Joint British Societies’
guidelines on prevention of cardiovascular disease in clinical
Spinler S. Evolution of antithrombotic therapy used in
practice. Heart. 2005 Dec;91(Suppl 5):v1-v52. doi: 10.1136/
acute coronary syndromes. Cardiology. http://www.circ.
hrt.2005.079988. PMID: 16365341.
ahajournals.org.
Tan JWC, Lam CSP, Kasim SS, et al. Asia-Pacific consensus Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention
statement on the optimal use of high-sensitivity troponin of cardiovascular diseases in people with diabetes mellitus:
assays in acute coronary syndromes diagnosis: focus a scientific statement from the American Heart Association
on hs-TnI. Heart Asia. 2017;9(1):81-87. doi: 10.1136/ and the American Diabetes Association. Diabetes Care. 2007
heartasia-2016-010818. Jan;30(1):162-172. doi: 10.2337/dc07-9917. PMID: 17192355.
Task Force on Myocardial Revascularization of the European Centers for Disease Control and Prevention (CDC). People
Society of Cardiology (ESC) and the European Association for with certain medical conditions. CDC. https://www.cdc.gov/
Cardio-Thoracic Surgery (EACTS); European Association for coronavirus/2019-ncov. 03 Feb 2021. Accessed 22 Feb 2021.
Percutaneous Cardiovascular Interventions (EAPCI), Wijns Cheung BM, Cheng CH, Lau CP, et al. 2016 Consensus
W, Kolh P, et al. Guidelines on myocardial revascularization. statement on prevention of atherosclerotic cardiovascular
Eur Heart J. 2010 Oct;31(20):2501-2555. doi: 10.1093/ disease in the Hong Kong population. Hong Kong Med J.
eurheartj/ehq277. PMID: 20802248. 2017 Apr;23(2):191-201. doi: 10.12809/hkmj165045. PMID:
Thygesen K, Mair J, Katus H, et al. Recommendations for the 28387202.
use of cardiac troponin measurement in acute cardiac care.
271
Clerkin KJ, Fried JA, Raikhelkar J, et al. COVID-19 and and prevention of atherosclerosis. Endocr Pract. 2012
cardiovascular disease. Circulation. 2020 May 19;141(20):1648- Mar;18(Suppl 1):1-78. https://www.ncbi.nlm.nih.gov. PMID:
1655. doi: 10.1161/CIRCULATIONAHA.120.046941. 22522068.
Accessed 22 Feb 2021. PMID: 32200663. Jensen MD, Ryan DH, Apovian CM, et al; American College
Corrales-Medina VF, Suh KN, Rose G, et al. Cardiac of Cardiology/American Heart Association Task Force on
complications in patients with community-acquired Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS
pneumonia: a systematic review and meta-analysis of guideline for the management of overweight and obesity
observational studies. PLoS Med. 2011 Jun;8(6):e1001048. doi: in adults: a report of the American College of Cardiology/
10.1371/journal.pmed.1001048. PMID: 21738449. American Heart Association Task Force on Practice
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC guidelines on Guidelines and The Obesity Society. Nov 12, 2013. J Am Coll
diabetes, pre-diabetes, and cardiovascular diseases developed Cardiol. 2014 Jul;63(Suppl 25 Pt B):2985-3023. doi: 10.1016/j.
in collaboration with the EASD. ESC. http://www.escardio. jacc.2013.11.004. PMID: 24239920.
org. 31 Aug 2019. Accessed 10 Sep 2019. Lackland DT, Elkind MS, D’Agostino R Sr, et al; American
Das SR, Everett BM, Birtcher KK, et al. 2018 ACC expert Heart Association Stroke Council; Council on Epidemiology
consensus decision pathway on novel therapies for and Prevention; Council on Cardiovascular Radiology and
cardiovascular risk reduction in patients with type 2 Intervention; Council on Cardiovascular Nursing; Council
diabetes and atherosclerotic cardiovascular disease: a report on Peripheral Vascular Disease. Inclusion of stroke in
of the American College of Cardiology Task Force on Expert cardiovascular risk prediction instruments: a statement
REFERENCES
Consensus Decision Pathways. J Am Coll Cardiol. 2018 for healthcare professionals from the American Heart
Dec 18;72(24):3200-3223. doi: 10.1016/j.jacc.2018.09.020. Association/American Stroke Association. Stroke. 2012
Accessed 19 Feb 2019. PMID: 30497881. Jul;43(7):1998-2027. doi: 10.1161/STR.0b013e31825bcdac.
Dehghan M, Mente A, Zhang X, et al; Prospective Urban Rural PMID: 22627990.
Epidemiology (PURE) study investigators. Associations Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes
of fats and carbohydrate intake with cardiovascular mellitus: from pathophysiology to clinical management. Nat
disease and mortality in 18 countries from five continents Rev Endocrinol. 2021 Jan;17(1):11-30. doi: 10.1038/s41574-
(PURE): a prospective cohort study. Lancet. 2017 Nov 020-00435-4. Accessed 22 Feb 2021. PMID: 33188364.
4;390(10107):2050-2062. doi: 10.1016/S0140-6736(17)32252- Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC
3. PMID: 28864332. expert consensus decision pathway on the role of non-statin
Doupis J, Avramidis K. Managing diabetes during the therapies for LDL-cholesterol lowering in the management
COVID-19 pandemic. Eur Endocrinol. 2020 Oct;16(2):85–87. of atherosclerotic cardiovascular disease risk: a report of the
doi: 10.17925/EE.2020.16.2.85. Accessed 22 Feb 2021. PMID: American College of Cardiology Task Force on clinical expert
33117436. consensus documents. J Am Coll Cardiol. 2016 Jul;68(1):92-
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al; American College 125. doi: 10.1016/j.jacc.2016.03.519. PMID: 27046161.
of Cardiology/American Heart Association Task Force Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines
on Practice Guidelines. 2013 ACC/AHA guideline on the for the management of dyslipidaemias: lipid modification to
assessment of cardiovascular risk: a report of the American reduce cardiovascular risk. ESC. http://www.escardio.org. 31
College of Cardiology/American Heart Association Task Aug 2019. Accessed 09 Sep 2019.
Force on Practice Guidelines. Circulation. 2014 Jun;129(25 McDonagh TA, Metra M, Adamo M, et al; ESC Scientific
Suppl 2):S49-S73. doi: 10.1161/01.cir.0000437741.48606.98. Document Group. 2021 ESC guidelines for the diagnosis and
PMID: 24222018. treatment of acute and chronic heart failure. Eur Heart J. 2021
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/ Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368.
AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/ Accessed 15 Dec 2021. PMID: 34447992.
NLA/PCNA guideline on the management of blood Medical Services Commission. Cardiovascular disease - primary
cholesterol: executive summary: a report of the American prevention. Toronto (ON); 2008 Mar:001-018.
College of Cardiology/American Heart Association Task Mekaj YH, Mekaj AY, Duci SB, et al. New oral anticoagulants:
Force on Clinical Practice Guidelines. J Am Coll Cardiol. their advantages and disadvantages compared with vitamin K
2019 Jun 25;73(24):3168-3209. doi: 10.1016/j.jacc.2018.11.002. antagonists in the prevention and treatment of patients with
Accessed 29 Jan 2019. PMID: 30423391.
thromboembolic events. Ther Clin Risk Manag. 2015 Jun
International Task Force for Prevention of Coronary Heart 24;11:967-977. doi: 10.2147/TCRM.S84210. PMID: 26150723.
Disease & International Atherosclerosis Society. Pocket
guide to prevention of coronary heart disease. Germany; Ministry of Health Malaysia, Academy of Medicine Malaysia
2003 Jan:001-128. and National Heart Association of Malaysia. Clinical
Iqbal Z, Ho JH, Adam S, et al. Managing hyperlipidaemia practice guidelines on primary & secondary prevention of
in patients with COVID-19 and during its pandemic: cardiovascular disease 2017. Academy of Medicine Malaysia.
an expert panel position statement from HEART UK. http://www.acadmed.org.my. 2017.
Atherosclerosis. 2020 Nov;313:126-136. doi: 10.1016/j. Ministry of Health Malaysia. Prevention of cardiovascular
atherosclerosis.2020.09.008. Accessed 22 Feb 2021. PMID: disease in women 2016. 2nd ed. Ministry of Health Malaysia.
33045618. http://www.moh.gov.my. 2016.
Ishigami J, Kou M, Ding N, et al. Cardiovascular disease and Ministry of Health Malaysia. Prevention of cardiovascular
coronavirus disease 2019: epidemiology, management, and
disease in women. Academy of Medicine Malaysia. http://
prevention. Curr Epidemiol Rep. 2021 Jan 02;1-8. doi: 10.1007/
s40471-020-00261-2. Accessed 22 Feb 2021. PMID: 33425654. www.acadmed.org.my. 2008.
Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Ministry of Health Singapore. Screening for cardiovascular
Association of Clinical Endocrinologists and American disease and risk factors. MOH (Singapore). http://www.
College of Endocrinology guidelines for management of moh.gov.sg/. 2011.
dyslipidemia and prevention of cardiovascular disease. Endocr Musher DM, Rueda AM, Kaka AS, et al. The association between
Pract. 2017 Apr;23(Suppl 2):1-87. doi: 10.4158/EP171764. pneumococcal pneumonia and acute cardiac events. Clin
APPGL. PMID: 28437620. Infect Dis. 2007 Jul 15;45(2):158-165. doi: 10.1086/518849.
Jellinger PS, Smith DA, Mehta AE, et al; AACE Task PMID: 17578773.
Force for Management of Dyslipidemia and Prevention New Zealand Guidelines Group, National Heart Foundation
of Atherosclerosis. American Association of Clinical
Endocrinologists’ guidelines for management of dyslipidemia of New Zealand & Stroke Foundation of New Zealand.
The assessment and management of cardiovascular risk.
272
Ministry of Health - Manatū Hauora. http://www.health. Council on Clinical Cardiology. Omega-3 polyunsaturated
govt.nz/. Dec 2003. fatty acid (Fish Oil) supplementation and the prevention
Noncommunicable Diseases and Mental Health, World Health of clinical cardiovascular disease: a science advisory from
Organization. Integrated management of cardiovascular the American Heart Association. Circulation. 2017 Apr
risk. Report of WHO meeting, Geneva. http://whqlibdoc. 11;135(15):e867-e884. doi: 10.1161/CIR.0000000000000482.
who.int/. Jul 2012. PMID: 28289069.
Smith SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF
O’Keefe JH, Carter MD, Lavie CJ. Primary and secondary
Secondary prevention and risk reduction therapy for
prevention of cardiovascular diseases: a practical evidence-
patients with coronary and other atherosclerotic vascular
based approach. Mayo Clin Proc. 2009 Aug;84(8):741-757. doi:
disease: 2011 update: a guideline from the American Heart
10.1016/S0025-6196(11)60525-9. PMID: 19648392. Association and American College of Cardiology Foundation.
Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for Circulation. 2011 Nov;124(22):2458-2473. doi: 10.1161/
primary prevention of cardiovascular disease and stroke: CIR.0b013e318235eb4d. PMID: 22052934.
2002 update: consensus panel guide to comprehensive Stefan N, Birkenfeld AL, Schulze MB. Global pandemics
risk reduction for adult patients without coronary or interconnected - obesity, impaired metabolic health and
other atherosclerotic vascular diseases. American Heart COVID-19. Nat Rev Endocrinol. 2021 Mar;17(3):135-149.
Association Science Advisory and Coordinating Committee. doi: 10.1038/s41574-020-00462-1. Accessed 22 Feb 2021.
Circulation. 2002 Jul;160(3):388-391. doi: 10.1161/01. PMID: 33479538.
REFERENCES
cir.0000020190.45892.75. PMID: 12119259. Stewart J, Manmathan G, Wilkinson P. Primary prevention of
Perk J, De Backer G, Gohlke H, et al; European Association cardiovascular disease: a review of contemporary guidance
for Cardiovascular Prevention & Rehabilitation (EACPR); and literature. JRSM Cardiovasc Dis. 2017;6:1-9. doi:
ESC Committee for Practice Guidelines (CPG). European 10.1177/2048004016687211. Accessed 09 May 2018. PMID:
guidelines on cardiovascular disease prevention in clinical 28286646.
practice (version 2012). The Fifth Joint Task Force of the Stone NJ, Robinson JG, Lichtenstein AH, et al; American
European Society of Cardiology and Other Societies on College of Cardiology/American Heart Association Task
Cardiovascular Disease Prevention in Clinical Practice Force on Practice Guidelines. 2013 ACC/AHA guideline on
(constituted by representatives of nine societies and by invited the treatment of blood cholesterol to reduce atherosclerotic
experts). Eur Heart J. 2012 Jul;33(13):1635-1701. doi: 10.1093/ cardiovascular risk in adults: a report of the American
eurheartj/ehs092. PMID: 22555213. College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation. 2014 Jun;129(25
Piepoli MF, Hoes AW, Agewall S, et al; Authors/Task Force Suppl 2):S1-S45. doi: 10.1161/01.cir.0000437738.63853.7a.
Members. 2016 European guidelines on cardiovascular PMID: 24222016.
disease prevention in clinical practice: The Sixth Joint Task
St-Onge MP, Ard J, Baskin ML, et al; American Heart
Force of the European Society of Cardiology and Other
Association Obesity Committee of the Council on Lifestyle
Societies on Cardiovascular Disease Prevention in Clinical and Cardiometabolic Health; Council on Cardiovascular
Practice (constituted by representatives of 10 societies and Disease in the Young; Council on Clinical Cardiology; and
by invited experts) developed with the special contribution Stroke Council. Meal timing and frequency: implications
of the European Association for Cardiovascular Prevention & for cardiovascular disease prevention: a scientific statement
Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315- from the American Heart Association. Circulation. 2017
2381.doi: 10.1093/eurheartj/ehw106. PMID: 27222591. Feb;135(9):e96-e121. doi: 10.1161/CIR.0000000000000476.
Redberg RF, Benjamin EJ, Bittner V, et al; American PMID: 28137935.
Academy of Family Physicians; American Association of Task Force for the management of COVID-19 of the European
Cardiovascular and Pulmonary Rehabilitation; Preventive Society of Cardiology. ESC guidance for the diagnosis and
Cardiovascular Nurses Association. AHA/ACCF [corrected] management of cardiovascular disease during the COVID-19
2009 performance measures for primary prevention of pandemic: part 2-care pathways, treatment, and follow-up.
cardiovascular disease in adults: a report of the American Eur Heart J. 2021 Nov 16;ehab697. doi: 10.1093/eurheartj/
College of Cardiology Foundation/American Heart ehab697. Accessed 14 Jan 2022. PMID: 34791154.
Association task force on performance measures (writing
The European Society for Cardiology (ESC). ESC guidance
committee to develop performance measures for primary
for the diagnosis and management of CV disease during the
prevention of cardiovascular disease): developed in
COVID-19 pandemic. ESC. https://www.escardio.org. 10 June
collaboration with the American Academy of Family
2020. Accessed 22 Feb 2021.
Physicians; American Association of Cardiovascular and
Pulmonary Rehabilitation; and Preventive Cardiovascular U.S. Preventive Services Task Force. Aspirin for the prevention
Nurses Association: endorsed by the American College of cardiovascular disease: U.S. Preventive Services Task
of Preventive Medicine, American College of Sports Force recommendation statement. Ann Intern Med. 2009
Medicine, and Society for Women’s Health Research. Mar;150(6):396-404. doi: 10.7326/0003-4819-150-6-
Circulation. 2009 Sep;120(13):1296-1336. doi: 10.1161/ 200903170-00008. PMID: 19293072.
CIRCULATIONAHA.109.192617. PMID: 19770388. Visseren FLJ, Mach F, Smulders YM, et al; ESC National
Cardiac Societies, ESC Scientific Document Group. 2021
Scottish Intercollegiate Guidelines Network. Management of
ESC guidelines on cardiovascular disease prevention in
obesity. SIGN. http://www.sign.ac.uk. Feb 2010. clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337.
Siriwardena AN, Gwini SM, Coupland CA . Influenza doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021.
vaccination, pneumococcal vaccination and risk of acute PMID: 34458905.
myocardial infarction: matched case-control study. CMAJ. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/
2010 Oct;182(15):1617-1623. doi: 10.1503/cmaj.091819. AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/
PMID: 20855479. PCNA guideline for the prevention, detection, evaluation,
Siscovick DS, Barringer TA, Fretts AM, et al; American Heart and management of high blood pressure in adults: a report
Association Nutrition Committee of the Council on Lifestyle of the American College of Cardiology/American Heart
and Cardiometabolic Health; Council on Epidemiology Association Task Force on Clinical Practice Guidelines. J Am
and Prevention; Council on Cardiovascular Disease in the Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j.
jacc.2017.11.006. PMID: 29146535.
Young; Council on Cardiovascular and Stroke Nursing; and
273
Wood D, De Backer G, Faergeman O, et al. Prevention of patients with chronic stable angina: a report of the American
coronary heart disease in clinical practice. Recommendations College of Cardiology/American Heart Association Task
of the Second Joint Task Force of European and other Societies Force on Practice Guidelines Writing Group to Develop the
on coronary prevention. Eur Heart J. 1998 Oct;19(10):1434- Focused Update of the 2002 guidelines for the management
1503. doi: 10.1053/euhj.1998.1243. PMID: 9820987. of patients with chronic stable angina. J Am Coll Cardiol.
World Health Organization. Prevention of cardiovascular 2007 Dec;50(23):2264-2274. doi: 10.1016/j.jacc.2007.08.002.
disease: guidelines for assessment and management of PMID: 18061078.
cardiovascular risk. WHO. http://whqlibdoc.who.int/. 2007. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC guidelines
on cardiac pacing and cardiac resynchronization therapy. Eur
Heart J. 2021 Sep;42(35):3427-3520. doi: 10.1093/eurheartj/
Chronic Coronary Syndromes ehab364. Accessed 10 Jan 2022. PMID: 34455430.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/
CHEST/SAEM/SCCT/SCMR guideline for the evaluation
Abrams J, Thadani U. Therapy of stable angina pec- and diagnosis of chest pain. A report of the American
toris: the uncomplicated patient. Circulation. 2005 College of Cardiology/American Heart Association Joint
Oct;112(15):e255-e259. https://doi.org/10.1161/CIRCULA- Committee on clinical practice guidelines. Circulation. 2021
TIONAHA.104.526699. PMID: 16216965. Nov;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029.
Abrams J. Chronic stable angina. N Engl J Med. 2005 Accessed 18 Dec 2021. PMID: 34709879.
REFERENCES
Jun;352(24):2524-2533. doi: 10.1056/NEJMcp042317. PMID: Jellinger PS, Handelsman Y, Rosenblit PD, et al. American
15958808. Association of Clinical Endocrinologists and American
Begg A, Cargill R. Management of stable angina: a national College of Endocrinology guidelines for management of
clinical guideline. Scottish Intercollegiate Guidelines dyslipidemia and prevention of cardiovascular disease. Endocr
Network. http://www.sign.ac.uk/. Feb 2007. Pract. 2017 Apr;23(Suppl 2):1-87. doi: 10.4158/EP171764.
Cheshire and Merseyside Cardiac Network, North Wales APPGL. PMID: 28437620.
Cardiology. Guidelines on the diagnosis and management Joseph J, Velasco A, Hage FG, et al. Guidelines in review:
of stable angina. Midlands and Lancashire Commissioning Comparison of ESC and ACC/AHA guidelines for the
Support Unit. http://mm.wirral.nhs.uk. Nov 2007. diagnosis and management of patients with stable coronary
Daud AM, Ghapar AK, Teh B, et al. Clinical practice guidelines: artery disease. J Nucl Cardiol. 2018 Apr;25(2):509-515. doi:
management of stable angina pectoris. National Heart 10.1007/s12350-017-1055-0. Accessed 11 Feb 2019. PMID:
Association of Malaysia, Academy of Malaysia, and Ministry 28884447.
of Health Malaysia. 2010 Jul:001-78. Kannam JP, Aroesty JM, Gersh BJ. Chronic coronary syndrome:
Dehghan M, Mente A, Zhang X, et al; Prospective Urban Rural Overview of care. UpToDate. https://www.uptodate.com. Aug
Epidemiology (PURE) study investigators. Associations of 2020. Accessed 22 Sep 2020.
fats and carbohydrate intake with cardiovascular disease Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the
and mortality in 18 countries from five continents (PURE): diagnosis and management of chronic coronary syndromes:
a prospective cohort study. Lancet. 2017 Aug 28:pii: S0140- The Task Force for the diagnosis and management of chronic
6736(17)32252-3. doi: 10.1016/S0140-6736(17)32252-3. coronary syndromes of the European Society of Cardiology
PMID: 28864332. (ESC). Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/
Elwood PC, Morgan G, Woollard M, et al. ‘Time is muscle’: eurheartj/ehz425. Accessed 10 Sep 2019. PMID: 31504439.
aspirin taken during acute coronary thrombosis. Br J Cardiol. Kurdi H. Chronic coronary syndrome – a new era for the
2010 Jul;17:185-189. https://bjcardio.co.uk. Accessed 04 diagnosis and management of stable coronary artery
Jul 2018. disease? British Cardiovascular Society. https://www.
Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/ britishcardiovascularsociety.org. 2020. Accessed 22 Sep 2020.
AATS/PCNA/SCAI/STS focused update of the guideline Leong DP, McMurray JJV, Joseph PG, et al. From ACE
for the diagnosis and management of patients with stable inhibitors/ARBs to ARNIs in coronary artery disease
ischemic heart disease: a report of the American College and heart failure (part 2/5). J Am Coll Cardiol. 2019 Aug
of Cardiology/American Heart Association Task Force 6;74(5):683-698. doi: 10.1016/j.jacc.2019.04.068. Accessed
on Practice Guidelines, and the American Association 23 Feb 2022. PMID: 31370961.
for Thoracic Surgery, Preventive Cardiovascular Nurses Levine T, Aroesty JM. Stable ischemic heart disease: indications
Association, Society for Cardiovascular Angiography for revascularization. UpToDate. https://www.uptodate.
and Interventions, and Society of Thoracic Surgeons. com. Feb 2016.
Circulation. 2014 Nov;130:1749-1767. doi: 10.1161/ Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines
CIR.0000000000000095. PMID: 25070666. for the management of dyslipidaemias: lipid modification to
Fihn SD, Gardin JM, Abrams J, et al; American College of reduce cardiovascular risk. ESC. http://www.escardio.org. 31
Cardiology Foundation/American Heart Association Task Aug 2019. Accessed 09 Sep 2019.
Force. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Ministry of Health Malaysia, Academy of Medicine Malaysia,
guideline for the diagnosis and management of patients with National Heart Association of Malaysia. Clinical practice
stable ischemic heart disease: a report of the American College guidelines of stable coronary artery disease 2018. 2nd ed.
of Cardiology Foundation/American Heart Association Task Academy of Medicine of Malaysia. http://www.acadmed.org.
Force on Practice Guidelines, and the American College my. Accessed 29 Jan 2019.
of Physicians, American Association for Thoracic Surgery,
Preventive Cardiovascular Nurses Association, Society for Mishra S, Ray S, Dalal JJ, et al. Management standards for
Cardiovascular Angiography and Interventions, and Society of stable coronary artery disease in India. Indian Heart J. 2016
Thoracic Surgeons. Circulation. 2012 Dec;126(25):e354-e471. Dec;68(Suppl 3):S31–S49. doi: 10.1016/j.ihj.2016.11.320.
doi: 10.1161/CIR.0b013e318277d6a0. PMID: 23166211. Accessed 04 Jul 2018. PMID: 28038722.
Fox K, Garcia MA, Ardissino D, et al. Guidelines on the National Institute for Health and Care Excellence (NICE). Acute
management of stable angina pectoris: executive summary: coronary syndromes. NICE. https://www.nice.org.uk. 18 Nov
The Task Force on the Management of Stable Angina Pectoris 2020. Accessed 18 Dec 2021.
of the European Society of Cardiology. Eur Heart J. 2006 Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/
Jun;27(11):1341-1381. doi: 10.1093/eurheartj/ehl001. PMID: ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria
16735367. for coronary revascularization in patients with stable ischemic
Fraker TD, Fihn SD, et al. 2007 chronic angina focused update heart disease: a report of the American College of Cardiology
of the ACC/AHA 2002 guidelines for the management of Appropriate Use Criteria Task Force, American Association
for Thoracic Surgery, American Heart Association, American
274
Society of Echocardiography, American Society of Nuclear Baldassarre D, Franceschini G, Peruzzotti G, et al. Clinical
Cardiology, Society for Cardiovascular Angiography evaluation of probucol in hypercholesterolemia: individual
and Interventions, Society of Cardiovascular Computed lipoprotein responses and inhibitory effect on carotid
Tomography, and Society of Thoracic Surgeons. J Am atherosclerosis progression. J Cardiovasc Pharmacol. 1997
Coll Cardiol. 2017 May 2;69(17):2212-2241. doi: 10.1016/j. Dec;30(6):784-789. doi: 10.1097/00005344-199712000-00013.
jacc.2017.02.001. PMID: 28291663. PMID: 9436818.
Philippine Heart Association CAD Guidelines Writing Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and
Committee. 2014 PHA Clinical practice guidelines for the treatment of hypertriglyceridemia: an Endocrine Society
diagnosis and management of patients with coronary artery clinical practice guideline. J Clin Endocrinol Metab. 2012
disease. Philippine Heart Association. http://www.philheart. Sep;97(9):2969-2989. doi: 10.1210/jc.2011-3213. PMID:
org/. 27 Nov 2014. 22962670.
Scottish Intercollegiate Guidelines Network. Management of Bhatnagar D, Soran H, Durrington PN. Hypercholesterolaemia
stable angina. SIGN. http://www.sign.ac.uk. Feb 2007. and its management. BMJ. 2008 Aug 21;337:a993. doi:
She J, Lou B, Liu H, et al. ARNI versus ACEI/ARB in reducing 10.1136/bmj.a993. PMID: 18719012.
cardiovascular outcomes after myocardial infarction. ESC Braunwald E, Zipes DP, Libby P. Risk for atherosclerotic
Heart Fail. 2021 Dec;8(6):4607-4616. doi: 10.1002/ehf2.13644. disease. In: Heart Disease: A Textbook of Cardiovascular
Accessed 22 Feb 2022. PMID: 34664407. Medicine. 6th ed. Philadelphia: W.B. Saunders Company;
Task Force Members, Montalescot G, Sechtem U, Achenbach 2001:1010-1022.
REFERENCES
S, et al. 2013 ESC guidelines on the management of stable Bruckert E, Giral P, Tellier P. Perspectives in cholesterol-
coronary artery disease: the Task Force on the management l o w er i ng th erap y : the role of e ze t i m i b e , a ne w
of stable coronary artery disease of the European Society of selective inhibitor of intestinal cholesterol absorption.
Cardiology. Eur Heart J. 2013 Oct;34(38):2949-3003. doi: Circulation. 2003 Jul;107(25):3124-3128. doi: 10.1161/01.
10.1093/eurheartj/eht296. PMID: 23996286. CIR.0000072345.98581.24. PMID: 12835406.
Visseren FLJ, Mach F, Smulders YM, et al; ESC National Cacoub P, Tocque-Le Gousse E, Fabry C, et al. Application
Cardiac Societies, ESC Scientific Document Group. 2021 in general practice of treatment guidelines for patients
ESC guidelines on cardiovascular disease prevention in with dyslipidaemia: the RESPECT study. Arch Cardiovasc
clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. Dis. 2008 Nov-Dec;101(11-12):715-721. doi: 10.1016/j.
doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021. acvd.2008.09.011. PMID: 19059566.
PMID: 34458905.
Catapano AL, Graham I, De Backer G, et al; Authors/Task
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/ Force Members; Additional Contributor. 2016 ESC/EAS
AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/ guidelines for the management of dyslipidaemias. Eur Heart
PCNA guideline for the prevention, detection, evaluation, J. 2016 Oct;37(39):2999-3058. doi: 10.1093/eurheartj/ehw272.
and management of high blood pressure in adults: a report PMID: 27567407.
of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. J Am Cheung BM, Cheng CH, Lau CP, et al. 2016 Consensus
Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j. statement on prevention of atherosclerotic cardiovascular
jacc.2017.11.006. PMID: 29146535. disease in the Hong Kong population. Hong Kong Med J.
2017 Apr;23(2):191-201. doi: 10.12809/hkmj165045. PMID:
28387202.
Choice of lipid-regulating drugs. Med Lett Drugs Ther. 2001
Dyslipidemia May;43(1105):43-48. PMID: 11378632.
Academy of Medicine of Malaysia, Ministry of Health of Cybulska B, Szostak WB, Podolec P, et al. Polish forum for
Malaysia. Clinical practice guidelines on dyslipidaemia. 3rd prevention guidelines on dyslipidemia. Kardiol Pol. 2008
ed. Academy of Medicine of Malaysia. http://www.acadmed. Nov;66(11):1239-1242. PMID: 19105106.
org.my. Aug 2003. Dos Santos JE, Loures-Vale AA, Novazzi JP, et al. Evaluation of
Alshamiri M, Ghanaim MMA, Barter P, et al. Expert opinion efficacy and safety of etofibrate in primary hyperlipidemia.
on the applicability of dyslipidemia guidelines in Asia and A multicenter study [abstract]. Arq Bras Cardiol. 1996
the Middle East. Int J Gen Med. 2018 Jul 18;11:313-322. Dec;67(6):419-422. PMID: 9246832.
doi: 10.2147/IJGM.S160555. Accessed 30 Jan 2019. PMID: Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline
30050317. on lifestyle management to reduce cardiovascular risk: a
American Diabetes Association. Standards of medical care in report of the American College of Cardiology/American
diabetes - 2011. Diabetes Care. 2011 Jan;34(Suppl 1):S11-S61. Heart Association Task Force on Practice Guidelines.
doi: 10.2337/dc11-S011. PMID: 21193625. Circulation. 2014 Jun;129(25 Suppl 2). doi: 10.1161/01.
American Dietetic Association. Disorders of lipid metabolism. cir.0000437740.48606.d1. PMID: 24222015.
Evidence-based nutrition practice guideline (executive European Association for Cardiovascular Prevention and
summary). Academy of Nutrition and Dietetics. http://www. Rehabilitation, Reiner Z, Catapano AL, et al. ESC/EAS
andeal.org. 2011. guidelines for the management of dyslipidaemias: The
American Family Physician. U.S. Preventive Services Task Force Task Force for the Management of Dyslipidaemias for
screening for lipid disorders in adults: recommendation the European Association Cardiology (ESC) and the
statement. Am Fam Physician. 2009 Dec 1;80(11):1273-1274. European Atherosclerosis Society (EAS). Eur Heart J. 2011
https://www.aafp.org. Accessed 24 Apr 2018. Jul;32(14):1769-1818. doi: 10.1093/eurheartj/ehr158. PMID:
21712404.
Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian
Cardiovascular Society guidelines for the management of Expert Panel on Detection, Evaluation, and Treatment of High
dyslipidemia for the prevention of cardiovascular disease in Blood Cholesterol in Adults. Third Report of the National
the adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: Cholesterol Education Program (NCEP) Expert Panel
10.1016/j.cjca.2016.07.510. PMID: 27712954. detection, evaluation, and treatment of high blood cholesterol
in adults (Adult Treatment Panel III) final report. Circulation.
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA
2002 Dec 17;106(25):3143-3421. PMID: 12485966.
guideline on the primary prevention of cardiovascular disease:
a report of the American College of Cardiology/American Ferdowsian HR, Barnard ND. Effects of plant-based diets on
Heart Association Task Circulation. 2019;140(11):e596-e646. plasma lipids. Am J Cardiol. 2009 Oct;104(7):947-956. doi:
doi: 10.1161/CIR.0000000000000678. PMID: 30879355. 10.1016/j.amjcard.2009.05.032. PMID: 19766762.
275
Fletcher B, Berra K, Ades P, et al. Managing abnormal blood lipids: Endocrinologists’ guidelines for management of dyslipidemia
a collaborative approach. Circulation. 2005 Nov;112(20):3184- and prevention of atherosclerosis. Endocr Pract. 2012
3209. doi: 10.1161/CIRCULATIONAHA.105.169180. PMID: Mar-Apr;18(Suppl 1):1-78. doi: 10.4158/ep.18.s1.1. PMID:
16286609. 22522068.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/ Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC
AHA guideline on the assessment of cardiovascular risk: expert consensus decision pathway on the role of non-statin
a report of the American College of Cardiology/American therapies for LDL-cholesterol lowering in the management
Heart Association Task Force on Practice Guidelines. of atherosclerotic cardiovascular disease risk: a report of the
Circulation. 2014 Jun;129(Suppl 2):S49-S73. doi: 10.1161/01. American College of Cardiology Task Force on clinical expert
cir.0000437741.48606.98. PMID: 24222018. consensus documents. J Am Coll Cardiol. 2016 Jul;68(1):92-
Gonzalez-Santos LE, Oliva R, Jimeno C, et al. Executive 125. doi: 10.1016/j.jacc.2016.03.519. PMID: 27046161.
summary of the 2020 clinical practice guidelines for the Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines
management of dyslipidemia in the Philippines: 2020 for the management of dyslipidaemias: lipid modification to
Dyslipidemia CPG. Journal of the ASEAN Federation of reduce cardiovascular risk. ESC. http://www.escardio.org. 31
Endocrine Societies. 2021 Mar;36(1):7-13. https://www. Aug 2019. Accessed 09 Sep 2019.
asean-endocrinejournal.org. Accessed 22 Mar 2021. Ministry of Health Malaysia, Academy of Medicine Malaysia,
Grundy SM, Cleeman JL, et al. Implications of recent clinical National Heart Association of Malaysia. 5th edition of
trials for the National Cholesterol Education Program clinical practice guidelines on management of dyslipidaemia
REFERENCES
Adult Treatment Panel III guidelines. Circulation. 2004 2017. Academy of Medicine Malaysia. http://www.acadmed.
Jul;110(2):227-239. doi: 10.1161/01.CIR.0000133317.49796.0E. org.my. 2017.
PMID: 15249516. Ministr y of Health Malaysia , Malaysian Society of
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/ Ophthalmology and Academy of Medicine Malaysia. Clinical
AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/ practice guidelines on screening of diabetic retinopathy.
NLA/PCNA guideline on the management of blood Academy of Medicine of Malaysia. http://www.acadmed.
cholesterol: executive summary: a report of the American org.my. Jun 2011.
College of Cardiology/American Heart Association Task Ministry of Health Singapore. Clinical practice guidelines: lipids.
Force on Clinical Practice Guidelines. J Am Coll Cardiol. MOH (Singapore). http://www.moh.gov.sg. 2006.
2019 Jun 25;73(24):3168-3209. doi: 10.1016/j.jacc.2018.11.002. Ministry of Health Singapore. MOH clinical practice guidelines
Accessed 29 Jan 2019. PMID: 30423391. on lipids. Ministry of Health Singapore. https://www.moh.
Guerrero AE, Gonzalez-Santos LE, Caole-Ang IV, et al. 2015 gov.sg. Dec 2016.
Updated clinical practice guidelines for the management National Heart Association of Malaysia, Ministry of Health and
of dyslipidemia in the Philippines. Philippine Society of the Academy of Medicine Expert Panel. CPG in management
Endocrinology, Diabetes and Metabolism. http://endo- of dyslipidaemia. National Heart Association of Malaysia.
society.org.ph. 2015. http://www.malaysianheart.org. 2011.
Gupta EK, Ito MK. Ezetimibe: the first in a novel class of National Institute for Health and Care Excellence. Lipid
selective cholesterol-absorption inhibitors. Heart Dis. 2002 modification: cardiovascular risk assessment and the
Nov-Dec;4(6):399-409. doi: 10.1097/00132580-200211000- modification of blood lipids for the primary and secondary
00011. PMID: 12441019. prevention of cardiovascular disease. NICE clinical guideline
Handelsman Y, Jellinger PS, Guerin CK, et al. Consensus 67. NICE. http://www.nice.org.uk. May 2008.
statement by the American Association of Clinical Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial
Endocrinologists and American College of Endocrinology hypercholesterolemia is underdiagnosed and undertreated
on the management of dyslipidemia and prevention of in the general population: guidance for clinicians to prevent
cardiovascular disease algorithm – 2020 executive summary. coronary heart disease: consensus statement of the European
Endocr Pract. 2020 Oct;26(10):1196-1224. doi: 10.4158/CS- Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-
2020-0490. Accessed 25 Jan 2021. PMID: 33471721. 3490a. doi: 10.1093/eurheartj/eht273. Accessed 17 Apr 2020.
Institute for Clinical Systems Improvement (ICSI). ICSI health PMID: 23956253.
care guideline: lipid management in adults. 10th ed. ICSI. Pereira de Moura JMDS, Pacheco Mendes PFAP, Reigota CP, et
http://www.icsi.org. 2007. al. New drugs coming up in the field of lipid control. European
International Diabetes Federation. The IDF consensus Society of Cardiology (ESC). https://www.escardio.org. 16
worldwide definition of the metabolic syndrome. International Dec 2020. Accessed 02 Mar 2021.
Diabetes Federation. http://www.idf.org. Apr 2005. Philippine Heart Association. The clinical practice guidelines
Iqbal Z, Ho JH, Adam S, et al. Managing hyperlipidaemia for the management of dyslipidemia in the Philippines
in patients with COVID-19 and during its pandemic: [executive summary]. Philippine Heart Association. http://
an expert panel position statement from HEART UK. www.philheart.org. Dec 2005.
Atherosclerosis. 2020 Nov;313:126–136. doi: 10.1016/j. Reiner Z. Combined therapy in the treatment of dyslipidemia.
atherosclerosis.2020.09.008. Accessed 22 Feb 2021. PMID: Fundam Clin Pharmacol. 2010 Feb;24(1):19-28. doi:
33045618. 10.1111/j.1472-8206.2009.00764.x. PMID: 19682080.
Jellinger PS, Dickey RA, Ganda OP, et al; AACE Lipid Rosenson RS, Durrington P. Familial hypercholesterolemia in
Guidelines Committee. The American Association of Clinical adults: overview. UpToDate. https://www.uptodate.com. Apr
Endocrinologists. AACE medical guidelines for clinical 2019. Accessed 17 Apr 2020.
practice for the diagnosis and treatment of dyslipidemia
and prevention of atherogenesis. Endocr Pract. 2000 Rosenson RS, Durrington P. Familial hypercholesterolemia in
Mar;6(2):162-213. PMID: 11428356. adults: treatment. UpToDate. https://www.uptodate.com. Nov
2019. Accessed 20 Apr 2020.
Jellinger PS, Handelsman Y, Rosenblit PD, et al. American
Association of Clinical Endocrinologists and American Rosenson RS. Lipoprotein classification, metabolism, and
College of Endocrinology guidelines for management of role in atherosclerosis. UpToDate. https://www.uptodate.
dyslipidemia and prevention of cardiovascular disease. Endocr com. Jun 2015.
Pract. 2017 Apr;23(Suppl 2):1-87. doi: 10.4158/EP171764. Rosenson RS. Low density lipoprotein cholesterol lowering with
APPGL. PMID: 28437620. drugs other than statins and PCSK9 inhibitors. UpToDate.
Jellinger PS, Smith DA, Mehta AE, et al; AACE Task https://www.uptodate.com. 04 Jan 2021. Accessed 28 Jan 2021.
Force for Management of Dyslipidemia and Prevention Safi SZ, Qvist R, Kumar S, et al. Molecular mechanisms of
of Atherosclerosis. American Association of Clinical diabetic retinopathy, general preventive strategies, and novel
276
therapeutic targets. Biomed Res Int. 2014;2014:801269. doi: Heart Failure - Acute
10.1155/2014/801269. PMID: 25105142.
Academy of Medicine Malaysia, Ministry of Health Malaysia,
Semenkovich CF, Goldberg AC, Goldberg IJ. Disorders of lipid National Heart Association of Malaysia. Clinical practice
metabolism. In: Melmed S, Polonsky KS, Larsen PR, et al. guidelines management of heart failure 2019. 4th ed. National
Williams Textbook of Endocrinology. 13th ed. Philadelphia, Heart Association of Malaysia. https://www.malaysianheart.
PA: Elsevier Inc; 2016:1660-1700. org. 04 Sep 2019. Accessed 10 Sep 2019.
Siscovick DS, Barringer TA, Fretts AM, et al; American Heart Authors/task force members; document reviewers. 2016 ESC
Association Nutrition Committee of the Council on Lifestyle guidelines for the diagnosis and treatment of acute and
and Cardiometabolic Health; Council on Epidemiology chronic heart failure: The task force for the diagnosis and
and Prevention; Council on Cardiovascular Disease in the treatment of acute and chronic heart failure of the European
Young; Council on Cardiovascular and Stroke Nursing; and Society of Cardiology (ESC). Developed with the special
Council on Clinical Cardiology. Omega-3 polyunsaturated contribution of the Heart Failure Association (HFA) of the
fatty acid (Fish Oil) supplementation and the prevention ESC. Eur J Heart Fail. 2016 May 20:1-85. doi: 10.1002/ejhf.592.
of clinical cardiovascular disease: a science advisory from PMID: 27207191.
the American Heart Association. Circulation. 2017 Apr
Biesbroek PS, Hirsch A, Zweerink A, et al. Additional diagnostic
11;135(15):e867-e884. doi: 10.1161/CIR.0000000000000482. value of CMR to the European Society of Cardiology (ESC)
PMID: 28289069. position statement criteria in a large clinical population of
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/ patients with suspected myocarditis. Eur Heart J Cardiovasc
REFERENCES
AHA guideline on the treatment of blood cholesterol to Imaging. 2018 Dec 1;19(12):1397-1407. doi: 10.1093/ehjci/
reduce atherosclerotic cardiovascular risk in adults: a jex308. Accessed 16 Mar 2022. PMID: 29186442.
report of the American College of Cardiology/American Bozkurt B, Hershberger RE, Butler J, et al. 2021 ACC/AHA key
Heart Association Task Force on Practice Guidelines. data elements and definitions for heart failure: a report of the
Circulation. 2013 Nov;129(25 Suppl 2):S1-S45. doi: American College of Cardiology/American Heart Association
10.1161/01.cir.0000437738.63853.7a. PMID: 24222016. Task Force on Clinical Data Standards (Writing Committee
The Management of Dyslipidemia for Cardiovascular Risk to Develop Clinical Data Standards for Heart Failure). J Am
Reduction Work Group. VA/DoD clinical practice guideline Coll Cardiol. 2021 Apr 27;77(16):2053-2150. doi: 10.1016/j.
for the management of dyslipidemia for cardiovascular risk jacc.2020.11.012. Accessed 02 Jul 2021. PMID: 33250265.
reduction. U.S. Department of Veterans Affairs. https://www. Dickstein K, Cohen-Solal A, Filippatos G, et al; ESC Committee
healthquality.va.gov. Jun 2020. Accessed 25 Jan 2021. for Practice Guidelines (CPG). ESC Guidelines for the
The Task Force on Diabetes and Cardiovascular Diseases of the diagnosis and treatment of acute and chronic heart failure
European Society of Cardiology (ESC) and of the European 2008: the Task Force for the Diagnosis and Treatment of
Association for the Study of Diabetes (EASD). Guidelines on Acute and Chronic Heart Failure 2008 of the European Society
diabetes, pre-diabetes, and cardiovascular diseases: executive of Cardiology. Developed in collaboration with the Heart
summary. Euro Heart J. 2007 Jan;28(1):88-136. http://www. Failure Association of the ESC (HFA) and endorsed by the
escardio.org. PMID: 17220161. European Society of Intensive Care Medicine (ESICM). Eur
U.S. Food & Drug Administration (US FDA). FDA approves Heart J. 2008 Oct;29(19):2388-2442. doi: 10.1093/eurheartj/
add-on therapy for patients with genetic form of severely ehn309. PMID: 18799522.
high cholesterol. US FDA. https://www.fda.gov. 11 Feb 2021. Heart Failure Society of America, Lindelfeld J, Albert NM, et al.
Accessed 02 Mar 2021. Executive summary: HFSA 2010 comprehensive heart failure
Vijan S. Screening for lipid disorders in adults. UpToDate. practice guideline. J Card Fail. 2010 Jun;16(6):e1-194. doi:
https://www.uptodate.com. Dec 2016. 10.1016/j.cardfail.2010.04.004. PMID: 20610207.
Virani SS, Morris PB, Agarwala A, et al. 2021 ACC expert Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/
consensus decision pathway on the management of ASCVD ACC/HFSA guideline for the management of heart failure:
risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology/American
a report of the American College of Cardiology Solution Heart Association Joint Committee on Clinical Practice
Set Oversight Committee. J Am Coll Cardiol. 2021 Aug Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.
31;78(9):960-993. doi: 10.1016/j.jacc.2021.06.011. Accessed doi: 10.1161/CIR.0000000000001063. Accessed 24 May 2022.
24 Jan 2022. PMID: 34332805. PMID: 35363499.
Visseren FLJ, Mach F, Smulders YM, et al; ESC National Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the
Cardiac Societies, ESC Scientific Document Group. 2021 diagnosis and management of chronic coronary syndromes:
ESC guidelines on cardiovascular disease prevention in The Task Force for the diagnosis and management of chronic
clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. coronary syndromes of the European Society of Cardiology
doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021. (ESC). Eur Heart J. 2019:1-71. doi: 10.1093/eurheartj/ehz425.
Accessed 10 Sep 2019. PMID: 31504439.
PMID: 34458905.
Kuin BKW, Yee OH, Ping CLS, et al. 2020 Clinical practice
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/
guidelines on the diagnosis and management of heart failure
AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/
- a comprehensive updated guideline from the Heart Failure
PCNA guideline for the prevention, detection, evaluation,
Society (Singapore). Heart Failure Society (Singapore). https://
and management of high blood pressure in adults: a report
www.hfss.org.sg. 2020. Accessed 27 Jan 2021.
of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. J Am McDonagh TA, Metra M, Adamo M, et al; ESC Scientific
Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j. Document Group. 2021 ESC guidelines for the diagnosis and
jacc.2017.11.006. PMID: 29146535. treatment of acute and chronic heart failure. Eur Heart J. 2021
Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368.
Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2016 Accessed 15 Dec 2021. PMID: 34447992.
ACC expert consensus decision pathway on the role of
non-statin therapies for LDL-cholesterol lowering in the McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee
management of atherosclerotic cardiovascular disease risk: a for Practice Guidelines. ESC Guidelines for the diagnosis and
report of the American College of Cardiology Task Force on treatment of acute and chronic heart failure 2012: The Task
Force for the Diagnosis and Treatment of Acute and Chronic
Clinical Expert Consensus Documents. J Am Coll Cardiol.
Heart Failure 2012 of the European Society of Cardiology.
2016 Jul 5;68(1):92-125. doi: 10.1016/j.jacc.2016.03.519.
Developed in collaboration with the Heart Failure Association
PMID: 27046161.
(HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-1847. doi:
10.1093/eurheartj/ehs104. PMID: 22611136.
277
Mebazaa A, Yilmaz MB, Levy P, et al. Recommendations on pre- Heart J. 2017 Sep;38(36):2739-2791. doi: 10.1093/eurheartj/
hospital and early hospital management of acute heart failure: ehx391. Accessed 17 Sep 2020. PMID: 28886619.
a consensus paper from the Heart Failure Association of the Bozkurt B, Hershberger RE, Butler J, et al. 2021 ACC/AHA key
European Society of Cardiology, the European Society of data elements and definitions for heart failure: a report of the
Emergency Medicine and the Society of Academic Emergency American College of Cardiology/American Heart Association
Medicine--short version. Eur Heart J. 2015 Aug 7;36(30):1958- Task Force on Clinical Data Standards (Writing Committee
1966. doi: 10.1093/eurheartj/ehv066. PMID: 25998514. to Develop Clinical Data Standards for Heart Failure). J Am
Ministry of Health Malaysia, Academy of Medicine Malaysia, Coll Cardiol. 2021 Apr 27;77(16):2053-2150. doi: 10.1016/j.
National Heart Association of Malaysia. Management of heart jacc.2020.11.012. Accessed 02 Jul 2021. PMID: 33250265.
failure, 3rd edition clinical practice guideline 2014. Ministry Dickstein K, Cohen-Solal A, Filippatos G, et al; ESC Committee
of Health Malaysia. http://www.moh.gov.my. 2014. for Practice Guidelines (CPG). ESC Guidelines for the
National Clinical Guideline Centre. Acute heart failure: diagnosis and treatment of acute and chronic heart failure
diagnosing and managing acute heart failure in adults. 2008: the Task Force for the Diagnosis and Treatment of
Clinical guideline 187. National Institute for Health and Acute and Chronic Heart Failure 2008 of the European Society
Care Excellence (NICE). http://www.nice.org.uk. Oct 2014. of Cardiology. Developed in collaboration with the Heart
Failure Association of the ESC (HFA) and endorsed by the
NHFA CSANZ Heart Failure Working Group, Atherton JJ, European Society of Intensive Care Medicine (ESICM). Eur
Sindone A, Pasquale CG, et al. National Heart Foundation of Heart J. 2008 Oct;29(19):2388-2442. doi: 10.1093/eurheartj/
Australia and Cardiac Society of Australia and New Zealand: ehn309. PMID: 18799522.
REFERENCES
guidelines for the prevention, detection, and management DiNicolantonio JJ, Bhutani J, McCarty MF, et al. Coenzyme Q10
of heart failure in Australia 2018. Heart, Lung Circ. 2018 for the treatment of heart failure: a review of the literature.
Oct;27(10):1123-1208. doi: 10.1016/j.hlc.2018.06.1042. Open Heart. 2015 Oct 19;2(1):e000326. doi: 10.1136/
Accessed 21 Mar 2019. PMID: 30077227. openhrt-2015-000326. PMID: 26512330.
Nunez J, Minana G, Santas E, et al. Cardiorenal syndrome Heart Failure Society of America, Lindelfeld J, Albert NM, et al.
in acute heart failure: revisiting paradigms. Rev Esp Executive summary: HFSA 2010 comprehensive heart failure
Cardiol (Engl Ed). 2015 May;68(5):426-435. doi: 10.1016/j. practice guideline. J Card Fail. 2010 Jun;16(6):e1-194. doi:
rec.2014.10.016. Accessed 16 Mar 2022. PMID: 25758162. 10.1016/j.cardfail.2010.04.004. PMID: 20610207.
NWT clinical practice guidelines for primary community care Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/
nursing - cardiovascular system. Congestive heart failure. ACC/HFSA guideline for the management of heart failure:
HSS Professionals. https://www.hss.gov.nt.ca. Sep 2004. a report of the American College of Cardiology/American
Accessed 16 Mar 2022. Heart Association Joint Committee on Clinical Practice
The European Society for Cardiology (ESC). ESC guidance Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.
for the diagnosis and management of CV disease during the doi: 10.1161/CIR.0000000000001063. Accessed 24 May 2022.
COVID-19 pandemic. ESC. https://www.escardio.org. 10 June PMID: 35363499.
2020. Accessed 22 Feb 2021. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005
The Task Force for the Diagnosis and Treatment of CHF of guideline update for the diagnosis and management of
the European Society of Cardiology. ESC Guidelines for the chronic heart failure in the adult: a report of the American
diagnosis and treatment of acute and chronic heart failure: College of Cardiology/American Heart Association Task
full text (update 2005). Eur Heart J. 2005:001-36. Force on Practice Guidelines (Writing Committee to update
the 2001 guidelines for the evaluation and management of
The Task Force for the management of COVID-19 of the heart failure): developed in collaboration with the American
European Society of Cardiology. ESC guidance for the College of Chest Physicians and the International Society
diagnosis and management of cardiovascular disease during for Heart and Lung Transplantation: endorsed by the Heart
the COVID-19 pandemic: part 2-care pathways, treatment, Rhythm Society. Circulation. 2005 Sep;112(12):e154-e235.
and follow-up. Eur Heart J. 2022 Mar 14;43(11):1059-1103. http://circ.ahajournals.org. PMID: 16160202.
doi: 10.1093/eurheartj/ehab697. Accessed 28 May 2022.
Jessup M, Abraham WT, Casey DE, et al. 2009 focused update:
PMID: 34791154.
ACCF/AHA guidelines for the diagnosis and management of
Thibodeau JT, Turer AT, Gualano SK, et al. Characterization heart failure in adults: a report of the American College of
of a novel symptom of advanced heart failure: bendopnea. Cardiology Foundation/American Heart Association Task
JACC Heart Fail. 2014 Feb;2(1):24-31. doi: 10.1016/j. Force on Practice Guidelines: developed in collaboration with
jchf.2013.07.009. PMID: 24622115. the International Society for Heart and Lung Transplantation.
Tsutsui H, Isobe J, Ito H, et al. JCS 2017/JHFS 2017 guideline Circulation. 2009 Apr;119(14):1977-2016. doi: 10.1161/
on diagnosis and treatment of acute and chronic heart failure CIRCULATIONAHA.109.192064. PMID: 19324967.
- digest version. Circ J. 2019 Sep 25;83(10):2084-2184. doi: Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the
10.1253/circj.CJ-19-0342. Accessed 03 May 2021. PMID: diagnosis and management of chronic coronary syndromes:
31511439. The Task Force for the diagnosis and management of chronic
coronary syndromes of the European Society of Cardiology
(ESC). Eur Heart J. 2019:1-71. doi: 10.1093/eurheartj/ehz425.
Heart Failure - Chronic Accessed 10 Sep 2019. PMID: 31504439.
Abarquez RF Jr, Reganit PF, Chungunco CN, et al. Chronic heart Kuin BKW, Yee OH, Ping CLS, et al. 2020 Clinical practice
failure clinical practice guidelines’ class 1-A pharmacologic guidelines on the diagnosis and management of heart failure
recommendations: start-to-end synergistic drug therapy? - a comprehensive updated guideline from the Heart Failure
ASEAN Heart J. 2016 Mar 8;24:4. doi: 10.7603/s40602-016- Society (Singapore). Heart Failure Society (Singapore). https://
0004-5. PMID: 27054142. www.hfss.org.sg. 2020. Accessed 27 Jan 2021.
Academy of Medicine Malaysia, Ministry of Health Malaysia, Littarru GP. Ubiquinol, new insights into the most active form
National Heart Association of Malaysia. Clinical practice of Coenzyme Q10. France: Medicatrix; 2014:73, 108.
guidelines management of heart failure 2019. 4th ed. National McDonagh TA, Metra M, Adamo M, et al; ESC Scientific
Heart Association of Malaysia. https://www.malaysianheart. Document Group. 2021 ESC guidelines for the diagnosis and
org. 04 Sep 2019. Accessed 10 Sep 2019. treatment of acute and chronic heart failure. Eur Heart J. 2021
American Diabetes Association. Standards of medical care in Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368.
diabetes - 2020. Diabetes Care. 2020 Jan;43(Suppl 1):S1-S212. Accessed 15 Dec 2021. PMID: 34447992.
https://care.diabetesjournals.org. Accessed 06 Jan 2020. McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee
Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS for Practice Guidelines. ESC Guidelines for the diagnosis and
guidelines for the management of valvular heart disease. Eur treatment of acute and chronic heart failure 2012: The Task
Force for the Diagnosis and Treatment of Acute and Chronic
278
Heart Failure 2012 of the European Society of Cardiology. Visseren FLJ, Mach F, Smulders YM, et al; ESC National
Developed in collaboration with the Heart Failure Association Cardiac Societies, ESC Scientific Document Group. 2021
(HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-1847. doi: ESC guidelines on cardiovascular disease prevention in
10.1093/eurheartj/ehs104. PMID: 22611136. clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337.
Ministry of Health Malaysia, Academy of Medicine Malaysia, doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021.
National Heart Association of Malaysia. Management of heart PMID: 34458905.
failure, 3rd edition clinical practice guideline 2014. Ministry Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/
of Health Malaysia. http://www.moh.gov.my. 2014. AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/
National Heart Foundation of Australia and the Cardiac Society PCNA guideline for the prevention, detection, evaluation,
of Australia and New Zealand (Chronic Heart Failure Expert and management of high blood pressure in adults: a report
Writing Panel). Guidelines for the prevention, detection and of the American College of Cardiology/American Heart
management of chronic heart failure in Australia. http://www. Association Task Force on Clinical Practice Guidelines. J Am
heartfoundation.org.au. Oct 2011. Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j.
National Institute for Health and Care Excellence (NICE). jacc.2017.11.006. PMID: 29146535.
Chronic heart failure in adults: diagnosis and management. WHO Expert Consultation. Appropriate body-mass index
NICE. http://www.nice.org.uk. Sep 2018. Accessed 21 Mar for Asian populations and its implications for policy and
2019. intervention strategies. Lancet. 2004 Jan 10;363(9403):157-
NHFA CSANZ Heart Failure Working Group, Atherton JJ, 163. doi: 10.1016/S0140-6736(03)15268-3. PMID: 14726171.
Writing Committee; Maddox TM, Januzzi Jr JL, Allen LA,
REFERENCES
Sindone A, Pasquale CG, et al. National Heart Foundation of
Australia and Cardiac Society of Australia and New Zealand: et al. 2021 Update to the 2017 ACC expert consensus
guidelines for the prevention, detection, and management decision pathway for optimization of heart failure treatment:
of heart failure in Australia 2018. Heart, Lung Circ. 2018 answers to 10 pivotal issues about heart failure with reduced
Oct;27(10):1123-1208. doi: 10.1016/j.hlc.2018.06.1042. ejection fraction: a report of the American College of
Accessed 21 Mar 2019. PMID: 30077227. Cardiology Solution Set Oversight Committee. J Am Coll
NHS. Alcohol units. NHS. https://www.nhs.uk. 13 Apr 2018. Cardiol. 2021 Jan 04;S0735-1097(20)37867-0. doi: 10.1016/j.
jacc.2020.11.022. Accessed 15 Jan 2021. PMID: 33446410.
Accessed 05 Jul 2021.
Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA
Onur S, Niklowitz P, Jacobs G, et al. Association between serum focused update on new pharmacological therapy for heart
level of ubiquinol and NT-proBNP, a marker for chronic heart failure: an update of the 2013 ACCF/AHA guideline for the
failure, in healthy elderly subjects (abstract). Biofactors. 2015 management of heart failure: a report of the American College
Jan-Feb;41(1):35-43. doi: 10.1002/biof.1198. PMID: 25728634. of Cardiology/American Heart Association Task Force on
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia Clinical Practice Guidelines and the Heart Failure Society of
(PERKI). Pedoman Tatalaksana Gagal Jantung. Edisi Pertama. America. J Am Coll Cardiol. 2016 Sep 27;68(13):1476-1488.
Jakarta; 2015. doi: 10.1016/j.jacc.2016.05.011. PMID: 27216111.
Pirracchio R, Cholley B, De Hert S, et al. Diastolic heart
failure in anaesthesia and critical care. Br J Anaesth. 2007
Jun;98(6):707-721. doi: 10.1093/bja/aem098. Accessed 04 Jul
2018. PMID: 17468492. Hypertension
Ponikowski P, Voors AA, Anker SD, et al; authors/task force Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert
members; document reviewers. 2016 ESC guidelines for the consensus document on hypertension in the elderly: a report
diagnosis and treatment of acute and chronic heart failure: of the American College of Cardiology Foundation Task
The Task Force for the diagnosis and treatment of acute and Force on Clinical Expert Consensus documents developed
chronic heart failure of the European Society of Cardiology in collaboration with the American Academy of Neurology,
(ESC). Developed with the special contribution of the Heart American Geriatrics Society, American Society for Preventive
Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Cardiology, American Society of Hypertension, American
May 20:1-85. doi: 10.1002/ejhf.592. PMID: 27207191. Society of Nephrology, Association of Black Cardiologists,
Seferovic PM, Ponikowski P, Anker SD, et al. Clinical practice and European Society of Hypertension. J Am Coll Cardiol.
update on heart failure 2019: pharmacotherapy, procedures, 2011 May;57(20):2037-2114. doi: 10.1016/j.jacc.2011.01.008.
devices and patient management. An expert consensus PMID: 21524875.
meeting report of the Heart Failure Association of the Bakris G, Ali W, Parati G. ACC/AHA versus ESC/ESH on
European Society of Cardiology. Eur J Heart Fail. 2019 hypertension guidelines: JACC guideline comparison. J Am
Oct;21(10):1169-1186. doi: 10.1002/ejhf.1531. Accessed 02 Coll Cardiol. 2019 Jun 18;73(23):3018-3026. doi: 10.1016/j.
Oct 2019. PMID: 31129923. jacc.2019.03.507. Accessed 29 Aug 2019. PMID: 31196460.
The European Society for Cardiology (ESC). ESC guidance Bennett PC, Silverman S, Gill P. Hypertension and peripheral
for the diagnosis and management of CV disease during the
arterial disease. J Hum Hypertens. 2009 Mar;23(3):213-215.
COVID-19 pandemic. ESC. https://www.escardio.org. 10 June
doi: 10.1038/jhh.2008.126. PMID: 18923435.
2020. Accessed 22 Feb 2021.
The Task Force for the management of COVID-19 of the Cheung BM, Cheng CH, Lau CP, et al. 2016 Consensus
European Society of Cardiology. ESC guidance for the statement on prevention of atherosclerotic cardiovascular
diagnosis and management of cardiovascular disease during disease in the Hong Kong population. Hong Kong Med J.
the COVID-19 pandemic: part 2-care pathways, treatment, 2017 Apr;23(2):191-201. doi: 10.12809/hkmj165045. PMID:
and follow-up. Eur Heart J. 2022 Mar 14;43(11):1059-1103. 28387202.
doi: 10.1093/eurheartj/ehab697. Accessed 28 May 2022. Chobanian AV, Bakris GL, Black HR, et al; National Heart,
PMID: 34791154. Lung, and Blood Institute Joint National Committee on
Tsutsui H, Isobe J, Ito H, et al. JCS 2017/JHFS 2017 guideline Prevention, Detection, Evaluation, and Treatment of High
on diagnosis and treatment of acute and chronic heart failure Blood Pressure; National High Blood Pressure Education
- digest version. Circ J. 2019 Sep 25;83(10):2084-2184. doi: Program Coordinating Committee. The seventh report of
10.1253/circj.CJ-19-0342. Accessed 03 May 2021. PMID: the Joint National Committee on prevention, detection,
31511439. evaluation, and treatment of high blood pressure: the JNC 7
van der Meer P, Gaggin HK, Dec GW. ACC/AHA versus ESC report. JAMA. 2003 May;289(19):2560-2572. doi: 10.1001/
guidelines on heart failure: JACC guideline comparison. J Am jama.289.19.2560. PMID: 12748199.
Coll Cardiol. 2019 Jun 04;73(21):2756-2768. doi: 10.1016/j. Clerkin KJ, Fried JA, Raikhelkar J, et al. COVID-19 and
jacc.2019.03.478. Accessed 02 Oct 2019. PMID: 31146820. cardiovascular disease. Circulation. 2020 May 19;141(20):1648-
1655. doi: 10.1161/CIRCULATIONAHA.120.046941.
Accessed 22 Feb 2021. PMID: 32200663.
279
Daud AM. Why is it important to measure blood pressure at National Clinical Guideline Centre and British Hypertension
home rather than just at the clinic? Asia-Pacific Cardiology. Society. Hypertension: clinical management of primary
2011;3(1):41-44. http://www.radcliffecardiology.com. hypertension in adults. London: National Institute for Health
Espallardo NL, Abrogena LAB, Mejia-Samonte M, et al. Clinical and Clinical Excellence. http://www.nice.org.uk/. Aug 2011.
pathways for the management of hypertension in family and National Heart Foundation of Australia. Guideline for the
community practice. The Filipino Family Physician. 2017 diagnosis and management of hypertension in adults - 2016.
Jul-Sep;55(3):143-161. Accessed 26 Mar 2018. National Heart Foundation of Australia. https://www.
European Society of Hypertension-European Society heartfoundation.org.au. 2016.
of Cardiology Guidelines Committee. 2003 European National Institute for Health and Care Excellence (NICE).
Society of Hypertension-European Society of Cardiology Hypertension in adults: diagnosis and management. NICE.
guidelines for the management of arterial hypertension. https://www.nice.org.uk. 28 Aug 2019. Accessed 24 Jun 2020.
J Hypertens. 2003 Jun;21(6):1011-1053. doi: 10.1097/01. Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension
hjh.0000059051.65882.32. PMID: 12777938. Canada’s 2018 guidelines for diagnosis, risk assessment,
Go AS, Bauman MA, Coleman King SM, et al. An effective prevention, and treatment of hypertension in adults and
approach to high blood pressure control: a science advisory children. Can J Cardiol. 2018 May;34(5):506-525. doi:
from the American Heart Association, the American College 10.1016/j.cjca.2018.02.022. Accessed 24 Jun 2020. PMID:
of Cardiology, and the Centers for Disease Control and 29731013.
Prevention. Hypertension. 2014 Apr;63(4):878-885. doi: O’Brien E, Coats A, Owens P, et al. Use and interpretation of
REFERENCES
10.1161/HYP.0000000000000003. PMID: 24243703. ambulatory blood pressure monitoring: recommendations

Institute for Clinical Systems Improvement (ICSI). Hypertension of the B r itish Hy p er tension S o cie ty. BMJ. 2000
diagnosis and treatment. ICSI. http://www.icsi.org. Nov 2010. Apr;320(7242):1128-1134. PMID: 10775227.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based Ona DID, Jimeno CA, Jasul GV, et al. Executive summary of
guideline for the management of high blood pressure in adults: the 2020 clinical practice guidelines for the management
report from the panel members appointed to the Eighth Joint of hypertension in the Philippines. J Clin Hypertens
National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507- (Greenwich). 2021 Aug 3:1-14. doi: 10.1111/jch.14335.
520. doi: 10.1001/jama.2013.284427. PMID: 24352797. Accessed 05 Aug 2021. PMID: 34343391.
Kaplan NM. Ambulatory and home blood pressure monitoring Parati G, Stergiou GS, Asmar R, et al; ESH Working Group
and white coat hypertension in adults. UpToDate. https:// on Blood Pressure Monitoring. European Society of
www.uptodate.com. Mar 2017. Hypertension practice guidelines for home blood pressure
Kario K, Chen CH, Park S, et al. Consensus document monitoring. J Hum Hypertens. 2010 Dec;24(12):779-785. doi:
on improving hypertension management in Asian 10.1038/jhh.2010.54. PMID: 20520631.
patients, taking into account Asian characteristics. Parving HH, Persson F, Lewis JB, et al. Aliskiren combined with
Hypertension. 2018 Mar;71(3):375-382. doi: 10.1161/ losartan in type 2 diabetes and nephropathy. N Engl J Med.
HYPERTENSIONAHA.117.10238. Accessed 28 Aug 2019. 2008 Jun;358(23):2433-2446. doi: 10.1056/NEJMoa0708379.
PMID: 29311253. PMID: 18525041.
Leung AA, Daskalopoulou SS, Dasgupta K, et al. Hypertension Pepine CJ, Handberg EM, Cooper-Dehoff RM, et al. A calcium
Canada’s 2017 guidelines for diagnosis, risk assessment, antagonist vs a non-calcium antagonist hypertension
prevention, and treatment of hypertension in adults. treatment strategy for patients with coronary artery disease:
Can J Cardiol. 2017 May;33(5):557-576. doi: 10.1016/j. The International Verapamil-Trandolapril Study (INVEST): a
cjca.2017.03.005. PMID: 28449828. randomized controlled trial. JAMA. 2003 Dec;290(21):2805-
Malaysian Society of Hypertension, Ministry of Health 2816. PMID: 14657064.
Malaysia, Academy of Medicine Malaysia. Management of Perhimpunan Dokter Spesialis Kardiovaskular Indonesia
hypertension. 4th ed. Academy of Medicine Malaysia. http:// (PERKI). Pedoman Tatalaksana Hipertensi Pada Penyakit
www.acadmed.org.my. 2013. Kardiovaskular. Edisi Pertama. Jakarta; 2015.
Malaysian Society of Hypertension, Ministry of Health Pickering TG, Hall JE, Appel LJ, et al. Recommendations for
Malaysia, Academy of Medicine of Malaysia. Clinical practice blood pressure measurement in humans and experimental
guidelines. Management of hypertension. 5th edition (2018). animals: part 1: blood pressure measurement in humans:
Academy of Medicine of Malaysia. http://www.acadmed.org. a statement for professionals from the Subcommittee of
my. 2018. Accessed 07 Dec 2018. Professional and Public Education of the American Heart
Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines Association Council on High Blood Pressure Research.
for the management of arterial hypertension: The Task Force Hypertension. 2005 Jan;45(1):142-161. doi: 10.1161/01.
for the Management of Arterial Hypertension of the European HYP.0000150859.47929.8e. PMID: 15611362.
Society of Hypertension (ESH) and of the European Society Qaseem A, Wilt TJ, Rich R, et al; Clinical Guidelines Committee
of Cardiology (ESC). Eur Heart J. 2007 Jun;28(12):1462-1536. of the American College of Physicians and the Commission on
doi: 10.1093/eurheartj/ehm236. PMID: 17562668. Health of the Public and Science of the American Academy of
Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal Family Physicians. Pharmacologic treatment of hypertension
of European guidelines on hypertension management: a in adults aged 60 years or older to higher versus lower
European Society of Hypertension Task Force document. blood pressure targets: a clinical practice guideline from the
J Hypertens. 2009 Nov;27(11):2121-2158. doi: 10.1097/ American College of Physicians and the American Academy
HJH.0b013e328333146d. PMID: 19838131. of Family Physicians. Ann Intern Med. 2017 Mar;166(6):430-
Ministry of Health Malaysia, Academy of Medicine of Malaysia 437. doi: 10.7326/M16-1785. PMID: 28135725.
& Malaysian Society of Hypertension. Clinical practice Task Force for the management of arterial hypertension of
guidelines: management of hypertension 3rd ed. Ministry of the European Society of Hypertension; Task Force for the
Health Malaysia. http://www.moh.gov.my. Feb 2008. management of arterial hypertension of the European Society
Ministry of Health Singapore. Clinical practice guidelines: of Cardiology. 2013 ESH/ESC guidelines for the management
hypertension. MOH (Singapore). http://www.moh.gov.sg. of arterial hypertension. Blood Press. 2013 Aug;22(4):193-
Jun 2005. 278. doi: 10.3109/08037051.2013.812549. PMID: 23777479.
Morin DP, Oikarinen L, Viitasalo M, et al. QRS duration predicts Task Force for the management of COVID-19 of the European
sudden cardiac death in hypertensive patients undergoing Society of Cardiology. ESC guidance for the diagnosis and
intensive medical therapy: the LIFE study. Eur Heart J. management of cardiovascular disease during the COVID-19
2009 Dec;30(23):2908-2914. doi: 10.1093/eurheartj/ehp321. pandemic: part 2-care pathways, treatment, and follow-up.
PMID: 19687165.
280
Eur Heart J. 2021 Nov 16;ehab697. doi: 10.1093/eurheartj/ Association. Stroke. 2003 Apr;34(4):1056-1083. doi: 10.1161/01.
ehab697. Accessed 14 Jan 2022. PMID: 34791154. STR.0000064841.47697.22. Accessed 16 Apr 2021.
Task Force on Conceptual Model and Preventive Protocols, Adams HP, del Zoppo G, Alberts MJ, et al. Guidelines for the early
Working Group on Primary Care, Hong Kong Food and management of adults with ischemic stroke. A guideline from
Health Bureau. Hong Kong reference framework for the American Heart Association/American Stroke Association
hypertension care for adults in primary care settings. Hong Stroke Council, Clinical Cardiology Council, Cardiovascular
Kong Department of Health. http://www.pco.gov.hk/. 2013. Radiology and Intervention Council, and the Atherosclerotic
Tay JC, Sule AA, Chew EK, et al. Ministry of Health clinical Peripheral Vascular Disease and Quality of Care Outcomes
practice guidelines: hypertension. Singapore Med J. 2018 in Research Interdisciplinary Working Groups. Stroke. 2007
Jan;59(1):17-27. doi: 10.11622/smedj.2018007. Accessed 17 May;38(5):1655-1711. http://stroke.ahajournals.org. PMID:
Dec 2018. PMID: 29376186. 17431204.
The European Society for Cardiology (ESC). ESC guidance Adams HP. Secondary prevention of atherothrombotic events
for the diagnosis and management of CV disease during the after ischemic stroke. Mayo Clin Proc. 2009;84(1):43-51. doi:
COVID-19 pandemic. ESC. https://www.escardio.org. 10 June 10.1016/S0025-6196(11)60807-0. PMID: 19121254.
2020. Accessed 22 Feb 2021. Adams RJ, Albers G, et al. Update to the AHA/ASA
The Multisectoral Task Force Consensus on the Detection and r e co m m e n d at i o n s f o r th e p r e v e nt i o n o f s t r o k e
Management of Hypertension in the Philippines. Philippine in patients with stroke and transient ischemic attack.
clinical practice guidelines on the detection and management Stroke. 2008 May ;39(5):1647-1652. doi: 10.1161/
REFERENCES
of hypertension – 2011 (also known as the 140/90 report). STROKEAHA.107.189063. PMID: 18322260.
Philippine Society of Hypertension. 2012:001-13. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and
Unger T, Borghi C, Charchar F, et al. 2020 International Society thrombolytic therapy for ischemic stroke: American College
of Hypertension global hypertension practice guidelines. of Chest Physicians evidence-based clinical practice guidelines
Hypertension. 2020 Jun;75(6):1334-1357. doi: 10.1161/ (8th edition). Chest. 2008 Jun;133(Suppl 6):630S-669S. PMID:
HYPERTENSIONAHA.120.15026. Accessed 01 Jun 2020. 18574275.
PMID: 32370572. Alberts MJ, Ovbiagele B. Current strategies for ischemic stroke
U.S. Preventive Services Task Force. Screening for high blood prevention: role of multimodal combination therapies. J
pressure: U.S. Preventive Services Task Force reaffirmation Neurol. 2007 Oct;254(10):1414-1426. doi: 10.1007/s00415-
recommendation statement. Ann Intern Med. 2007 007-0569-9. PMID: 17934879.
Dec;147(11):783-786. doi: 10.7326/0003-4819-147-11- Alexandrov AV, Wojner AW, Grotta JC. CLOTBUST: design
200712040-00009. PMID: 18056662. of a randomized trial of ultrasound-enhanced thrombolysis
Van Minh H, Van Huy T, et al. 2018 VNHA/VSH guidelines for for acute ischemic stroke [abstract]. J Neuroimaging. 2004
diagnosis and treatment of hypertension in adults. Vietnam Apr;14(2):108-112. PMID: 15095554.
Heart Association. http://vnha.org.vn. 2018. Accessed 10 Anderson D, Larson D, Bluhm J, et al. Institute for Clinical
May 2019. Systems Improvement. Diagnosis and initial treatment of
Visseren FLJ, Mach F, Smulders YM, et al; ESC National ischemic stroke. ICSI. https://www.icsi.org. Jul 2012.
Cardiac Societies, ESC Scientific Document Group. 2021 Anderson D, Larson D, Sierzant T, et al. Institute for Clinical
ESC guidelines on cardiovascular disease prevention in Systems Improvement. Diagnosis and initial treatment
clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. of ischemic stroke. ICSI. https://www.icsi.org. Jun 2019.
doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021. Accessed 16 Apr 2021.
PMID: 34458905. Andre C, Bacellar AL, Bezerra DD, et al; Executive committee
Weber MA, Schiffrin EL, White WB, et al. Clinical practice from the Brazilian Stroke Society and the Scientific
guidelines for the management of hypertension in the community: Department in Cerebrovascular Diseases of the Brazilian
a statement by the American Society of Hypertension and the Academy of Neurology. Guidelines for acute ischemic stroke
International Society of Hypertension. J Hypertens. 2014 treatment: part II: stroke treatment. Arq Neuropsiquiatr. 2012
Jan;32(1):3-15. doi: 10.1097/HJH.0000000000000065. PMID: Nov;70(11):885-893. doi: 10.1590/s0004-282x2012001100012.
24270181. PMID: 23175203.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/ Antithrombotic Trialists’ Collaboration. Collaborative meta-
AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA analysis of randomised trials of antiplatelet therapy for
guideline for the prevention, detection, evaluation, and prevention of death, myocardial infarction, and stroke in high
management of high blood pressure in adults: a report of the risk patients. BMJ. 2002 Jan;324(7329):71-86. doi: 10.1136/
American College of Cardiology/American Heart Association bmj.324.7329.71. PMID: 11786451.
Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Baerlocher MO, Asch M, Myers A. Five things to know
2018 May 15;71(19):e127-e248. doi: 10.1016/j.jacc.2017.11.006. about metformin and intravenous contrast. CMAJ. 2013
PMID: 29146535. Jan;185(1):E78. doi: 10.1503/cmaj.090550. Accessed 17 Jun
Whitworth JA; World Health Organization, International 2019. PMID: 23048079.
Society of Hypertension Writing Group. 2003 World Health Beghi E, Binder H, Birle C, et al. European Academy of
Organization (WHO)/International Society of Hypertension Neurology and European Federation of Neurorehabilitation
(ISH) statement on management of hypertension. J Hypertens. Societies guideline on pharmacological support in early
2003 Nov;21(11):1983-1992. doi: 10.1097/00004872- motor rehabilitation after acute ischaemic stroke. Eur J
200311000-00002. PMID: 14597836. Neurol. 2021 Sep;28(9):2831-2845. doi: 10.1111/ene.14936.
Williams B, Mancia G, Spiering W, et al; The Task Force for PMID: 34152062.
the Management of Arterial Hypertension of the European Berge E, Whiteley W, Audebert H, et al. European Stroke
Society of Cardiology (ESC) and the European Society of Organisation (ESO) guidelines on intravenous thrombolysis
Hypertension (ESH). 2018 ESC/ESH guidelines for the for acute ischaemic stroke. Eur Stroke J. 2021 Mar;6(1):I-LXII.
management of arterial hypertension. ESC. https://www. doi: 10.1177/2396987321989865. Accessed 19 Apr 2022.
escardio.org. 2018. Accessed 25 Aug 2018. PMID: 33817340.
Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and
treatment of hypertriglyceridemia: an Endocrine Society
Ischemic Stroke clinical practice guideline. J Clin Endocrinol Metab. 2012
Adams HP Jr, Adams RJ, Brott T, et al. Guidelines for the early Sep;97(9):2969-2989. doi: 10.1210/jc.2011-3213. PMID:
management of patients with ischemic stroke: a scientific 22962670.
statement from the Stroke Council of the American Stroke Biller J, Schneck M. Vascular diseases of the nervous system:
ischemic cerebrovascular disease. In: Bradley W, Daroff R,
281
Fenichel G, et al. Bradley: Neurology I Clinical Practice. 5th Fugate JE, Rabinstein AA. Absolute and relative contraindications
ed. Philadelphia: Butterworth Heinemann Elsevier; 2008. to IV rt-PA for acute ischemic stroke. Neurohospitalist. 2015
http://www.mdconsult.com. Jul;5(3):110-121. doi: 10.1177/1941874415578532. PMID:
Biller J. Antiplatelet therapy in ischemic stroke: variability in 26288669.
clinical trials and its impact on choosing the appropriate Furie KL, Goldstein LB, Albers GW, et al; American Heart
therapy. J Neurol Sci. 2009 Sep;284:1-9. doi: 10.1016/j. Association Stroke Council; Council on Quality of Care and
jns.2009.04.001. PMID: 19380153. Outcomes Research; Council on Cardiovascular Nursing;
Camm AJ, Lip GY, De Caterina R, et al; ESC Committee for Council on Clinical Cardiology; Council on Peripheral
Practice Guidelines (CPG). 2012 focused update of the Vascular Disease. Oral antithrombotic agents for the
ESC guidelines for the management of atrial fibrillation: an prevention of stroke in nonvalvular atrial fibrillation: a science
update of the 2010 ESC guidelines for the management of advisory for healthcare professionals from the American
atrial fibrillation. Developed with the special contribution Heart Association/American Stroke Association. Stroke.
of the European Heart Rhythm Association. Eur Heart J. 2012 Dec;43(12):3442-3453. http://stroke.ahajournals.org/.
2012;33(21):2719-2747. http://www.escardio.org. PMID: PMID: 22858728.
22922413. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention
Campbell BCV, Ma H, Ringleb PA, et al; EXTEND, ECASS-4, of stroke in patients with stroke or transient ischemic attack.
and EPITHET Investigators. Extending thrombolysis to 4·5-9 A guideline for healthcare professionals from the American
h and wake-up stroke using perfusion imaging: a systematic Heart Association/American Stroke Association. Stroke.
2011 Jan;42(1):227-276. http://stroke.ahajournals.org. PMID:
REFERENCES
review and meta-analysis of individual patient data. Lancet.

2019 Jul 13;394(10193):139-147. doi: 10.1016/S0140- 20966421.
6736(19)31053-0. Accessed 18 Apr 2022. PMID: 31128925. Guyatt GH, Akl EA, Crowther M, et al. Executive summary:
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus antithrombotic therapy and prevention of thrombosis, 9th ed:
warfarin in patients with atrial fibrillation. N Engl J Med. American College of Chest Physicians evidence-based clinical
2009 Sep;361(12):1139-1151. doi: 10.1056/NEJMoa0905561. practice guidelines. Chest. 2012 Feb;141(Suppl 2):7S-47S.
PMID: 19717844. http://www.chestnet.org. PMID: 22315257.
Coull BM, Williams LS, Goldstein LB, et al. Anticoagulants and Heidbuchel H, Verhamme P, Alings M, et al. Updated European
antiplatelet agents in acute ischemic stroke: report of the Joint Heart Rhythm Association practical guide on the use of non-
Stroke Guideline Development Committee of the American vitamin K antagonist anticoagulants in patients with non-
Academy of Neurology and the American Stroke Association valvular atrial fibrillation. Europace. 2015 Oct;17(10):1467-
(a division of the American Heart Association). Stroke. 2002 1507. doi: 10.1093/europace/euv309. PMID: 26324838.
Jul;33(7):1934-1942. doi: 10.1161/01.str.0000028456.18614.93. Hindricks G, Potpara T, Dagres N, et al; ESC Scientific
PMID: 12105379. Document Group. 2020 ESC guidelines for the diagnosis and
Crocco TJ, Meurer WJ. Stroke. In: Walls RM, Hockberger RS, management of atrial fibrillation developed in collaboration
Gausche-Hill M, eds. Rosen’s Emergency Medicine: Concepts with the European Association of Cardio-Thoracic Surgery
and Clinical Practice. 9th ed. Philadelphia, PA: Elsevier; 2018. (EACTS). Eur Heart J. 2021 Feb;42(5):373-498. doi: 10.1093/
Accessed 25 Jun 2018:1241-1255. eurheartj/ehaa612. Accessed 16 Apr 2021. PMID: 32860505.
Culebras A, Messé SR, Chaturvedi S, et al. Summary of Huang Y, Cheng Y, Wu J, et al. Cilostazol as an alternative to
evidence-based guideline update: prevention of stroke aspirin after ischaemic stroke: a randomised, double-blind,
in nonvalvular atrial fibrillation: report of the Guideline pilot study. Lancet Neurol. 2008 Jun;7(6):494-499. doi:
Development Subcommittee of the American Academy of 10.1016/S1474-4422(08)70094-2. PMID: 18456558.
Neurology. Neurology. 2014 Feb;82(8):716-724. doi: 10.1212/ Jauch EC, Saver JL, Adams HP Jr, et al; American Heart
WNL. 0000000000000145. PMID: 24566225. Association Stroke Council; Council on Cardiovascular
Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the Nursing; Council on Peripheral Vascular Disease; Council on
time window for treatment of acute ischemic stroke with Clinical Cardiology. Guidelines for the early management of
intravenous tissue plasminogen activator: a science advisory patients with acute ischemic stroke: a guideline for healthcare
from the American Heart Association/American Stroke professionals from the American Heart Association/
Association. Stroke. 2009 Aug;40(8):2945-2948. doi: 10.1161/ American Stroke Association. Stroke. 2013 Mar;44(3):870-
STROKEAHA.109.192535. PMID: 19478221. 947. http://stroke.ahajournals.org. PMID: 23370205.
Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al; Jellinger PS, Smith DA, Mehta AE, et al; AACE Task
American Heart Association Stroke Council and Council Force for Management of Dyslipidemia and Prevention
on Epidemiology and Prevention. Scientific rationale for the of Atherosclerosis. American Association of Clinical
inclusion and exclusion criteria for intravenous alteplase in Endocrinologists’ guidelines for management of dyslipidemia
acute ischemic stroke: a statement for healthcare professionals and prevention of atherosclerosis. Endocr Pract. 2012
from the American Heart Association/American Stroke Mar;18(Suppl 1):1-78. https://www.ncbi.nlm.nih.gov. PMID:
Association. Stroke. 2016 Feb;47(2):581-641. doi: 10.1161/ 22522068.
STR.0000000000000086. PMID: 26696642. Jianu DC, Muresanu DF, Bajenaru O, et al. Cerebrolysin adjuvant
Dennis M, Caso V, Kappelle LJ, et al; for the European Stroke treatment in Broca’s aphasics following first acute ischemic
Organization. European Stroke Organization (ESO) guidelines stroke of the left middle cerebral artery. J Med Life. 2010
for prophylaxis for venous thromboembolism in immobile Jul;3(3):297-307. PMID: 20945821.
patients with acute ischaemic stroke. European Stroke Journal. Katzan IL. Antiplatelets in secondary stroke prevention.
2016 Mar;1(1):6-19. http://www.eso-stroke.org. PMID: Cleveland Clinic. http://www.clevelandclinicmeded.com.
31008263. Jan 2009.
Diener HC, Weimar C, Weber R. Antiplatelet therapy in Kernan WN, Ovbiagale B, Black HR, et al. Guidelines for the
secondary stroke prevention – state of that art. J Cell prevention of stroke in patients with stroke and transient
Med. 2010 Nov;14(11):2552-2560. doi: 10.1111/j.1582- ischemic attack: a guideline for healthcare professionals
4934.2010.01163.x. Accessed 16 Apr 2021. from the American Heart Association/American Stroke
European Stroke Organisation. Guidelines for management of Association. Stroke. 2014 Jul;45(7):2160-2236. http://stroke.
ischaemic stroke and transient ischaemic attack. ESO. http:// ahajournals.org. PMID: 24788967.
www.eso-stroke.org. Mar 2008. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines
Family Practice Notebook. Ischemic stroke. Family Practice for the management of atrial fibrillation developed in
Notebook. https://www.fpnotebook.com/. Accessed 16 Apr collaboration with EACTS. Eur Heart J. 2016 Oct;37(38):2893-
2021. 2962. doi: 10.1093/eurheartj/ehw210. PMID: 27567408.
282
Ladurner G, Kalvach P, Moessler H. Neuroprotective treatment National Stroke Foundation. Clinical guidelines for
with cerebrolysin in patients with acute stroke: a randomised stroke management 2010. Stroke Foundation. http://
controlled trial. J Neural Transm. 2005 Mar;112(3):415-428. strokefoundation.com.au. Sep 2010.
http://www.ncbi.nlm.nih.gov. PMID: 15583955. Ng PW, Huang CY, et al. Consensus statement on ischaemic
L ane DA , Lip GY. Use of the C H A2DS2-VA Sc and stroke care in Hong Kong. Hong Kong Med J. 2004
H A S -BLED scores to aid decision making for Apr;10(2):124-129. PMID: 15075433.
thromboprophylaxis in nonvalvular atrial fibrillation. Ona DID, Jimeno CA, Jasul GV, et al. Executive summary of
Circulation. 2012 Aug;126(7):860-865. doi: 10.1161/ the 2020 clinical practice guidelines for the management
CIRCULATIONAHA.111.060061. PMID: 22891166. of hypertension in the Philippines. J Clin Hypertens
Lau G, Pendlebury S, Rothwell P. The clinical features and (Greenwich). 2021 Aug 3:1-14. doi: 10.1111/jch.14335.
differential diagnosis of acute stroke. Transient Ischemic Accessed 05 Aug 2021. PMID: 34343391.
Attack and Stroke: Diagnosis, Investigation and Treatment. Ortel TL. Chapter 42 - Antithrombotic therapy. In: McPherson
Cambridge: Cambridge University Press; 2018. Accessed 02 RA, Pincus MR. Henry’s Clinical Diagnosis and Management
Oct 2018:139-158. by Laboratory Methods. 23rd edition; 2017. http://dx.doi.
Lee WH, Chu CY, Hsu PC, et al. Comparison of antiplatelet and org/10.1016/B978-0-323-29568-0.00042-5. Accessed 26 Jun
antithrombotic therapy for secondary prevention of ischemic 2018:842-853.e2.
stroke in patients with peripheral artery disease: population- Paciaroni M, Bogousslavsky J. Primary and secondary
based follow-up study in Taiwan. Circ J. 2012;77(4):1046- prevention of ischemic stroke. Eur Neurol. 2010;63(5):267-
REFERENCES
1052. http://jstage.jst.go.jp. PMID: 23269006. 278. doi: 10.1159/000285183. PMID: 20357456.
Lindsay P, Bayley M, McDonald A, et al. Toward a more effective Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta Stroke
approach to stroke: Canadian Best Practice Recommendations Program Early CT Score (ASPECTS) for assessing CT scans
for Stroke Care. CMAJ. 2008 May;178(1):1418-1425. doi: in patients with acute stroke. AJNR Am J Neuroradiol. 2001
10.1503/cmaj.071253. PMID: 18490636. Sep;22(8):1534-1542. http://www.ajnr.org. PMID: 11559501.
Lip GYH, Banergee A, Boriani G, et al. Antithrombotic therapy Phipps MS, Cronin CA. Management of acute ischemic stroke.
for atrial fibrillation. CHEST Guideline and Expert Panel BMJ. 2020 Feb 13;368:l6983. doi: 10.1136/bmj.l6983. Accessed
report. Chest. 2018 Nov;154(5):1121-1201. doi: 10.1016/j. 02 Sep 2020. PMID: 32054610.
chest.2018.07.040. Accessed 16 Apr 2021. PMID: 30144419. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart
Maegdefessel L, Spin JM, Azuma J, et al. New options with Association/American Stroke Association focused update
dabigatran etexilate in anticoagulant therapy. Vasc Health of the 2013 guidelines for the early management of patients
Risk Manag. 2010 May;6:339-349. http://www.ncbi.nlm.nih. with acute ischemic stroke regarding endovascular treatment:
gov. PMID: 20531953. a guideline for healthcare professionals from the American
Malaysian Society of Neurosciences, Academy of Medicine Heart Association/American Stroke Association. Stroke. 2015
Malaysia, Ministry of Health Malaysia, MSN Stroke Council. Oct;46(10):3020-3035. doi: 10.1161/STR.0000000000000074.
Clinical practice guidelines. Management of ischaemic stroke. PMID: 26123479.
3rd edition. MOH (Malaysia). https://www.moh.gov.my. 2020. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for
Accessed 09 Mar 2021. the early management of patients with acute ischemic stroke:
Manning WJ, Singer DE, Lip GYH. Atrial fibrillation: 2019 update to the 2018 guidelines for the early management of
anticoagulant therapy to prevent thromboembolism. acute ischemic stroke: a guideline for healthcare professionals
UpToDate. https://www.uptodate.com. 27 Oct 2020. from the American Heart Association/American Stroke
Marks MP, Heit JJ, Lansberg MG, et al. Endovascular treatment Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/
in the DEFUSE 3 study. Stroke. 2018 Jul 9;49:2000-2003. doi: STR.0000000000000211. Accessed 18 Apr 2022. PMID:
10.1161/STROKEAHA.118.022147. Accessed 12 Oct 2018. 31662037.
PMID: 29986935. Powers WJ, Rabinstein AA, Ackerson T, et al; American
Meschia JF, Bushnell C, Boden-Albala B, et al; American Heart Heart Association Stroke Council. 2018 Guidelines for the
Association Stroke Council; Council on Cardiovascular and early management of patients with acute ischemic stroke:
Stroke Nursing; Council on Clinical Cardiology; Council on a guideline for healthcare professionals from the American
Functional Genomics and Translational Biology; Council Heart Association/American Stroke Association. Stroke. 2018
on Hypertension. Guidelines for the primary prevention Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158.
of stroke: a statement for healthcare professionals from the Accessed 17 Apr 2018. PMID: 29367334.
American Heart Association/American Stroke Association. Saccor RL, Kasner SE, Broderick JP, et al. An updated definition
Stroke. 2014 Dec;45(12):3754-3832. http://stroke.ahajournals. of stroke for the 21st century: a statement for healthcare
org. PMID: 25355838. professionals from the American Heart Association/
Minematsu K, Toyoda K, Hirano T, et al. Guidelines for American Stroke Association. Stroke. 2013 Jul;44(7):2064-
the intravenous application of recombinant tissue-type 2089. doi: 10.1161/STR.0b013e318296aeca. PMID: 23652265.
plasminogen activator (alteplase), the second edition, October Scottish Intercollegiate Guidelines Network. Management
2012: a guideline from the Japan Stroke Society. J Stroke of patients with stroke: rehabilitation, prevention and
Cerebrovasc Dis. 2013 Jul;22(5):571-600. doi: 10.1016/j. management of complications, and discharge planning. SIGN.
jstrokecerebrovasdis.2013.04.001. PMID: 23727456. http://www.sign.ac.uk. Jun 2010.
Ministry of Health Malaysia. Clinical practice guidelines: Sherman DG. Stroke prevention in atrial fibrillation:
management of stroke. Academy of Medicine of Malaysia. pharmacological rate versus rhythm control. Stroke. 2007
http://www.acadmed.org.my. 2006. Feb;38(Suppl 2):615-617. http://stroke.ahajournals.org. PMID:
Ministry of Health Singapore. Clinical practice guidelines. 17261701.
Stroke and transient ischaemic attacks: assessment, Shulga O, Bornstein N. Antiplatelets in secondary stroke
investigation, immediate management and secondary prevention. Front Neurol. 2011 Jul;2(36). http://www.ncbi.
prevention. MOH (Singapore). http://www.moh.gov.sg. nlm.nih.gov. PMID: 21772826.
Jul 2009.
Smith EE, Saposnik G, Biessels GJ, et al; American Heart
National Collaborating Centre for Chronic Conditions (UK). Association Stroke Council; Council on Cardiovascular
Stroke: diagnosis and initial management of acute stroke Radiology and Intervention; Council on Functional Genomics
and transient ischaemic attack (TIA). NICE. https://www. and Translational Biology; and Council on Hypertension.
nice.org.uk. 2008. Prevention of stroke in patients with silent cerebrovascular
National Institute for Health and Care Excellence. Dabigatran disease: a scientific statement for healthcare professionals
etexilate for the prevention of stroke and systemic embolism from the American Heart Association/American Stroke
in atrial fibrillation. NICE. http://www.nice.org.uk. 2012.
283
Association. Stroke. 2017 Feb;48(2):e44-e71. doi: 10.1161/ Myocardial Infarction w/ ST-Segment
STR.0000000000000116. PMID: 27980126.
Summers D, Leonard A, Wentworth D, et al. Comprehensive
Elevation
overview of nursing and interdisciplinary care of the acute Academy of Medicine Malaysia, Ministry of Health Malaysia,
ischemic stroke patient: a scientific statement from the National Heart Association of Malaysia. Clinical practice
American Heart Association. Stroke. 2009 Aug;40(8):2911- guideline: management of acute ST segment elevation
2944. doi: 10.1161/STROKEAHA.109.192362. PMID: myocardial infarction (STEMI). 4th edition. National Heart
19478222. Association of Malaysia. https://www.malaysianheart.org. 22
The American Heart Association. 2005 International Consensus Nov 2019. Accessed 27 Nov 2019.
Conference on cardiopulmonary resuscitation (CPR) and Academy of Medicine Malaysia, Ministry of Health Malaysia,
emergency cardiovascular care (ECC) science with treatment National Heart Association of Malaysia. CPG slides summary
recommendations. Part 9: stroke. Circulation. 2005;112:III- - management of acute ST segment elevation myocardial
110-III-104. http://circ.ahajournals.org. infarction (STEMI) 2019. 4th edition. National Heart
The Stroke Society of the Philippines. Guidelines for the Association of Malaysia. https://www.malaysianheart.org.
Prevention, Treatment and Rehabilitation of Stroke. 5th 2019. Accessed 30 Apr 2019.
ed. Quezon City, Philippines: The Stroke Society of the Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction
Philippines; 2010:10-111. redefined--a consensus document of The Joint European
The Stroke Society of the Philippines. SSP Handbook of Stroke: Society of Cardiology/American College of Cardiology
REFERENCES
Guidelines for the Prevention, Treatment and Rehabilitation Committee for the redefinition of myocardial infarction.
of Stroke. 6th ed. Quezon City, Philippines: The Stroke Society J Am Coll Cardiol. 2000 Sep;36(3):959-969. doi: 10.1016/
of the Philippines; 2014:11-121. s0735-1097(00)00804-4. PMID: 10987628.
Van der Worpp HB, van Gijn J. Acute ischemic stroke. N Engl J Antman EM, Anbe DT, Armstrong PW, et al; American
Med. 2007 Aug;357(6):572-579. doi: 10.1056/NEJMcp072057. College of Cardiology; American Heart Association;
PMID: 17687132. Canadian Cardiovascular Society. ACC/AHA guidelines for
the management of patients with ST-elevation myocardial
Visseren FLJ, Mach F, Smulders YM, et al; ESC National
infarction-executive summary. A report of the American
Cardiac Societies, ESC Scientific Document Group. 2021
College of Cardiology/American Heart Association Task
ESC guidelines on cardiovascular disease prevention in
Force on Practice Guidelines (Writing Committee to revise
clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337.
the 1999 guidelines for the management of patients with
doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021.
acute myocardial infarction). J Am Coll Cardiol. 2004
PMID: 34458905.
Aug;44(3):671-719. doi: 10.1016/j.jacc.2004.07.002. PMID:
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in 15358045.
acute minor stroke or transient ischemic attack. N Eng J
Antman EM, Hand M, Armstrong PW, et al; Canadian
Med. 2013 Jul;369(1):11-19. doi: 10.1056/NEJMoa1215340.
Cardiovascular Society; American Academy of Family
PMID: 23803136.
Physicians; American College of Cardiology; American Heart
Wann LS, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/ Association. 2007 Focused update of the ACC/AHA 2004
AHA/HRS focused update on the management of patients guidelines for the management of patients with ST-elevation
with atrial fibrillation (update on dabigatran): a report of myocardial infarction: a report of the American College
the American College of Cardiology Foundation/American of Cardiology/American Heart Association Task Force on
Heart Association Task Force on practice guidelines. J Am Practice Guidelines. J Am Coll Cardiol. 2008 Jan;51(2):210-
Coll Cardiol. 2011 Mar;57(11):1330-1337. doi: 10.1016/j. 247. doi: 10.1016/j.jacc.2007.10.001. PMID: 18191746.
jacc.2011.01.010. PMID: 21324629.
Bell AD, Roussin A, Cartier R, et al. Canadian Cardiovascular
Winstein CJ, Stein J, Arena R, et al; American Heart Association Society antiplatelet guideline 2010. Canadian Cardiovascular
Stroke Council, Council on Cardiovascular and Stroke Society. http://www.ccsguidelineprograms.ca/. 2010.
Nursing, Council on Clinical Cardiology, and Council
Bertrand ME, Simoons ML, Fox KA, et al; Task Force on the
on Quality of Care and Outcomes Research. Guidelines
Management of Acute Coronary Syndromes of the European
for adult stroke rehabilitation and recovery: a guideline
Society of Cardiology. Management of acute coronary
for healthcare professionals from the American Heart
syndromes in patients presenting without persistent ST-
Association/American Stroke Association. Stroke. 2016
segment elevation. Eur Heart J. 2002 Dec;23(23):1809-1840.
Jun;47(6):e98-e169. doi: 10.1161/STR.0000000000000098.
doi: 10.1053/euhj.2002.3385. PMID: 12503543.
PMID: 27145936.
Beygui F, Castren M, Brunetti ND, et al. Pre-hospital
Xu AD, Wang YJ, Wang DZ; Chinese Stroke Therapy Expert
management of patients with chest pain and/or dyspnoea of
Panel for Intravenous Recombinant Tissue Plasminogen
cardiac origin. A position paper of the Acute Cardiovascular
Activator. Consensus statement on the use of intravenous
Care Association (ACCA) of the ESC. Eur Heart J Acute
recombinant tissue plasminogen activator to treat acute
ischemic stroke by the Chinese Stroke Therapy Expert Panel. Cardiovasc Care. 2020 Mar;9(1_suppl):59-81. doi:
CNS Neurosci Ther. 2013 Aug;19(8):543-548. doi: 10.1111/ 10.1177/2048872615604119. Accessed 24 Feb 2022. PMID:
cns.12126. PMID: 23710819. 26315695.
Yee AH, Rabinstein AA. Neurologic presentations of acid- Chandrashekhar Y, Alexander T, Mullasari A, et al. Resource
base imbalance, electrolyte abnormalities, and endocrine and infrastructure-appropriate management of ST-segment
emergencies. Neurol Clin. 2010 Feb;28(1):1-16. doi: 10.1016/j. elevation myocardial infarction in low- and middle-income
ncl.2009.09.002. Accessed 17 Jun 2019. PMID: 19932372. countries. Circulation. 2020 Jun 16;141(24):2004-2025. doi:
10.1161/CIRCULATIONAHA.119.041297. Accessed 23 Feb
Yew KS, Cheng E. Acute stroke diagnosis. Am Fam Physician. 2022. PMID: 32539609.
2009 Jul;80(1):33-40. https://www.aafp.org. PMID: 19621844.
Collet JP, Thiele H, Barbato E, et al. 2020 ESC guidelines for
Zhang C. Cerebrolysin enhances neurogenesis in the ischemic the management of acute coronary syndromes in patients
brain and improves functional outcome after stroke. J presenting without persistent ST-segment elevation. 29 Aug
Neurosci Res. 2010 Nov;88(15):3275-3281. http://www.ncbi. 2020. doi: 10.1093/eurheartj/ehaa575. Accessed 01 Sep 2020.
nlm.nih.gov. PMID: 20857512. PMID: 32860058.
Goodman SG, Menon V, Cannon CP, et al. Acute ST-segment
elevation myocardial infarction. American College of Chest
Physicians evidence-based clinical practice guidelines. 8th
284
ed. Chest. 2008 Jun;133(Suppl 6):708S-775S. doi: 10.1378/ myocardial infarction (STEMI). 2nd ed. Ministry of Health
chest.08-0665. PMID: 18574277. Malaysia. http://www.moh.gov.my. 2007.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/ National Institute for Health and Care Excellence (NICE). Acute
CHEST/SAEM/SCCT/SCMR guideline for the evaluation coronary syndromes. NICE. https://www.nice.org.uk. 18 Nov
and diagnosis of chest pain. A report of the American 2020. Accessed 18 Dec 2021.
College of Cardiology/American Heart Association Joint O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA
Committee on clinical practice guidelines. Circulation. 2021 guideline for the management of ST-elevation myocardial
Nov;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029. infarction: a report of the American College of Cardiology
Accessed 18 Dec 2021. PMID: 34709879. Foundation/American Heart Association Task Force on
Ibanez B, James S, Agewall S, et al. 2017 ESC guidelines for Practice Guidelines. Circulation. 2013 Jan;127(4):e362-e425.
the management of acute myocardial infarction in patients doi: 10.1161/CIR.0b013e3182742cf6. PMID: 23247304.
presenting with ST-segment elevation: The Task Force for Ohman EM, Harrington RA, Cannon CP, et al. Intravenous
the management of acute myocardial infarction in patients thrombolysis in acute myocardial infarction. Chest. 2001
presenting with ST-segment elevation of the European Jan;119(Suppl 1):253S-277S. doi: 10.1378/chest.119.1_
Society of Cardiology (ESC). Eur Heart J. 2018 Jan;39(2):119- suppl.253s. PMID: 11157653.
177. doi: 10.1093/eurheartj/ehx393. Accessed 26 Aug 2020. Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/
PMID: 28886621. ASE/ASNC/SCAI/SCCT/STS 2016 appropriate use criteria
Knuuti J, Wijns W, Saraste A, et al. 2019 ESC guidelines for the for coronary revascularization in patients with acute coronary
REFERENCES
diagnosis and management of chronic coronary syndromes: syndromes: a report of the American College of Cardiology
The Task Force for the diagnosis and management of chronic Appropriate Use Criteria Task Force, American Association
coronary syndromes of the European Society of Cardiology for Thoracic Surgery, American Heart Association, American
(ESC). Eur Heart J. 2019:1-71. doi: 10.1093/eurheartj/ehz425. Society of Echocardiography, American Society of Nuclear
Accessed 10 Sep 2019. PMID: 31504439. Cardiology, Society for Cardiovascular Angiography
Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused updates: and Interventions, Society of Cardiovascular Computed
ACC/AHA guidelines for the management of patients Tomography, and the Society of Thoracic Surgeons. J
with ST-elevation myocardial infarction (updating the Am Coll Cardiol. 2017 Feb;69(5):570-591. doi: 10.1016/j.
2004 guideline and 2007 focused update) and ACC/AHA/ jacc.2016.10.034. PMID: 28012615.
SCAI guidelines on percutaneous coronary intervention Philippine Heart Association CAD Guidelines Writing
(updating the 2005 guideline and 2007 focused update): a Committee. 2014 PHA clinical practice guidelines for the
report of the American College of Cardiology Foundation/ diagnosis and management of patients with coronary artery
American Heart Association Task Force on Practice disease. Philippine Heart Association. http://www.philheart.
Guidelines. Circulation. 2009 Dec;120(22):2271-2306. doi: org/. 27 Nov 2014.
10.1161/CIRCULATIONAHA.109.192663. PMID: 19923169. Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for
Lawton JS, Tamis-Holland JE, Bangalore S. 2021 ACC/AHA/ the management of acute coronary syndromes in patients
SCAI guideline for coronary artery vascularization. A report presenting without persistent ST-segment elevation – web
of the American College of Cardiology/American Heart addenda: Task Force for the Management of Acute Coronary
Association Joint Committee on clinical practice guidelines. Syndromes in Patients Presenting without Persistent ST-
Circulation. 2021 Dec;CIR0000000000001039. doi: 10.1161/ Segment Elevation of the European Society of Cardiology
CIR.0000000000001039. Accessed 18 Dec 2021. PMID: (ESC). European Society of Cardiology. https://www.escardio.
34882436. org/. 2015.
Levine GN, Bates ER, Bittl JA, et al; Focused Update Writing Task Force on the management of ST-segment elevation
Group. 2016 ACC/AHA guideline focused update on duration acute myocardial infarction of the European Society of
of dual antiplatelet therapy in patients with coronary artery Cardiology (ESC). ESC Guidelines for the management of
disease: a report of the American College of Cardiology/ acute myocardial infarction in patients presenting with ST-
American Heart Association Task Force on Clinical Practice segment elevation. Eur Heart J. 2012 Oct;33(20):2569-2619.
Guidelines. J Am Coll Cardiol. 2016 Mar 23:pii: S0735- doi: 10.1093/eurheartj/ehs215. PMID: 22922416.
1097(16)01699-5. doi: 10.1016/j.jacc.2016.03.513. PMID: Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition
27036918. of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-
Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/ 2567. doi: 10.1093/eurheartj/ehs184. PMID: 22922414.
SCAI focused update on primary percutaneous coronary Thygesen K, Alpert JS, Jaffe AS, et al; ESC Scientific Document
intervention for patients with ST-elevation myocardial Group. Fourth universal definition of myocardial infarction
infarction: an update of the 2011 ACCF/AHA/SCAI (2018). Eur Heart J. 2019 Jan 14;40(3):237-269. doi: 10.1093/
guideline for percutaneous coronary intervention and the eurheartj/ehy462. Accessed 12 Mar 2019. PMID: 30165617.
2013 ACCF/AHA guideline for the management of ST-
elevation myocardial infarction: a report of the American Tofield A. Pharmaco-invasive vs. facilitated percutaneous
College of Cardiology/American Heart Association Task coronary intervention strategies for ST-segment-elevation
Force on Clinical Practice Guidelines and the Society acute myocardial infarction patients in the new ESC
for Cardiovascular Angiography and Interventions. Guidelines. Eur Heart J. 2009 Dec;30(23):2817. doi: 10.1093/
Circulation. 2015 Mar;133(11):1135-1147. doi: 10.1161/ eurheartj/ehp409. PMID: 19952008.
CIR.0000000000000336. PMID: 26490017. Valgimigli M, Bueno H, Byrne RA, et al; ESC Scientific
Ma M, Bu L, Shi L, et al. Effect of loading dose of atorvastatin Document Group; ESC Committee for Practice Guidelines
therapy prior to percutaneous coronary intervention in (CPG); ESC National Cardiac Societies. 2017 ESC focused
patients with acute coronary syndrome: a meta-analysis update on dual antiplatelet therapy in coronary artery disease
of six randomized controlled trials. Drug Des Devel Ther. developed in collaboration with EACTS: The Task Force for
2019;13:1233-1240. Accessed 23 Feb 2022. PMID: 31354240. dual antiplatelet therapy in coronary artery disease of the
European Society of Cardiology (ESC) and of the European
Ministry of Health Malaysia, National Heart Association Association for Cardio-Thoracic Surgery (EACTS). Eur Heart
Malaysia, Academy of Medicine Malaysia. Clinical practice J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419.
guidelines: management of acute ST segment elevation Accessed 15 Jan 2018. PMID: 28886622.
myocardial infarction (STEMI) 2014 - 3rd edition. Ministry
Van de Werf F, Ardissino D, Betriu A, et al. Management of
of Health Malaysia. http://www.moh.gov.my/. 2014.
acute myocardial infarction in patients presenting with
Ministry of Health Malaysia, National Heart Association of ST-segment elevation. The Task Force on the Management
Malaysia, Academy of Medicine Malaysia. Clinical practice of Acute Myocardial Infarction of the European Society of
guidelines on management of acute ST segment elevation
285
Cardiology. Eur Heart J. 2003 Jan;24(1):28-66. doi: 10.1016/ Thoracic Society guidelines for the management of suspected
s0195-668x(02)00618-8. PMID: 12559937. acute pulmonary embolism. Thorax. 2003 Jun;58(6):470-484.
Van de Werf F, Bax J, Betriu A, et al. Management of acute PMID: 12775856.
myocardial infarction in patients presenting with persistent Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy
ST-segment elevation: The Task Force on the Management for venous thromboembolic disease: the seventh ACCP
of ST-Segment Elevation Acute Myocardial Infarction conference on antithrombotic and thrombolytic therapy.
of the European Society of Cardiology. Eur Heart J. 2008 Chest. 2004 Sep;126(3 Suppl):401S-428S. PMID: 15383479.
Dec;29(23):2909-2945. doi: 10.1093/eurheartj/ehn416. Creager MA, Dzau VJ. Vascular diseases of the extremities.
PMID: 19004841. In: Fauci AS, Braunwald E, Isselbacher KJ, et al. Harrison’s
Visseren FLJ, Mach F, Smulders YM, et al; ESC National Principles of Internal Medicine. 14th ed: McGraw-Hill;
Cardiac Societies, ESC Scientific Document Group. 2021 1998:1404-1405.
ESC guidelines on cardiovascular disease prevention in Dupras D, Bluhm J, Felty C, et al. Institute for Clinical
clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. Systems Improvement (ICSI). Health care guideline: venous
doi: 10.1093/eurheartj/ehab484. Accessed 15 Dec 2021. thromboembolism diagnosis and treatment. 13th ed. ICSI.
PMID: 34458905. https://www.icsi.org. Jan 2013.
Wong GC, Welsford M, Ainsworth C, et al. 2019 Canadian Fesmire FM, Kline JA, Wolf SJ, et al. Clinical policy: critical
Cardiovascular Society/Canadian Association of Interventional issues in the evaluation and management of adult patients
Cardiology guidelines on the acute management of ST-elevation presenting with suspected lower-extremity deep venous
thrombosis. Ann Emerg Med. 2003 Jul;42(1):124-135. http://
REFERENCES
myocardial infarction: focused update on regionalization and

reperfusion. Can J Cardiol. 2019 Feb;35(2):107-132. doi: dx.doi.org/10.1067/mem.2003.181. PMID: 12827132
10.1016/j.cjca.2018.11.031. Accessed 12 Mar 2019. PMID: Goldhaber SZ. Modern treatment of pulmonary embolism.
30760415. Eur Respir J Suppl. 2002 Feb;35:22S-27S. PMID: 12064677
Yildiz M, Wade SR, Henry TD. STEMI care 2021: addressing Goldhaber SZ. Pulmonary embolism. In: Mann DL. Braunwald’s
the knowledge gaps. Am Heart J Plus. 2021 Nov;11:100044. Heart Disease: A Textbook of Cardiovascular Medicine. 10th
doi: 10.1016/j.ahjo.2021.100044. Accessed 18 Dec 2021. ed. Philadelphia: PA: Saunders, Elsevier; 2015:1664-1681.
PMID: 34664037. Henke PK, Kahn SR, Pannucci CJ, et al. Call to action to
prevent venous thromboembolism in hospitalized patients:
a policy statement from the American Heart Association.
Venous Thromboembolism - Management Circulation. 2020 Jun 16;141(24):e914-e931. doi: 10.1161/
Almoosa, K. Is thrombolytic therapy effective for pulmonary CIR.0000000000000769. Accessed 21 Apr 2022. PMID:
embolism? Am Fam Physician. 2002 Mar;65(6):1097-1102. 32375490.
PMID: 11925086 Hirsh J, Anand SS, Halperin JL, et al. AHA scientific
American College of Emergency Physicians (ACEP) Clinical statement: guide to anticoagulant therapy: heparin: a
Policies Committee; ACEP Clinical Policies Subcommittee statement for healthcare professionals from the American
on Suspected Lower-Extremity Deep Venous Thrombosis. Heart Association. Arterioscler Thromb Vasc Biol. 2001
Clinical policy: critical issues in the evaluation and Jul;21(7):E9-9. doi: 10.1161/hq0701.093520. Accessed 13 May
management of adult patients presenting with suspected 2022. PMID: 11451763.
lower-extremity deep venous thrombosis. Ann Emerg Med. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and
2003 Jul;42(1):124-135. PMID: 12827132 low-molecular-weight heparin: mechanisms of action,
American College of Emergency Physicians Clinical Policies pharmacokinetics, dosing, monitoring, efficacy, and safety.
Committee; Clinical Policies Committee Subcommittee on Chest. 2001 Jan;119(1 Suppl):S64-S94. PMID: 11157643.
Suspected Pulmonary Embolism. Clinical policy: critical Hong J, Ahn SY, Lee YJ, et al. Updated recommendations for
issues in the evaluation and management of adult patients the treatment of venous thromboembolism. Blood Res. 2021
presenting with suspected pulmonary embolism. Ann Emerg Mar 31;56(1):6-16. doi: 10.5045/br.2021.2020083. Accessed 18
Med. 2003 Feb;41(2):257-270. PMID: 12548278 Apr 2022. PMID: 33627521.
Authors/Task Force Members: Konstantinides SV, Meyer G, et Hostler DC, Marx ES, Moores LK, Petteys SK, Hostler JM,
al. 2019 ESC Guidelines for the diagnosis and management of Mitchell JD, Holley PR, Collen JF, Foster BE, Holley AB.
acute pulmonary embolism developed in collaboration with Validation of the International Medical Prevention Registry on
the European Respiratory Society (ERS): The Task Force for Venous Thromboembolism Bleeding Risk Score. Chest. 2016
the diagnosis and management of acute pulmonary embolism Feb;149(2):372-379. doi: 10.1378/chest.14-2842. Accessed 31
of the European Society of Cardiology (ESC). Eur Respir J. Mar 2017. PMID: 26867833.
2019 Aug 31. pii: 1901647. doi: 10.1183/13993003.01647-2019.
Hull RD, Lip GYH. Venous thromboembolism: anticoagulation
Accessed 10 Sep 2019. PMID: 31473594.
after initial management. UpToDate. https://www.uptodate.
Barbeau D. N. Deep venous thrombosis & pulmonary embolism. com. 04 Aug 2017. Accessed 31 Aug 2017.
http://wwwnc.cdc.gov.
Iles S, Beckert L, Than M, et al. Making a diagnosis of pulmonary
Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT: embolism - new methods and clinical issues. N Z Med J. 2003
Antithrombotic Therapy and Prevention of Thrombosis, 9th Jul;116(1177):U499. PMID: 12861313
ed: American College of Chest Physicians Evidence-Based
Institute for Clinical Systems Improvement. Health care
Clinical Practice Guidelines. Chest. 2012 Feb;141(Suppl
guideline: venous thromboembolism diagnosis and treatment.
2):e351S-e418S. doi:10.1378/chest.11-2299. PMID: 22315267.
12th ed. https://www.icsi.org. Jan 2012.
Bauer KA, Lip GYH. Overview of the causes of venous
Jaff MR, McMurtry MS, Archer SL, et al; American Heart
thrombosis. UpToDate. https://www.uptodate.com. Sep 2016.
Association Council on Cardiopulmonary, Critical Care,
Accessed 31 Mar 2017.
Perioperative and Resuscitation; American Heart Association
Becattini C, Agnelli G. Treatment of venous thromboembolism Council on Peripheral Vascular Disease; American Heart
with new anticoagulant agents. J Am Coll Cardiol. 2016 Association Council on Arterio. Management of massive
Apr 26;67(16):1941-1955. doi: 10.1016/j.jacc.2016.01.072. and submassive pulmonary embolism, iliofemoral deep
Accessed 31 Aug 2017. PMID: 27102510. vein thrombosis, and chronic thromboembolic pulmonary
Benrashid E, Youngwirth LM, Turley RS, Mureebe L. Venous hypertension: a scientific statement from the American Heart
thromboembolism: prevention, diagnosis and treatment. In: Association. Circulation. 2011 Apr;123(16):1788-1830. doi:
Cameron JL. Current Surgical Therapy. 12th ed. Philadelphia, 10.1161/CIR.0b013e318214914f. PMID: 21422387.
Pennylvania, USA:Elsevier, Inc;2017:1091-1098. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy
British Thoracic Society Standards of Care Committee for VTE disease: Antithrombotic Therapy and Prevention of
Pulmonary Embolism Guideline Development Group. British Thrombosis, 9th ed: American College of Chest Physicians
286
Evidence-Based Clinical Practice Guidelines. Chest. 2012 Scottish Intercollegiate Guidelines Network. Prevention and
Feb;141(2 Suppl):e419S-e494S. doi: 10.1378/chest.11-2301. management of venous thromboembolism: a national clinical
PMID: 22315268. guideline. SIGN. http://www.sign.ac.uk. Dec 2010.
Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy Shlensky JA, Thurber KM, O’Meara JG, et al. Unfractionated
for VTE disease: antithrombotic therapy and prevention heparin infusion for treatment of venous thromboembolism
of thrombosis, 9th edition: American College of Chest based on actual body weight without dose capping. Vasc
Physicians evidence-based clinical practice guidelines. Chest. Med. 2020 Feb;25(1):47-54. doi: 10.1177/1358863X19875813.
2012; 141:419-494. Accessed 13 May 2022. PMID: 31623539.
Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy Siskin GP, Kwan B. Inferior vena cava filters. eMedicine. http://
for VTE disease: CHEST Guideline and Expert Panel www.emedicine.com. Dec 2005.
Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j. Snow V, Qaseem A, Barry P, et al. Management of venous
chest.2015.11.026. PMID: 26867832. thromboembolism: a clinical practice guideline from the
Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for American College of Physicians and the American Academy
venous thromboembolic disease: American College of Chest of Family Physicians. Ann Intern Med. 2007 Feb;146(3):204-
Physicians Evidence-Based Clinical Practice Guidelines (8th 210. PMID: 17261857.
Edition). Chest. 2008 Jun;133(6 Suppl):454S-545S. PMID: Stein PD, Woodard PK, Hull RD, et al. Gadolinium-enhanced
18574272. magnetic resonance angiography for detection of acute
Kearon C. Diagnosis of pulmonary embolism. CMAJ. 2003 pulmonary embolism. Chest. 2003 Dec;124(6):2324-2328.
REFERENCES
Jan;168(2):183-194. PMID: 12538548. PMID: 14665516.
Landaw SA, Bauer KA. Approach to the diagnosis and therapy Tapson VF. Thrombolytic therapy in venous thromboembolism.
of lower extremity deep vein thrombosis. UpToDate. https:// UpToDate. https://www.uptodate.com.
www.uptodate.com. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the
Liew NC, Chang YH, Choi G,et al; Asian Venous Thrombosis diagnosis and management of acute pulmonary embolism:
Forum. Asian venous thromboembolism guidelines: the Task Force for the Diagnosis and Management of Acute
prevention of venous thromboembolism. Int Angiol. 2012 Pulmonary Embolism of the European Society of Cardiology
Dec;31(6):501-516. Accessed 31 Mar 2017. PMID: 23222928. (ESC). Eur Heart J. 2008 Sep;29(18):2276-2315. doi: 10.1093/
Lim W, Le Gal G, Bates SM, et al. American Society of eurheartj/ehn310. PMID: 18757870.
Hematology 2018 guidelines for management of venous Tovey C, Wyatt S. Diagnosis, investigation, and management of
thromboembolism: diagnosis of venous thromboembolism. deep vein thrombosis. BMJ. 2003 May;326(7400):1180-1184.
Blood Adv. 2018 Nov 27;2(22):3226-3256. doi: 10.1182/ PMID: 12775619.
bloodadvances.2018024828. Accessed 03 Sep 2019. PMID: Tran HA, Gibbs H, Merriman E, et al. New guidelines from
30482764. the Thrombosis and Haemostasis Society of Australia and
Ministry of Health Malaysia, National Heart Association of New Zealand for the diagnosis and management of venous
Malaysia, Academy of Medicine Malaysia. Clinical practice thromboembolism. Med J Aust. 2019 Mar;210(5):227-235.
guidelines: Management of Venous Thromboembolism. doi: 10.5694/mja2.50004. Accessed 03 Sep 2019. PMID:
Ministry of Health Malaysia. http://www.moh.gov.my. Jul 30739331.
2003. Verma B, Singh AK. Use of reteplase for thrombolysis in
Ministry of Health Malaysia. Clinical Practice Guidelines: patients with massive pulmonary embolism diagnosed by
Prevention and treatment of venous thromboembolism. bedside transthoracic echocardiography: a retrospective
Ministry of Health Malaysia. http://www.moh.gov.my/. Aug study of safety and efficacy. J Family Med Prim Care. 2019
2013. Accessed 31 Mar 2017. Oct 31;8(10):3155-3159. doi: 10.4103/jfmpc.jfmpc_512_19.
Ministry of Health Singapore. Venous thromboembolism. Accessed 13 May 2022. PMID: 31742135.
Treating with the right anticoagulant and duration. Agency Wang KL, Yap ES, Goto S, et al. The diagnosis and treatment
for Care Effectiveness. http://www.ace-hta.gov.sg. 28 May of venous thromboembolism in Asian patients. Thromb J.
2018. Accessed 10 Jan 2019. 2018;16(4). doi: 10.1186/s12959-017-0155-z. Accessed 24
National Institute for Health and Care Excellence (NICE). May 2018. PMID: 29375274.
Venous thromboembolic diseases: diagnosis, management Wilbur J, Shian B. Deep Venous Thrombosis and Pulmonary
and thrombophilia testing. NICE. https://www.nice.org.uk/. Embolism: Current Therapy. Am Fam Physician. 2017 Mar
26 Mar 2020. Accessed 03 Aug 2020. 1;95(5):295-302. http://www.aafp.org. Accessed 31 Mar 2017.
Ortel TL, Neumann I, Ageno W, et al. American Society of PMID: 28290648.
Hematology 2020 guidelines for management of venous
thromboembolism: treatment of deep vein thrombosis and
pulmonary embolism. Blood Adv. 2020 Oct 13;4(19):4693-
4738. doi: 10.1182/bloodadvances.2020001830. Accessed 18 Venous Thromboembolism - Prevention
Apr 2022. PMID: 33007077. American Academy of Orthopaedic Surgeons. Preventing
Qa s e em A , Chou R , Humphre y L L , e t al. Venous venous thromboembolic disease in patients undergoing
thromboembolism prophylaxis in hospitalized patients: a elective hip and knee arthroplasty. Evidence-based guideline
clinical practice guideline from the American College of and evidence report. American Academy of Orthopaedic
Physicians. Ann Intern Med. 2011 Nov;155(9):625-632. Surgeons. http://www.aaos.org. Sep 2011.
doi: 10.7326/0003-4819-155-9-201111010-00011. PMID: Anderson DR, Morgano GP, Bennett C, et al. American Society
22041951. of Hematology 2019 guidelines for management of venous
Quinlan D, McQuillan A, Eikelboom JW. Low-molecular-weight thromboembolism: prevention of venous thromboembolism
heparin compared with intravenous unfractionated heparin in surgical hospitalized patients. Blood Adv. 2019 Dec 10;
for treatment of pulmonary embolism: a meta-analysis 3(23): 3898–3944. doi: 10.1182/bloodadvances.2019000975.
of randomized, controlled trials. Ann Intern Med. 2004 Accessed 03 Aug 2020. PMID: 31794602.
Feb;140(3):175-183. PMID: 14757615. Australian Commission on Safety and Quality in Health Care
Ramzi DW, Leeper KV. DVT and pulmonary embolism: part (ACSQHC). Venous thromboembolism prevention clinical
I. Diagnosis. Am Fam Physician. 2004 Jun;69(12):2829-2836. care standard. ACSQHC. https://www.safetyandquality.gov.
PMID: 15222648. au. Oct 2018. Accessed 10 Oct 2019.
Ramzi DW, Leeper KV. DVT and pulmonary embolism: part Australian Government. National Health and Medical Research
II. Treatment and prevention. Am Fam Physician. 2004 Council. Clinical practice guideline for the prevention
Jun;69(12):2841-2848. PMID: 15222649. of venous thromboembolism (deep vein thrombosis and
Riedel M. Acute pulmonary embolism 1: pathophysiology, pulmonary embolism) in patients admitted to Australian
clinical presentation, and diagnosis. Heart. 2001 Feb;85(2):229- hospital. Draft for public consultation. National Health and
240. PMID: 11156681. Medical Research Council. http://www.nhmrc.gov.au. 2009.
287
Bauer KA, Lip GYH. Overview of the causes of venous Ministry of Health Malaysia. Clinical Practice Guidelines:
thrombosis. UpToDate. https://www.uptodate.com. Sep 2016. Prevention and treatment of venous thromboembolism.
Accessed 31 Mar 2017. Ministry of Health Malaysia. http://www.moh.gov.my/. Aug
Bauer KA. Risk and prevention of venous thromboembolism 2013. Accessed 31 Mar 2017.
in adults with cancer. UpToDate. https://www.uptodate. National Clinical Guideline Centre - Acute and Chronic
com. 25 May 2016. Conditions. Venous thromboembolism: reducing the risk
Benrashid E, Youngwirth LM, Turley RS, Mureebe L. Venous of venous thromboembolism (deep vein thrombosis and
thromboembolism: prevention, diagnosis and treatment. In: pulmonary embolism in patients admitted to hospital).
Cameron JL. Current Surgical Therapy. 12th ed. Philadelphia, Methods, evidence & guidance. National Institute for Health
Pennylvania, USA:Elsevier, Inc;2017:1091-1098. and Care Excellence (NICE). https://www.nice.org.uk. 2010.
Czyrny JJ, Kaplan RE, Wilding GE, et al. Electrical foot National Collaborating Centre for Acute Care. Venous
stimulation: a potential new method of deep venous thromboembolism:reducing the risk of venous
thrombosis prophylaxis. Vascular. 2010 Jan;18(1):20-27. thromboembolism (deep vein thrombosis and pulmonary
PMID: 20122356. embolism) in inpatients undergoing surgery. Methods,
evidence & guidance. http://www.nice.org.uk. Apr 2007.
Dupras D, Bluhm J, Felty C, et al. Institute for Clinical
Systems Improvement (ICSI). Health care guideline: venous National Institute for Health and Clinical Excellence (NICE).
Rivaroxaban for the prevention of venous thromboembolism
thromboembolism diagnosis and treatment. 13th ed. ICSI.
after total hip or total knee replacement in adults. NICE.
https://www.icsi.org. Jan 2013. http://www.nice.org.uk/. Apr 2009.
REFERENCES
Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous Pai M, Douketis JD. Prevention of venous thromboembolic
thromboembolism: American College of Chest Physicians disease in acutely ill hospitalized medical adults. UpToDate.
Evidence-Based Clinical Practice Guidelines (8th Edition). https://www.uptodate.com. 04 Mar 2022. Accessed 21 Apr
Chest. 2008 Jun;133(6)(Suppl):381S-453S. doi: 10.1378/ 2022.
chest.08-0656. PMID: 18574271.
Qa s e em A , Chou R , Humphre y L L , e t al. Venous
Gross PL, Weitz JI. New anticoagulants for treatment of venous thromboembolism prophylaxis in hospitalized patients: a
thromboembolism. Arterioscler Thromb Vasc Biol. 2008 clinical practice guideline from the American College of
Mar;28(3):380-386. doi: 10.1161/ATVBAHA.108.162677. Physicians. Ann Intern Med. 2011 Nov;155(9):625-632.
PMID: 18296593. doi: 10.7326/0003-4819-155-9-201111010-00011. PMID:
Heidbuchel H, Verhamme P, Alings M, et al. Updated European 22041951.
Heart Rhythm Association Practical Guide on the use of Roderick P, Ferris G, Wilson K, et al. Towards evidence-based
non-vitamin K antagonist anticoagulants in patients with non- guidelines for the prevention of venous thromboembolism:
valvular atrial fibrillation. Europace. 2015 Oct;17(10):1467- s ystematic re v ie ws of me chanical metho ds , oral
1507. doi: 10.1093/europace/euv309. PMID: 26324838. anticoagulation, dextran and regional anaesthesia as
Henke PK, Kahn SR, Pannucci CJ, et al. Call to action to thromboprophylaxis . Health Technol Assess . 2005
prevent venous thromboembolism in hospitalized patients: Dec;9(49):iii-iv, ix-x, 1-78. PMID: 16336844.
a policy statement from the American Heart Association. Schünemann HJ, Cushman M, Burnett AE, et al. American
Circulation. 2020 Jun 16;141(24):e914-e931. doi: 10.1161/ Society of Hematology 2018 guidelines for management
CIR.0000000000000769. Accessed 21 Apr 2022. PMID: of venous thromboembolism: prophylaxis for hospitalized
32375490. and nonhospitalized medical patients. Blood Adv. 2018 Nov
Hirsh J. Advances and contemporary issues in prophylaxis for 27;2(22):3198-3225. doi: 10.1182/bloodadvances.2018022954.
deep vein thrombosis. Chest. 2003 Dec;124(6):S347-S348. Accessed 10 Oct 2019. PMID: 30482763.
Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: Scottish Intercollegiate Guidelines Network (SIGN). Prevention
American College of Chest Physicians Evidence-Based and management of venous thromboembolism. A national
Clinical Practice Guidelines (8th Edition). Chest. 2008 clinical guideline. SIGN. http://www.sign.ac.uk. Dec 2010.
Jun;133 (6 Suppl):141S-159S. doi: 10.1378/chest.08-0689. The Australian and New Zealand Working Party on the
PMID: 18574264. Management and Prevention of Venous Thromboembolism.
Prevention of venous thromboembolism: best practice guideline
Institute for Clinical Systems Improvement (ICSI). Venous for Australia & New Zealand. 4th ed. http://www.surgeons.
thromboembolism prophylaxis. 8th ed. ICSI. https://www. org. 2007.
icsi.org.
Valentine KA, Hull RD. Therapeutic use of heparin and low
Jobin S, Kalliainen L, Adebayo L, et al. Institute for Clinical molecular weight heparin. UpToDate. https://www.uptodate.
Systems Improvement . Venous thromboembolism com. Dec 2011.
prophylaxis. Institute for Clinical Systems Improvement.
Wang KL, Yap ES, Goto S, et al. The diagnosis and treatment
https://www.icsi.org. Nov 2012.
of venous thromboembolism in Asian patients. Thromb J.
Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy 2018;16(4). doi: 10.1186/s12959-017-0155-z. Accessed 24
for VTE disease: Antithrombotic Therapy and Prevention of May 2018. PMID: 29375274.
Thrombosis, 9th ed: American College of Chest Physicians Wilbur J, Shian B. Deep Venous Thrombosis and Pulmonary
Evidence-Based Clinical Practice Guidelines. Chest. 2012 Embolism: Current Therapy. Am Fam Physician. 2017 Mar
Feb;141(2)(Suppl):e419S-e494S. doi: 10.1378/chest.11-2301. 1;95(5):295-302. http://www.aafp.org. Accessed 31 Mar 2017.
PMID: 22315268. PMID: 28290648.
Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy Weitz JI, Hirsh J, Samama MM. New antithrombotic drugs:
for VTE disease: CHEST Guideline and Expert Panel American College of Chest Physicians Evidence-Based Clinical
Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j. Practice Guidelines (8th Edition). Chest. 2008 Jun;133 (6
chest.2015.11.026. PMID: 26867832. Suppl):234S-256S. doi: 10.1378/chest.08-0673. PMID: 18574267.
Kearon C. Duration of venous thromboembolism prophylaxis Zalpour A, Oo TH. Update on edoxaban for the prevention and
after surgery. Chest. 2003 Dec;124(6 Suppl):386S-392S. treatment of thromboembolism: clinical applications based
PMID: 14668422. on current evidence. Adv Hematol. 2015;2015:920361. doi:
Liew NC, Chang YH, Choi G,et al; Asian Venous Thrombosis 10.1155/2015/920361. PMID: 26351456.
Forum. Asian venous thromboembolism guidelines:
prevention of venous thromboembolism. Int Angiol. 2012
Dec;31(6):501-516. Accessed 31 Mar 2017. PMID: 23222928.
Ministry of Health, Academy of Medicine Malaysia, College
of Surgeons Malaysia. Consensus on prophylaxis of venous
thromboembolism. Academy of Medicine Malaysia. http://
www.acadmed.org.my. Jun 2000.
288
Bookmark
Front Back

Cardiology Guide

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cardiology Guide

Uploaded by

Copyright:

Available Formats

9WhZ_ebe]o=k_Z[

Publisher of CIMS/IDR Chief Executive Officer - MIMS Group

CIMS Cardiology Guide provides detailed prescribing information covering

Pre-hospital & Emergency Department management includes:

PATIENTS WITH CONFIRMED UA/NSTEMI

A Continue antiplatelet therapy A Continue anti-

LONG-TERM (OUTPATIENT) TREATMENT

1 ISCHEMIC-TYPE CHEST DISCOMFORT OR ANGINAL EQUIVALENT

Acute Coronary Syndrome (ACS)

ECG taken without symptoms

5 EVALUATION FOR RISK STRATIFICATION

5 EVALUATION FOR RISK STRATIFICATION (CONT’D)

7 INVASIVE STRATEGIES (CONT'D)

A PHARMACOLOGICAL THERAPY (CONT’D)

A PHARMACOLOGICAL THERAPY (CONT’D)

• A protease activated receptor-1 (PAR-1) antagonist that inhibits platelet activation

A PHARMACOLOGICAL THERAPY (CONT’D)

A PHARMACOLOGICAL THERAPY (CONT’D)

A PHARMACOLOGICAL THERAPY (CONT’D)

C PATIENT & CAREGIVER EDUCATION

C PATIENT & CAREGIVER EDUCATION (CONT'D)

D RISK FACTOR MANAGEMENT

D RISK FACTOR MANAGEMENT (CONT’D)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

ANTIPLATELET AGENTS (CONT’D)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

BETA-BLOCKERS (ORAL) (CONT’D)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

DIRECT THROMBIN INHIBITORS

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

GLYCOPROTEIN IIB/IIIA INHIBITORS (CONT’D)

LOW-MOLECULAR-WEIGHT HEPARINS (LMWH)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

NITRATES (ORAL - LONG-ACTING)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

NITRATES (TOPICAL - LONG-ACTING)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

UNFRACTIONATED HEPARIN (UFH)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

HIGH-VERY HIGH RISK

1 EVALUATION ON ROUTINE PHYSICIAN VISIT

1 EVALUATION ON ROUTINE PHYSICIAN VISIT (CONT’D)

2 RISK STRATIFICATION (CONT’D)

CVD RISK CATEGORIES

some increase in continuous imaging

B LIFESTYLE MODIFICATION (CONT’D)

C MANAGEMENT OF OTHER RISK FACTORS

C MANAGEMENT OF OTHER RISK FACTORS (CONT’D)

of a sodium-glucose co-transporter 2 inhibitor (SGLT2) or a glucagon-like peptide-1 (GLP-1) receptor agonist,

D PHARMACOLOGICAL THERAPY (CONT’D)

D PHARMACOLOGICAL THERAPY (CONT’D)

ANTICOAGULANTS, ANTIPLATELETS & FIBRINOLYTICS (THROMBOLYTICS)

All dosage recommendations are for non-pregnant & non-breastfeeding women,

ANTICOAGULANTS, ANTIPLATELETS & FIBRINOLYTICS (THROMBOLYTICS) (CONT’D)

hemorrhage history, known allergy, or severe hepatic impairment

All dosage recommendations are for non-pregnant & non-breastfeeding women,

All dosage recommendations are for non-pregnant & non-breastfeeding women,

9WhZ_ebe]o=k_Z[

• 50-69 years: <5%