CPG Ua-Nstemi PDF

June 2011 MOH/P/PAK/219.
11(GU)
Clinical Practice Guidelines on
management of Unstable Angina/Non ST
Elevation Myocardial Infarction (UA/NSTEMI) 2011
STATEMENT OF INTENT
This guideline was developed to be a guide for best clinical practice

in the management of Unstable Angina/ Non ST Elevation Myocardial
Infarction (UA/NSTEMI). It is based on the best available evidence at the
time of development. Adherence to this guideline does not necessarily
lead to the best clinical outcome in individual patient care. Thus, every
health care provider is responsible for the management of his/her
unique patient, based on the clinical presentation and management
options available locally.
REVIEW OF THE GUIDELINE
This guideline was issued in 2011 and will be reviewed in 2016 or earlier
if important new evidence becomes available.
CPG Secretariat
Health Technology Assessment Unit
Medical Development Division
Level 4, Block EI, Parcel E
Government Offices Complex
62590 Putrajaya, Malaysia
Available on the following websites:
http://www.malaysianheart.org
http://www.moh.gov.my
http://www.acadmed.org.my
1
SUMMARY
1. Acute coronary syndrome is a spectrum of UA/NSTEMI and STEMI.
The clinical presentation will depend on the acuteness and severity
of coronary occlusion.
2. The diagnosis of UA/NSTEMI is based on history ± dynamic

ECG changes (without persistent ST elevation), ± raised cardiac
biomarkers.
3. In UA cardiac biomarkers are normal while in NSTEMI it is elevated.
4. Risk stratification is important for prognosis and to guide management

(Flowchart 1, pg 3).
5. Initial management of intermediate/high risk patients includes optimal

medical therapy with aspirin I,A and clopidogrel I,A (or ticagelor I,B),
UFH I,A or LMWH I,A or fondaprinux I,A. Prasugrel may be considered
as an alternative to clopidogrel in high risk patients after coronary
angiography if PCI is planned I,B. (Table 1, pg 4)
6. Patients with refractory angina and/or hemodynamically unstable

should be considered for urgent coronary angiography and
revascularization I,C.
7. Intermediate/high risk patients should be considered for early invasive

strategy (<72 hours). If admitted to a non-PCI centre, they should be
considered for transfer to a PCI centre I,A.
8. Low risk patients should be assessed non-invasively for ischemia I,A.

(Fig 1, pg 5)
9. All patients should receive optimal medical therapy at discharge.

This includes aspirin I,A, clopidogrel I,B (or ticagrelor I,B or prasugrel I,B if
given during PCI), ß-blockers I,B, ACE-I I,A or ARB (if ACE-I intolerant
I,B
) and statins I,A. If recurrent or residual ischemia is present, then
anti anginal therapy should also be given I,C. These include nitrates
I,C
, calcium channel blockers IIa, C and/or metabolic agents IIa, C (Table
1, pg 4)
10. These drugs should be uptitrated as outpatient to the recommended

tolerated doses I,C.
11. Cardiac rehabilitation and secondary prevention programs

which includes lifestyle modification is an integral component of
management I,A.
2
Flowchart 1: Risk Stratification of UA/NSTEMI

Flowchart 1: Risk Stratification of UA/NSTEMI
Low risk Intermediate/High Risk

no angina in the past Patients with recurrent chest pain
no ongoing angina Early post infarction unstable angina
no prior use of Dynamic ST-segment changes
antianginal therapy Elevated cardiac biomarkers
normal ECG Diabetes
normal cardiac Hemodynamic instability
biomarkers Depressed LV function (LVEF <40%)
normal LV function Major arrhythmias (VF, VT)
younger age group
This includes (see Table 1, pg:4):

Aspirin
Clopidogrel or ticagrelor (or prasugrel after
coronary angiography)
Antithrombotics (UFH or LMWH or
Fondaparinux)
β-blockers
Statins
ACE-I/ARB
Nitrates
+ CCB (if β-blockers contraindicated and/or
unresponsive to above)
+ GP IIb/IIIa inhibitor
 Medical therapy* Coronary Angiography and Revascularization*

* This includes aspirin + β-
blockers + GTN *If patient is admitted to a non-PCI centre and has
ongoing ischaemia despite optimal medical therapy, it is
 Risk stratify as recommended to transfer the patient for coronary
outpatient (Fig1, pg 5) angiography with view to revascularization.
CCB : Calcium channel blockers

UFH : Unfractionated heparin
LMWH : Low Molecular Weight Heparin
GP : Glycoprotein
VF: Ventricular fibrillation
VT: Ventricular tachycardia
3
Table 1: Medications in Intermediate / High Risk Patients with UA/NSTEMI

Table 1: Medications in Intermediate / High Risk Patients with UA/NSTEMI
Drug Initial and In- Medication Comments

hospital at discharge
medication
Aspirin I,A I,A Continued long term if tolerating
+ Clopidogrel I,A I,A Used in addition to aspirin as part of dual
antiplatelet therapy.
I,B To be continued at least 1 month and
ideally for at least a year post
UA/NSTEMI and,
I,C 6-12months or longer post DES
implantation
or, Ticlopidine IIa,B IIa,B Used in addition to aspirin as part of dual
antiplatelet therapy. This is a less
preferred alternative to clopidogrel.
or, prasugrel I,B I,B Used in addition to aspirin as part of dual
antiplatelet therapy. Alternative to
clopidogrel in high risk patients
undergoing PCI.
or, ticagrelor I,B I,B Used in addition to aspirin as part of dual
antiplatelet therapy. Alternative to
clopidogrel.
+ UFH I,A - Given for 2-8 days
or, LMWH I,A - Given for 2-8 days
I,A - Used in patients treated conservatively.
or, fondaprinux
Given for 8 days or duration of
hospitalization
or, Bivalirudin I,A Used as an alternative to UFH and
GPIIb/IIIa inhibitors during PCI
+ β-blockers 1,B I,B Should be administered early if no
contraindications and continued
indefinitely if ischemia is present.
I,A Continued indefinitely in the presence of
LV dysfunction (LVEF<40%)
+ ACE-I I,A I,A Should be administered early in patients
with LV dysfunction (LVEF< 40%), heart
failure, diabetes, hypertension or CKD.
IIa, A Should be considered long term to
prevent recurrent ischemia
I,B I,B As an alternative to ACE-I in intolerant
or ARB patients
+ Statins I, A I,A High potency statins should be used
early till target LDL-C levels are achieved
and continued indefinitely.
+/- calcium 1,B I,B If intolerant to β-blockers
channel blockers IIa,C IIa,C Indicated for residual/ recurrent ischemia.
+/- nitrates I,C I,C Indicated for residual/ recurrent ischemia.
4
Figure 1: Non-invasive investigation of Low Risk Patients with
UA/NSTEMI*
Figure 1: Non-invasive investigation of Low Risk Patients with UA/
NSTEMI*
Low Risk patients with UA/NSTEMI
Normal ECG, Abnormal ECG,

Good Exercise Tolerance Limited exercise tolerance
Exercise/Dobutamine Stress
Exercise stress test Equivocal
Echocardiogram or
Radionuclear Perfusion
Scan
Negative test Positive Equivocal / Positive Test
Risk Factor Reduction +

Medical Therapy for Coronary Angiogram
CAD
* Low risk patients have :
no angina in the past

no ongoing angina
no prior use of antianginal therapy
normal ECG
normal cardiac biomarkers
younger age group
normal LV function
Patients who have undergone revascularization and with residual/recurrent or a

change in symptoms should be investigated as above.
All Intermediate/High Risk UA/NSTEMI patients should be considered for coronary

angiography and revascularization. (Flowchart 1, pg 3)
5
MESSAGE FROM THE DIRECTOR GENERAL OF HEALTH
In the last 8 years since the last CPG UA/NSTEMI was published, the
management of this most important of prodrome to a full blown STEMI has
changed significantly. However, like in 2002, despite the World Health Statistics
(2010) reporting a healthy rise in the number of doctors per population, Health
Facts 2008 from the Ministry of Health Malaysia still state that the main cause
of death in the country is cardiovascular disease.
It is now recognized that early, aggressive management of UA/NSTEMI can

improve clinical outcomes both in the short- and long-term. Mounting evidence
in the early use of antithrombotic agents, early access to revascularization,
and secondary prevention strategies, contribute to the significant reduction of
cardiovascular mortality and morbidity.
In the last few years, the establishment of the National Cardiovascular Database,
comprising of the Acute Coronary Syndrome (NCVD-ACS), Percutaneous
Coronary Intervention (NCVD-PCI), as well as the Malaysian Cardiac Surgery
Registry (MyCARE), has now provided us a unified tool to capture important
data on cardiovascular disease presentation and management in our country.
We now know that the incidence of ACS in Malaysia is approximately 141 per
100,000 population per year, and the inpatient mortality rate is approximately
7%, comparable to many developed countries. We have recorded over 8000
PCI performed in Malaysia over the last 3 years, with a very low rate of serious
complications, particularly in elective procedures (<1%).
Further, in the last few years, increasing numbers of Cardiology Units, as well as
well-run General Medicine Units, are participating in Phase I to III clinical trials.
More Malaysians are now being offered the opportunity to be directly involved
in new therapies and are also being provided stringent world-class care in the
context of a clinical trial setting.
In this rapidly evolving landscape of UA/STEMI management, and a definite

increase in patient load in the face of the rising prevalence of cardiovascular risk
factors published in the recent National Health and Morbidity Survey III, it is time
now to update this CPG UA/NSTEMI. We believe this will provide healthcare
providers with strategies, derived from contemporary evidence, to improve the
diagnosis and treatment of this unpredictable condition.
Dato Hasan Abdul Rahman,

Director General of Health,
Ministry of Health, Malaysia
6
FOREWARD FROM THE AMERICAN COLEGE OF CARDIOLOGY
On behalf of the American College of Cardiology I want to offer my hearty

congratulations to the National Heart Association of Malaysia in their creation
of this ACS NSTEMI clinical practice guideline update. Adherence to evidence
based medicine has conclusively been shown to improve clinical outcomes.
The field of cardiology in particular has been relatively blessed with a plethora
of many superb international randomized clinical trials (RCT) that form the
backbone of our cardiovascular clinical practice guidelines. The translation
and application of the RCT-generated evidence base to the Malaysian
“bedside” is the mission of clinical practice guidelines. In particular, NHAM’s
Class 1 recommendations for the management of ACS/NSTEMIs represent
the “must do’s” in the management of acute coronary syndromes as these care
measures directly lead to decrease in mortality and morbidity in cardiovascular
disease. In the United States over the past few decades a marked decrease
in the cardiovascular mortality and morbidity has been achieved. This
admirable accomplishment is directly due to increased adherence in clinical
practice guidelines for secondary and primary prevention of coronary disease
along with application of evidence based strategies in the management of
acute coronary syndromes. NHAM’s clinical practice guideline reflects well
the local care environment here in Malaysia creating the potential of saving
thousands of lives though your promotion of evidence based ACS care. The
participation in a national acute coronary syndrome registry is an important
component of the cardiovascular quality cycle. If we don’t measure it, we can’t
manage it!! We applaud the leadership of the National Heart Association of
Malaysia with its enthusiasm and expertise manifested in NHAM’s updated
ACS clinical practice guidelines along with your vigorous promotion of the
NCVD Malaysian Acute Coronary Syndrome Registry. The ACC looks forward
in future cardiovascular collaborations with the National Heart Association
of Malaysia in the areas of cardiovascular science, education and in the
promotion of cardiovascular quality.
Congratulations and a personal toast to Malaysian heart health!
Ralph Brindis, MD, MPH, FACC, FSCAI
Immediate Past President,

American College of Cardiology
7
Members of the Expert Panel

Members ofMembers
the Expert
of Panel
the Expert Panel
erson:
Chairperson:
amalar
Dr.Rajadurai
Jeyamalar Rajadurai Consultant Cardiologist,
Consultant Cardiologist,
Sime DarbySime
Medical
Darby
Center
Medical Center
Subang Jaya,
Subang
Selangor
Jaya, Selangor
Members
ers (in
Members
(inalphabetical
(in alphabetical
alphabeticalorder)
order) order)
mad Nizar
Dr. Ahmad Nizar Consultant Cardiologist,
Sime DarbySime
Medical
Darby
Center
Medical Center
Subang Jaya,Selangor
Subang Jaya,Selangor
uar Rapaee
Dr. Anuar Rapaee Consultant Cardiologist,
Hospital Serdang
Hospital Serdang
Chandran
Dr. Aris Chandran Consultant Physician,
Consultant Physician,
Hospital Sultanah
Hospital
Bainun,
Sultanah
IpohBainun, Ipoh
ar Ismail
Dr. Omar Ismail Consultant Cardiologist,
Hospital Besar
Hospital
PulauBesar
Pinang
Pulau Pinang
h Maskon
Dr. Oteh Maskon Consultant Cardiologist
Consultant Cardiologist
Hospital UKM,
Hospital
KualaUKM,
Lumpur
Kuala Lumpur
e Raman
Dr. Sree Raman Consultant Physician,
Consultant Physician,
Hospital Tuanku
Hospital
Jaafar,
Tuanku
Seremban
Jaafar, Seremb
(HTA trained)
(HTA trained)
Kui Dr.
HianSim Kui Hian Consultant Cardiologist,
Sarawak General
Sarawak
Hospital,Kuching
General Hospital,Kuchi
n Azman
Dr. Wan Azman Consultant Cardiologist,
University Malaya
University
Medical
Malaya
Center
Medical Cente
bayaah
Dr.Zambahari
Robayaah Zambahari Consultant Cardiologist,
Institute Jantung
Institute
Negara,
Jantung Negara,
Kuala Lumpur Kuala Lumpur
8
External Reviewers (in alphabetical order):

External Reviewers (in alphabetical
External Reviewers (in alphabetical
order): order):
Dr. Chan Hiang

Dr. Chan
Chuan
Hiang Chuan ConsultantConsultant
Physician Physician
Sarawak General
SarawakHospital,Kuching
General Hospital,Ku
Dr. Jeyaindran
Dr. Jeyaindran
SinnaduraiSinnadurai ConsultantConsultant
Physician Physician
Head of Internal
Head of Medicine,
Internal Medicine,
Ministry OfMinistry
Health, Of Health,
Hospital Kuala
Hospital
Lumpur
Kuala Lumpur
Dr. Lee Chuey

Dr. Lee
YanChuey Yan ConsultantConsultant
Cardiologist
Cardiologist
Hospital Sultanah
HospitalAminah
Sultanah
Johor
Aminah Joh
Dr. Lee Fatt

Dr.Soon
Lee Fatt Soon ConsultantConsultant
Geriatrician
Geriatrician
Hospital Kuala
Hospital
Lumpur,
KualaKL
Lumpur, KL
Dr. Kim Tan

Dr. Kim Tan ConsultantConsultant
Cardiologist,
Cardiologist,
Sunway Medical
Sunway Center,
Medical Center,
Sunway,Selangor
Sunway,Selangor
Dr. V Paranthaman
Dr. V Paranthaman Family Medicine
FamilySpecialist,
Medicine Specialist,
Klinik Kesihatan
Klinik Kesihatan
Jelapang, Jelapang,
Ipoh, PerakIpoh, Perak
Dr. SanthaDr.
Kumari
Santha Kumari ConsultantConsultant
Physician Physician
Hospital Sultanah
HospitalRahimah
SultanahKelang
Rahimah K
Dr. Tee Lian

Dr.Kim
Tee Lian Kim General Practitioner,
General Practitioner,
Klinik Young,
Klinik
Newton
Young,
and
Newton
Partners
and Par
Kuala Lumpur/Petaling
Kuala Lumpur/Petaling
Jaya Jaya
Dr. Wong Kai

Dr. Wong
Fatt Kai Fatt General Practitioner,
General Practitioner,
LW MedicalLWAssociates
Medical Associates
Kuala Lumpur
Kuala Lumpur
Dr. Zurkarnai
Dr. Yusof
Zurkarnai Yusof ConsultantConsultant
Cardiologist
Cardiologist
Hospital Universiti
Hospital Sains
Universiti
Malaysia
Sains Malay
Kota Baru,Kota
Kelantan
Baru, Kelantan
9
RATIONALE AND PROCESS OF GUIDELINE DEVELOPMENT
Rationale:
Coronary artery disease (CAD) is an important cause of morbidity and

mortality in Malaysia. Patients with CAD may present as stable angina or
as acute coronary syndromes (ACS). ACS is a spectrum of disease
ranging from unstable angina (UA), non ST elevation myocardial infarction
(NSTEMI) to ST elevation myocardial infarction depending on the
acuteness and severity of the coronary occlusion. The last CPG on
UA/NSTEMI was published in 2002. Thus the need for an update.
Objectives:
The objectives of this guideline are to:

provide guidance on the most effective evidence based therapeutic
strategies in patients with UA/NSTEMI to reduce in-hospital
morbidity and mortality.
reduce the risk of recurrent cardiac events in these patients
This Clinical Practice Guideline (CPG) has been drawn up by a committee

appointed by the National Heart Association of Malaysia, Ministry of
Health and the Academy of Medicine. It comprises cardiologists and
general physicians from the government and private sectors as well as
from the Universities.
Process:
Evidence was obtained by systematic review of current medical literature

on UA/NSTEMI using the usual search engines – PubMed, Medscape and
Ovid. The other international guidelines (American and European) on the
subject were also studied. After much discussion, the draft was then
drawn up by the members of the Expert Panel and submitted to the
Technical Advisory Committee for Clinical Practice Guidelines, Ministry of
Health Malaysia and key health personnel in the major hospitals of the
Ministry Of Health and the Private Sector for review and feedback.
The clinical questions were divided into major subgroups and members of
the Expert Panel were assigned individual topics. The group members met
several times throughout the development of the guideline. All retrieved
literature were appraised by individual members and subsequently
presented for discussion during group meetings. All statements and
recommendations formulated were agreed collectively by members of the
Expert Panel. Where the evidence was insufficient the recommendations
were derived by consensus of the Panel. The draft was then sent to local
external reviewers for comments. It was also sent to the American College
of Cardiology and the European Society of Cardiology for feedback.
10
10
The level of recommendation and the grading of evidence used in this

guideline was adapted from the American Heart Association and the
European Society of Cardiology (ACC/ESC) and outlined on page 13. In
the text, this is written in black on the left hand margin. In the Summary
and Key Recommendations, it is written as a superscript immediately after
the therapeutic agent or at the end of the statement as applicable.
Clinical Questions Addressed:
What is the current evidence on the best practice strategies to

reduce morbidity and mortality in patients with UA/NSTEMI?
Which of these strategies are applicable to our local setting
considering our limited health resources?
Target Group:
This guideline is directed at healthcare providers including general

practitioners, medical officers, general and family physicians and
cardiologists.
Target Population:
All patients (older than 18 years) presenting with chest pain.
Period of Validity of the Guidelines:
This guideline needs to be revised at least every 5 years to keep abreast

with recent developments and knowledge.
Applicability of the Guidelines:
This guideline was developed taking into account our local health
resources. The following are available at all state and district government
hospitals with physicians.
ECG machines, measurement of cardiac biomarkers (including
troponins), treadmill stress ECG’s and echocardiograms.
Most of the medications that are recommended in this guideline are
already approved for use in Malaysia.
Intermediate/high risk patients should be identified early and
transferred to hospitals with existing catheterization facilities. In
accordance with the national health plan, the ministry has already
proposed the setting up of catheterization laboratories in most of
the state hospitals.
This guideline aims to streamline management of cardiac patients and

educate health care professional on strategies to optimize existing
resources. We do not anticipate barriers to its implementation.
11
11
Implementation of the Guidelines:
The implementation of the recommendations of a CPG is part of good

clinical governance. To ensure successful implementation of this CPG we
suggest:
increasing public awareness of CAD and its therapies.

continuing medical education and training of healthcare providers.
clinical audit – This is done by monitoring :
o In-hospital mortality and morbidity in patients admitted with
ACS (NCVD registry)
o Readmission rates for a cardiac related event in patients
discharged with a diagnosis of ACS. Elective admissions for
cardiac procedure are excluded.
o Documentation of the following;
- Risk stratification
- Discharge medications to include, antiplatelets,
statins, ACE-inhibitors and Beta blockers.
- Discharge plan with regards to cardiac
assessment/tertiary care referral.
12
12
GRADES OF RECOMMENDATIONS AND LEVELS OF EVIDENCE
GRADES OF RECOMMENDATION
Conditions for which there is evidence and/or general agreement

I that a given procedure/therapy is beneficial, useful and/or
effective.
Conditions for which there is conflicting evidence and/or
II divergence of opinion about the usefulness/efficacy of a
procedure/therapy.
II-a Weight of evidence/opinion is in favor of its usefulness/efficacy.
II-b Usefulness/efficacy is less well established by evidence/opinion
Conditions for which there is evidence and/or general agreement

III that a procedure/therapy is not useful /effective and in some
cases may be harmful.
LEVELS OF EVIDENCE
Data derived from multiple randomized clinical trials or meta

A
analyses
Data derived from a single randomized clinical trial or large non
B
randomized studies
Only consensus of opinions of experts, case studies or standard
C
of care
Adapted from the American Heart Association/American College of Cardiology

(AHA/ACC) and the European Society of Cardiology (ESC)
13
13
TABLE OF CONTENTS
Statement of Intent 1
Summary 2
Flowchart 1, Table 1, Figure 1 3-5
Message from Director General of Health, MOH 6
Foreward from President of American College of Cardiology 7
Members of the Expert Panel 8
External Reviewers 9
Rationale and Process of Guideline Development 10-13
1. Introduction 15
2. Definition of terms 15-16
3. Pathogenesis 16
4. Diagnosis 17-19
4.1 History 17
4.2 Physical Examination 17
4.3 Electrocardiography 18
4.4 Cardiac Biomarkers 18-19
4.5 Other Diagnostic Modalities 19
5. Risk Stratification 20-21
5.1 Assessment of Risk 20
5.2 Rationale for Risk Assessment 20
5.3 Risk Scores for Prognosis of UA/NSTEMI 20
5.4 Risk Assessment for Bleeding 21
6. Triage 21-22
7. Management of UA/NSTEMI 22-31
7.1 Pre hospital Management 23
7.2 In Hospital Management 23-31
7.2.1 Initial Management 23
7.2.2 Antiplatelet Agents 23-25
7.2.3 Anticoagulant Therapy 25-27
7.2.4 Anti Ischemic Drug Therapy 28-30
8. Revascularization strategies 31-32
8.1 Routine early invasive management 31
8.2 Routine early conservative management 32
9. UA/NSTEMI in special groups 32-36
9.1 UA/NSTEMI in Elderly 32-34
9.2 UA/NSTEMI in Women 34
9.3 UA/NSTEMI in Chronic Kidney Disease 35
9.4 UA/NSTEMI in diabetes 36
10. Post Hospital Discharge 36-40
10.1 Medications post discharge 36-39
10.2 Investigations during Follow Up 39-40
11. Cardiac Rehabilitation 40-41
12. References 42-50
13. Appendix 51-57
14. Acknowledgement 58
15. Disclosure Statements 58
16. Source of Funding 58
14
1. INTRODUCTION
Cardiovascular Disease (CVD) is one of the main causes of mortality and

morbidity in Malaysia. The estimated incidence of Acute Coronary
Syndrome (ACS) is 141 per 100,000 population per year, and the in-
patient mortality rate is approximately 7%. This data is derived from the
National Cardiovascular Disease Database (NCVD) based on the ACS
2006 Annual report1. These figures are similar to that of many developed
countries. Unstable Angina/Non ST Elevation Myocardial Infarction
(UA/NSTEMI) which falls within the spectrum of ACS, is an important
cause of cardiac morbidity and mortality.
The last CPG on UA/NSTEMI was published in 2002. Since then, there
have been significant advances in the management of this important
condition. Thus, it is timely to update this CPG to keep abreast with
contemporary evidenced based state of the art management of this
condition.
2. DEFINITION OF TERMS
ACS is a clinical spectrum of ischemic heart disease. Depending upon the

degree and acuteness of coronary occlusion, it can present as (Figure 2,
pg 16):
Unstable angina (UA)

Non-ST elevation myocardial infarction (NSTEMI)
ST elevation myocardial infarction (STEMI)
These changes may be dynamic. A patient presenting with UA may

progress to NSTEMI or even STEMI.
The terms Q-wave myocardial infarction (QwMI) and non-Q wave

myocardial infarction (NQMI) are no longer preferred.
Unstable angina may be classified as2 (Appendix I, pg 51):
I. New onset of severe angina or accelerated angina; no rest pain

II. Angina at rest within past month but not within preceding 48 hours
(angina at rest, subacute)
III. Angina at rest within 48 hours (angina at rest, acute)
It may be further classified according to clinical circumstances into either:
A) Secondary – develops in the presence of extracardiac disease

B) Primary – develops in the absence of extracardiac disease
C) Post-infarct – develops within 2 weeks of an acute MI
15
15
The diagnosis of NSTEMI

The diagnosis is established
of NSTEMI if a cardiac
is established biomarker
if a cardiac is detected.
biomarker is detected.
The diagnosis of NSTEMI is established if a cardiac biomarker is detected.
In NSTEMI, ST/TST/T
In NSTEMI, changes maymay
changes be present
be present in the ECG,
in the whereas
ECG, whereasin UA
in UA
In NSTEMI, ST/T changes may be present in the ECG, whereas in UA
they they
are usually absent
are usually and and
absent eveneven
if they are present,
if they are are
are present, usually transient.
usually transient.
they are usually absent and even if they are present, are usually transient.
FIGURE 2: Pathogenesis
FIGURE of ACS
2: Pathogenesis of ACS
FIGURE 2: Pathogenesis of ACS
Adapted with modification from Antman EM, Anbe DT, Armstrong PW et al. “ACC/AHA Guidelines
Adapted with modification
Adapted from Antman
with modification EM, Anbe
from Antman DT, Armstrong
EM, Anbe PW et
DT, Armstrong PW al.et“ACC/AHA Guidelines
al. “ACC/AHA Guidelines
for the management of patients with ST Elevation Myocardial Infarction” at www.acc.org
for thefor
management of patients
the management with ST
of patients Elevation
with Myocardial
ST Elevation Infarction”
Myocardial at www.acc.org
Infarction” at www.acc.org
3. PATHOGENESIS
3. PATHOGENESIS
3. PATHOGENESIS
ACS occurs due to atherosclerotic plaque rupture, fissure or ulceration
ACS ACS
occurs due due
occurs to atherosclerotic plaque
to atherosclerotic rupture,
plaque fissure
rupture, or ulceration
fissure or ulceration
with superimposed thrombosis and coronary vasospasm. Depending on
with with superimposed
superimposed thrombosis
thrombosis and and coronary
coronary vasospasm.
vasospasm. Depending
Depending on on
the acuteness, degree of occlusion and the presence of collaterals,
the acuteness,
the acuteness, degree
degree of occlusion
of occlusion and and
the the presence
presence of collaterals,
of collaterals,
patients can present as UA, NSTEMI or STEMI.
patients
patients can present
can present as UA,
as UA, NSTEMI
NSTEMI or STEMI.
or STEMI.
The aetiology of the plaque fissure or rupture is still unclear. Possible
The The aetiology
aetiology of plaque
of the the plaque fissure
fissure or rupture
or rupture is still
is still unclear.
unclear. Possible
Possible
causes include inflammation, infection, uncontrolled blood pressure and
causes
causes include
include inflammation,
inflammation, infection,
infection, uncontrolled
uncontrolled bloodblood pressure
pressure andand
smoking. ACS occurring de novo is called Primary UA/NSTEMI.
smoking.
smoking. ACSACS occurring
occurring de novo
de novo is called
is called Primary
Primary UA/NSTEMI.
UA/NSTEMI.
Occasionally UA/NSTEMI is secondary to a precipitating condition, which
Occasionally
Occasionally UA/NSTEMI
UA/NSTEMI is secondary
is secondary to atoprecipitating
a precipitating condition,
condition, which
which
is extrinsic to the coronary arterial bed. This is called secondary
is extrinsic
is extrinsic to the
to the coronary
coronary arterial
arterial bed.bed.
ThisThis is called
is called secondary
secondary
UA/NSTEMI and can occur due to:
UA/NSTEMI
UA/NSTEMI and occur
and can can occur
due due
to: to:
increased myocardial oxygen demand as occurring in fever,
increased
increased myocardial
myocardial oxygen
oxygen demand
demand as as occurring
occurring in in fever,
fever,
tachycardia and thyrotoxicosis
tachycardia
tachycardia and and thyrotoxicosis
thyrotoxicosis
reduced coronary blood flow due to hypotension
reduced
reduced coronary
coronary bloodblood
flow flow due to hypotension
duedelivery
to hypotension
reduced myocardial oxygen in anaemia or hypoxemia
reduced myocardial
reduced myocardial oxygenoxygen delivery
delivery in anaemia
in anaemia or hypoxemia
or hypoxemia
Secondary UA/NSTEMI is an important cause of ACS in the elderly.
Secondary
Secondary UA/NSTEMI
UA/NSTEMI is anisimportant
an important
causecause of ACS
of ACS in the
in the elderly.
elderly.
16
16
1616
4. DIAGNOSIS
4.1 History
The symptoms of UA/NSTEMI may be indistinguishable from that of

STEMI. These include:
Chest pain - This is the presenting symptom in most

patients. Chest pain or discomfort is usually retrosternal,
central or in the left chest and may radiate to the jaw or
down the upper limb. It may be crushing, pressing or burning
in nature. The severity of the pain is variable.
A significant number of patients, especially women, diabetics and

the elderly, present with atypical symptoms3. These include :
Dyspnoea without any history of chest pains.
Unexplained sweating, nausea and vomiting, syncope and

presyncope, fatigue and epigastric discomfort.
In patients with these presentation(s) and with a prior history of

coronary artery disease (CAD), a family history of premature
CVD, diabetes and other cardiovascular risk factors, the index
of suspicion of ACS should be high. Prior history of diabetes
and renal disease will influence management4,5.
4.2 Physical Examination
The objective of the physical examination is to identify:
possible causes,
precipitating causes and
consequences of UA/NSTEMI
Uncontrolled hypertension, anaemia, thyrotoxicosis, severe aortic

stenosis, hypertrophic cardiomyopathy and other co-morbid
conditions such as lung disease should be identified.
Presence of left ventricular failure (hypotension, respiratory

crackles or S3 gallop) and arrhythmias carry a poor prognosis.
Carotid bruits or peripheral vascular disease indicates extensive
atherosclerosis and a higher likelihood of concomitant CAD.
17
17
4.3 Electrocardiography
The ECG adds support to the diagnosis and provides prognostic

information6-11. A recording made during an episode of chest pain is
particularly valuable.
I, C It should be performed within 10 minutes of the patient’s arrival at

the Emergency Department.
Features suggestive of UA/NSTEMI are:
Dynamic ST/T changes

ST depression > 0.5 mm in 2 or more contiguous leads
T-wave inversion – deep symmetrical T-wave inversion
Other ECG changes include new or presumed new onset bundle

branch block (BBB)* and cardiac arrhythmias, especially sustained
ventricular tachycardia. Evidence of previous infarctions such as Q
waves may be present.
However, a completely normal ECG does not exclude the diagnosis

I, C
of UA/NSTEMI. Serial ECGs should be done as the ST changes
may evolve.
* New LBBB should be treated as STEMI
4.4. Cardiac Biomarkers
Cardiac troponins (troponin T or I) are the recommended

I, A
biomarkers. (Figure 3, pg 19) They are highly specific and sensitive
for myocardial injury and/or necrosis (infarction), and also provide
important prognostic information, there being a correlation between
the level of troponin and cardiac mortality and other adverse
cardiac events12-16. The troponin level may not be elevated if the
test is done early (<6 hours). To confidently exclude myocardial
necrosis (infarction), a repeat test needs to be done 6–12 hours
after admission. Troponin testing can be done in the laboratory
(quantitative) or with a hand held rapid semi-quantitative assay.
Blood levels may persist for 5–14 days after the acute event.
17
Non coronary
Non coronary causes
causes for
forelevated
elevatedtroponins
troponinsareareextremely
extremelyrare
rare . 17It. It may o
may occur
acute in acute
myocarditis, myocarditis,
acute pulmonaryacute pulmonary
embolism, embolism,
a dissecting aorticaaneurysm
dissecting
heart failureaortic
and aneurysm,
sometimesacute heartshock.
in septic failureSevere
and sometimes in
renal dysfunction ma
septic shock. Severe renal dysfunction may also cause raised
cause raised troponins in the absence of ACS. A raised level is however asso
troponins
with in thein absence
an increase of ACS. inAthese
all cause mortality raised level (Appendix
patients. is however II, pg 52)
associated with an increase in all cause mortality in these patients.
(Appendix II, pg 52) 18
18
Creatinine kinase (CK) and its MB fraction (CKMB) are also important
Creatinineofkinase
indicators (CK) and
myocardial its MB
necrosis fraction (CKMB)
(infarction). They areare also important
however, less
indicatorsand
sensitive of specific
myocardial necrosis
compared (infarction).
to cardiac troponins. They
CK are however,
and CKMB haveless
asensitive
shorter and
halfspecific
life and compared
hence are to cardiac troponins.
more useful thanCK and CKMB
troponins when have
a shorter reinfarction.
diagnosing half life and hence are more useful than troponins when
diagnosing reinfarction.
All patients with NSTEMI have raised troponins, however, the CKMB may
18,19
be normal in
All patients with10-20%
NSTEMI of have
theseraised
patients
troponins,. Ahowever,
raised CKMB in the
the CKMB may
18,19 18,19
presence
be normal of ainnormal
10-20% troponin level has
of these no prognostic
patients . A significance
raised CKMB . in the
presence of a normal troponin level has no prognostic significance 18,19.
Myoglobin is not cardiac specific. It can be detected as early as 2 hours
after the onset
Myoglobin of chest
is not pain.
cardiac A negative
specific. It cantestbewithin 4-8 hours
detected of chest
as early as 2painhours
is useful
after in ruling
the onset out pain.
of chest myocardial necrosis
A negative (infarction).
test within It should
4-8 hours of chest not
pain
however
is usefulbeinused as the
ruling outonly biomarker necrosis
myocardial to identify (infarction).
patients with It
NSTEMI.
should not
however be used as the only biomarker to identify patients with NSTEMI.
FIGURE 3: Time course of elevation of serum cardiac biomarkers in ACS

FIGURE 3: Time course of elevation of serum cardiac biomarkers in ACS
(Adopted from “Clinical Implications of the new definition of myocardial infarction”. John K French,
Harvey D White; Heart 2004;90:99–106)
(Adopted
4.5 Other from “Clinical
diagnostic Implications of the new definition of myocardial infarction”. John K French,
modalities
4.5 Other diagnostic Harveymodalities
D White; Heart 2004;90:99–106)
IIa, B Echocardiogram – LV systolic function is an important

IIa, B Echocardiogram – LV systolic function is an important
prognostic indicator in patients with UA/NSTEMI. Transient
prognostic indicator in patients with UA/NSTEMI. Transient
reversible regional wall motion abnormalities may be detected
reversible regional wall motion abnormalities may be detected
during ischemia.
during ischemia.
Key message:
Key message:
The diagnosis of UA/NSTEMI is based on history + dynamic ECG changes
The diagnosis of UA/NSTEMI
19 is based on history + dynamic ECG
(without persistent ST elevation), + raised cardiac biomarkers.
(without persistent ST elevation), + raised cardiac biomarkers.
In UA cardiac biomarkers are normal while in NSTEMI it is elevated.
In UA cardiac biomarkers are normal while in NSTEMI it is elevate
19 and prognostic significance I,A.
A raised troponin level has diagnostic
A raised troponin level has diagnostic and prognostic significance
19
5. RISK STRATIFICATION
5.1 Assessment of Risk
The initial evaluation should be used to provide information about the

diagnosis and prognosis. An attempt should be made to simultaneously
answer 2 questions:
What is the likelihood that the signs and symptoms represent ACS?
(Appendix III, pg 53)
What is the likelihood of an adverse clinical outcome – death, MI (or

recurrent MI), stroke, HF, recurrent symptomatic ischemia, and
serious arrhythmia?
In making a diagnosis of ACS one should consider the symptoms, ECG

abnormalities and cardiac biomarkers. The absence of risk factors does
not exclude a diagnosis of ACS.
5.2 Rationale for Risk Stratification
Patients with UA/NSTEMI have an increased risk of death, recurrent MI,

recurrent symptomatic ischemia, serious arrhythmias, heart failure and
stroke.
Early assessment would help in determining the:
prognosis of the patient
management strategies
- selection of the site of care (coronary care unit, monitored

step-down ward or outpatient setting)
- selection of appropriate therapy and the need for coronary

angiogram and revascularization
5.3 Risk Scores for prognosis of UA/NSTEMI
Several risk stratification scores have been developed and validated in

large patient populations. In clinical practice, 2 risk scores that are
commonly used are:
TIMI Risk Score 20,21 - it is less accurate in predicting events, but is

simple and widely accepted. ( Appendix IV, pg 54)
GRACE risk scores 22 (Appendix V, pg 55)
21
20
Both risk scores confer additional important prognostic value beyond

Both risk scores confer additional important prognostic value beyond
global risk assessment by physicians. These validated risk scores may
global risk assessment by physicians. These validated risk scores may
refine risk stratification, thereby improving patient care in routine clinical
refine risk23 stratification, thereby improving patient care in routine clinical
practice 23. We have proposed a simplified risk stratification model as
practice . We have proposed a simplified risk stratification model as
outlined in Flowchart 1, pg 3.
outlined in Flowchart 1, pg 3.
5.4 Risk Assessment for Bleeding
5.4 Risk Assessment for Bleeding
Hemorrhagic complications are an independent risk factor for subsequent
Hemorrhagic complications are an independent risk factor for subsequent
mortality in ACS patients and in those undergoing PCI. These patients can
mortality in ACS patients and in those undergoing PCI. These patients can
be identified by:
be identified by:
ACUITY HORIZONS-AMI24 Bleeding Risk Score

ACUITY HORIZONS-AMI24 Bleeding Risk Score
CRUSADE Bleeding Risk Score25
CRUSADE Bleeding Risk Score25
These scores are calculated based on age, clinical status and
These scores are calculated based on age, clinical status and
hemodynamics at presentation, serum creatinine and hematocrit level and
hemodynamics at presentation, serum creatinine and hematocrit level and
the use and combinations of antiplatelets and anticoagulants.
the use and combinations of antiplatelets and anticoagulants.
Key messages
Key messages
Risk stratification is important for prognosis and to guide
Risk stratification is important for prognosis and to guide
management I,A .
management I,A.
6. TRIAGE
6. TRIAGE
Triage helps in identifying patients who need urgent care. Rapid
Triage helps in identifying patients who need urgent care. Rapid
assessment and aggressive management of high risk patients may result
assessment and aggressive management of high risk patients may result
in an improvement in outcome and a reduction in mortality.
in an improvement in outcome and a reduction in mortality.
Rapid assessment includes:
Rapid assessment includes:
evaluation of patient’s clinical status:
evaluation of patient’s clinical status:
- mental status
- mental status
- comfort status
- comfort status
- respiration
- respiration
- peripheral perfusion
- peripheral perfusion
vital signs:
vital signs:
- blood pressure
- blood pressure
- rate and volume of pulse
- rate and volume of pulse
- respiratory rate
- respiratory rate
history:
history:
- presence and severity of chest pains
- presence and severity of chest pains
22
22
21
- past history of coronary and vascular events, interventions

and surgery
- risk factors
 hypertension
 diabetes mellitus
 dyslipidaemia
 previous medications – eg anti-anginals, antiplatelets
 family history of premature CAD
ECG
cardiac biomarkers
- troponins
- CK-MB
Based on the above clinical assessment, patients can be risk stratified to

(Flowchart 1, pg 3) :
I. Intermediate/high risk
II. Low risk
The TIMI Risk Score and the Grace Risk Score (see 5.3) are also used to
provide additional prognostic information.
The appropriate management, which includes the rapidity and the degree
of invasiveness, is generally guided by the risk status of the patient. There
is evidence that high risk patients have increasing benefit from therapies
(like low molecular weight heparin (LMWH), glycoprotein (GP) IIb/IIIa
inhibitors) and an invasive strategy.
The recommended therapy based on risk-stratification is as in Flowchart

1, pg 3.
Key messages
Intermediate/high risk patients benefit from early angiography and

revascularization I,A.
7. Management of UA/NSTEMI
The goals of management are:
Immediate relief of ongoing ischemia and angina

Prevention of recurrent ischemia and angina
Prevention of serious adverse cardiac events
23
22
7.1 Pre-hospital Management
Based on the triage:
Based on the triage:
 Ifonthe
Based thehistory
triage: is suggestive of ACS :
 If the - history
Give soluble aspirin 300
is suggestive of mg
ACS crushed
: stat
 If the - history
Give sublingual
soluble GTN300
is suggestive
aspirin of mg
ACS :
crushed stat
- DoGive12sublingual
lead ECG
soluble and300
aspirin
GTN cardiac biomarkers
mg crushed stat
- DoGive12sublingual
lead ECGGTN and cardiac biomarkers
- Do 12 lead ECG and cardiac biomarkers
If the ECG and cardiac biomarkers are suggestive of ACS
If the- ECGGive and clopidogrel
cardiac300 mg stat if are
biomarkers available.
suggestive of ACS
If the -- ECG
Sendand
Give the cardiac
patient300
clopidogrel to the
mgnearest
biomarkers
stat if are healthcare
suggestive
available. facility where
of ACS
definitive
-- Give the treatment
Sendclopidogrelpatient300to can be
mgnearest
the statgiven.
if available.
healthcare facility where
- Send
definitivethe treatment
patient to canthe nearest
be given.healthcare facility where
If the ECG definitive treatment
and cardiac can be given.
biomarkers are inconclusive for ACS
If the- ECG Lowand riskcardiac
patients : they canare
biomarkers be inconclusive
referred as outpatient
for ACS
If the- ECG for
Low cardiac
and assessment.
riskcardiac
patients biomarkers
: they(Figcan1,are
pginconclusive
be 5) for ACS
referred as outpatient
- Low
Intermediate
for cardiac / High: Risk
risk patients
assessment. they(Figpatients
can1, be : shouldasbeoutpatient
referred
pg 5) admitted
.Intermediate
- for cardiac assessment.
/ High Risk (Fig 1, pg 5): should be admitted
patients
- - Intermediate
. / High Risk patients : should be admitted
7.2 In-Hospital
- . Management (Table1, pg 4)
-
7.2 In-Hospital Management (Table1, pg 4)
7.2.1 In-Hospital
7.2 Initial management Management – General Measures
(Table1, pg 4)
7.2.1 Initial management – General Measures
Following
7.2.1 Initial – General Measures
risk stratification:
management
Following risk stratification:
low risk patients
Following may be treated as outpatient.
risk stratification:
low risk patients may be treated as outpatient.
I, C High
low risk riskpatients
patients may preferably
be treated should be admitted to CCU/HDU
as outpatient.
I, C High
with risk patients
continuous ECG preferably
monitoring.should be admitted to CCU/HDU
I, C High risk patients
with continuous ECG preferably
monitoring.should be admitted to CCU/HDU
supplemental
with continuous oxygen should be given to maintain SpO2 >90%,
ECG monitoring.
I, B supplemental
in patients with oxygen should be failure,
left ventricular given torespiratory
maintain SpO 2 >90%,
distress or
I, B supplemental
in patients
having high with oxygen
risk should
left ventricular
features be failure,
given torespiratory
for hypoxemia. maintain SpO 2 >90%,
distress or
I, B in patients
having high with left ventricular
risk features failure, respiratory distress or
for hypoxemia.
for painhigh
having relief,
riskmorphine
features for (intravenous
hypoxemia.2 mg to 5 mg) together
IIa,B
for pain
with relief, morphine
concomitant (intravenous
intravenous anti-emetic 2 mg
maytobe5given.
mg) together
IIa,B for pain relief, morphine (intravenous 2 mg tobe5given.
mg) together
IIa,B with concomitant intravenous anti-emetic may
7.2.2. Medications
with concomitant - Antiplatelet
intravenous agents
anti-emetic may be given.
7.2.2. Medications - Antiplatelet agents
7.2.2.1 Oral antiplatelet
7.2.2. Medications agents
- Antiplatelet agents
7.2.2.1 Oral antiplatelet agents
7.2.2.1.1
7.2.2.1 Acetylsalicylic
Oral antiplateletacid (ASA)
agents
7.2.2.1.1 Acetylsalicylic acid (ASA)
Recommended
I, A 7.2.2.1.1 Acetylsalicylic loading dose: 300 mg of soluble/chewable
acid (ASA)
26,27
I, A aspirin
Recommended . Enteric
loadingcoated
dose: aspirin
300 is mgnotof recommended
soluble/chewablefor
I, A initial
Recommended
aspirin 26,27
loading dose because
loading
. Enteric ofaspirin
dose:
coated it’s300
slowis onset
mg of action.
notof recommended
soluble/chewablefor
26,27
aspirinloading
initial . Enteric coatedofaspirin
dose because it’s slow isonset of action.
not recommended for
24
initial loading dose because of it’s slow onset of action.
24
24
23
I, A Maintenance dose: 75-150 mg daily of soluble or enteric

coated aspirin 26,27
Aspirin in excess of 300-325 mg per day is associated with

increased risk of minor bleeding without greater efficacy 27.
7.2.2.1.2 Adenosine Diphosphate (ADP) Receptor

Antagonists
These include:
I, A Clopidogrel – loading dose: 300 to 600 mg, maintenance dose:

75 mg/day 28,29
IIa, B Ticlopidine – dose: 250 mg b.i.d. It is associated with

neutropenia in 1% of patients 30. Due to this safety reason, it is
not preferred. Patients on ticlopidine should have their total
white cell count monitored regularly for the initial 3 months.
I, B Prasugrel – loading dose 60 mg, maintenance dose: 10 mg/day
- To date, outcome data is only available in ACS patients

undergoing PCI 31. It is recommended to be given after
coronary angiography in patients planned for PCI.
- Its use in other subsets of patients is still being evaluated.
- It is not recommended for patients >75 years old, <60 kg

weight, past history of transient ischemic attack or stroke
due to a higher risk of major bleeding.
I, B Ticagrelor – loading dose : 180 mg, maintenance dose : 90 mg

bid.
- Ticagrelor was shown to significantly reduce cardiovascular

endpoints when compared to clopidogrel in patients with
ACS 32.
- This agent is short acting and thus can be used in patients

who may need surgery without increasing the risk of
bleeding.
- Potential drawback is dyspnoea and transient ventricular

pauses during the first week. This was rarely associated
with symptoms or need for a pacemaker. There was also a
small increase in non CABG related major bleeding32.
25
24
with symptoms or need for a pacemaker. There was also a
management of Unstable Angina/Non 32 ST
small increase in non CABG related major bleeding .
Elevation
withMyocardial Infarction
symptoms or need (UA/NSTEMI)
for a pacemaker. 2011
There was also a
7.2.2.2 Intravenous
small increase Antiplatelet
in non CABG Therapy
related major bleeding 32. (GP)
– Glycoprotein
IIb/IIIa Inhibitors
7.2.2.2 Intravenous Antiplatelet Therapy – Glycoprotein (GP)
IIb/IIIa These include:
Inhibitors
Abciximab
These include:
Tirofiban
Abciximab
Eptifibatide
Tirofiban
TheseEptifibatide
agents may be used in high risk patients awaiting transfer
to a PCI facility for an early invasive strategy. Its routine use as
These agents may be used in high riskno
patients 33,34
“upstream therapy” prior to PCI is now longer awaiting
practicedtransfer
.
to a PCI facility for an early invasive strategy. Its routine use as
33,34
7.2.3.“upstream therapy”
Anticoagulant prior to PCI is now no longer practiced
Therapy .
7.2.3. Anticoagulant Therapy

These include: (Table 2, pg 27)
I, A These include: (Table

Unfractionated 2, pg(UFH)
heparin 27)
I, A Unfractionated heparin (UFH)

I, A Low Molecular Weight Heparin (LMWH)-Enoxaparin 35,36,37
Anti Xa inhibitor-Fondaparinux
I, A Low Molecular Weight Heparin (LMWH)-Enoxaparin 35,36,37
I, A Anti- XaItinhibitor-Fondaparinux
is best used in UA/NSTEMI patients treated
conservatively 38,39.
I, A - It isis associated
best usedwith in an
UA/NSTEMI
increase in patients treated
catheter-related
38,39
conservatively
thrombus .
and coronary angiographic complications.
- It is is associated with an increase
not recommended as the solein catheter-related
anticoagulant
thrombus 38,39 coronary angiographic complications.
during PCIand .
- It is notin recommended
If used UA/NSTEMI and as the
the patient
sole anticoagulant
requires an
38,39
during
invasive PCI . UFH should be given during the
strategy,
- If used in UA/NSTEMI
procedure. When used and the itpatient
in PCI, requireswith
is associated an
invasive strategy, UFH 38,39,40
lower bleeding rates thanshould
LMWHbe given
. during the
procedure. When used in PCI, it is associated with
38,39,40
Presentlylower bleeding
newer oralrates
antithan
Xa LMWH
inhibitors are . undergoing
evaluation for ACS.
Presently newer oral anti Xa inhibitors are undergoing
evaluation
Anti for ACS.
IIa inhibitors – Bivalirudin
Anti- IIaItinhibitors
may be used– Bivalirudin
as a substitute for heparin in patients
I, B
with heparin-induced thrombocytopenia (HIT) 41.
I, B - It is may be used as
reasonable a substitute
to use foras
bivalirudin heparin in patients
an alternative to
41
I, A with
UFHheparin-induced thrombocytopenia
and GP IIb/IIIa inhibitors (HIT)
in patients .
undergoing
- PCI 42-45
It is reasonable
. to use bivalirudin as an alternative to
I, A - UFH and GP IIb/IIIa
It is associated inhibitors
with less in patients undergoing
bleeding.
42-45
- PCI To date .it is not yet available in Malaysia.
- It is associated with less bleeding.
- To date it is not yet available 26 in Malaysia.
26
25
Key messages
High risk patients preferably should be continuously monitored in

CCU/HDU I,C.
Intermediate/high risk patients should be given ASA I,A,clopidogrel I,A

(or prasugrel I,B or ticagrelor I,B) and UFH I,A or LMWH I,A or
fondaparinux I,A. Prasugel may be given after coronary angiography in
high risk patients undergoing PCI I,B. (Table 1, pg 4)
Low risk patients should be given aspirin I,A and risk stratified as
outpatient with non invasive tests for reversible ischemia. (Fig 1, pg 5)
27
26
TABLE 2: Doses of Anticoagulant Agents in UA/NSTEMI and during PCI*35-39,42-45
AGENT DOSING REGIMEN

UFH
UA/NSTEMI Initial IV bolus : 60 IU/kg (max 4000 IU) followed by infusion of 12
IU/kg/hour (max 1000 IU/hour) adjusted to maintain aPTT 1.5-2.0x
normal. Duration of therapy : 2-8 days35-37
During PCI Loading Dose :

Empirical loading dose: 5000-10000 IU, or
Weight adjusted loading dose:
- Not receiving GP IIb/IIIa inhibitors: 70-100 IU/kg
- Receiving GP IIb/IIIa inhibitors : 50-70 IU/kg
Further doses if procedure is > 1 hour may be by:

Empirical weight adjusted doses :
- Not receiving GP IIb/IIIa inhibitors: 60 IU/kg
- Receiving GPIIb/IIIa inhibitors: 50 IU/kg
Guided by ACT monitoring
- Not receiving GP IIb/IIa inhibitors maintain ACT:
250-300 secs
- Receiving GP IIb/IIIa inhibitors maintain ACT: 200 secs
Enoxaparin
UA/NSTEMI Initial 30 mg IV bolus and then 15 minutes later by:
sc 1.0 mg/kg every 12 hours if age less than 75 years
sc 0.75 mg/kg every 12 hours if age 75 years and above
Duration of therapy : 2-8 days 35-37
During PCI Depends on prior enoxaparin use:

No prior use : 0.5-0.75 mg/kg IV bolus
Prior use within 8 hours of PCI: no additional dose
Prior use between 8-12 hours of PCI: 0.3 mg/kg IV.
Supplemental UFH may also be given during PCI
Bivalirudin
UA/NSTEMI 0.1 mg/kg bolus and 0.25 mg/kg/hour infusion
During PCI Depends on prior bivalirudin/UFH use:

Prior treatment with bivalirudin: additional 0.5 mg/kg bolus
and increase infusion rate to 1.75 mg/kg/hour
Prior treatment with UFH: wait 30 mins then 0.75 mg/kg
bolus and infusion of 1.75 mg/kg/hour
No prior treatment: 0.75 mg/kg bolus and infusion of 1.75
mg/kg/hour
Fondaparinux
UA/NSTEMI 2.5 mg sc daily for 8 days or duration of hospitalization 38,39
During PCI If used during PCI, additional 50-60 IU/ kg UFH is recommended.
* For doses in renal impairment see section 9.3, Table 6, pg 35
28
27
7.2.4 Anti-Ischemic Drug Therapy
These agents may be given either for relief of ischemia (symptoms)

or for prognosis.
7.2.4.1 Nitrates (Table 3, pg 29)
I, C Sublingual glyceryl trinitrate (GTN 0.5 mg) – Patients with

UA/NSTEMI with ongoing chest pain should receive sublingual
GTN 0.5 mg every 5 minutes for a total of 3 doses. If symptoms still
persist, intravenous GTN should be considered.
I, C Intravenous nitrates – may be administered in the following

situations:
No symptom relief after 3 doses of sublingual GTN

Presence of dynamic ECG changes
Presence of left ventricular failure
Concomitant high blood pressure.
Oral nitrates may be given after 12 to 24 hours of pain free period.

Rebound angina may occur with abrupt cessation of nitrates 46.
Contraindications to nitrate therapy:
Hypotension (SBP< 90 mmHg)

RV infarction
History of phospho-diesterase 5 inhibitors ingestion
(depending upon the half-life of the agent)
7.2.4.2 β-blockers (Table 4, pg 29)
I, B In the absence of contraindications, β-blockers should be

administered early.
Contraindications for β-blockers in UA/NSTEMI 47 :
Patients with marked first-degree AV block (PR interval

greater than 0.24s).
Second- or third-degree AV block.
History of bronchial asthma
Severe peripheral arterial disease
Acute decompensated LV dysfunction
Cardiogenic shock.
29
28
Table 3: Recommended dosages of Nitrates in UA/NSTEMI*
Compound Route Dosage Time of Onset

Table 3: Recommended dosages of Nitrates in UA/NSTEMI*
0.3 - 0.6 mg, can repeat up
Compound Sublingual
Route to 3 times at 5 minute
Dosage 2 minute
Time of Onset
intervals
0.3 - 0.6 mg, can repeat up
Intravenous
Sublingual to53–times
200 µg/min*
at 5 minute 12
minute
minute
Nitroglycerine,
0.4 – 0.8 mgintervals
per metered
Glyceryl
trinitrate dose, no more than 3
Intravenous
GTN Spray 5 – 200 µg/min* 2 1minute
minute
Nitroglycerine, sprays at 5 minute
Glyceryl intervals
0.4 – 0.8 mg per metered
trinitrate dose, no more than 3
GTN Spray 2.5 – 20 mg over 12 hours 2 minute
Transdermal patch sprays at 5 minute 1 – 2 hours
on, then 12 hours off
intervals
Intravenous 2 – 12 mg / hour 1 minute
2.5 – 20 mg over 12 hours
Isosorbide Transdermal patch 1 – 2 hours
dinitrate 10 on,
– 20then
mg,12
2 –hours off
3 times
Oral 30 – 60 minutes
daily
Intravenous 2 – 12 mg / hour 1 minute
Isosorbide
Isosorbide
dinitrate Oral (LA) – 20 mg,
10 30-60 mg 2 – 3 times
daily,
mononitrate Oral ( max 120 30 – 60 minutes
dailymg )
*The dose of IV nitrates should be titrated every 5 – 10 minutes until symptoms and/or
Isosorbide
Oraland
ischaemia is relieved (LA) 30-60 mg daily,
the desired haemodynamic response is obtained
mononitrate ( max 120 mg )
*As stated in MIMS Malaysia
*The dose of IV nitrates should be titrated every 5 – 10 minutes until symptoms and/or
ischaemia is relieved and thedosages
Table 4: Recommended of β -blockersresponse
desired haemodynamic is obtained
in UA/NSTEMI*
Type Initiation dose Target dose
Table 4: Recommended dosages of β -blockers in UA/NSTEMI*
Metoprolol 25 mg bd 100 mg bd
Type
Atenolol Initiation
25 mg oddose Target
100 mg dose
od
Metoprolol
Bisoprolol 25 mg
1.25 mg od
bd 100
10 mgmg
odbd
Atenolol
Carvedilol 25 mg
3.125 mg od
bd 100
25 mgmg
bdod
Bisoprolol
*As stated in MIMS Malaysia 1.25 mg od 10 mg od
Carvedilol 3.125 mg bd 25 mg bd
30
30
29
7.2.4.3
7.2.4.3
7.2.4.3 Calcium
Calcium
Calcium Channel
Channel
Channel Blockers
Blockers
Blockers (Table(Table
5, (Table
5, pg
pg 30) 5, 30)
pg 30)
Calcium
Calcium
Calcium channel
channelchannelblockers
blockers
blockers (CCB)
(CCB) (CCB)
may may
be may
be in
used be
used
used
in UA/NSTEMI
in UA/NSTEMI
UA/NSTEMI in the in the
in the
following
following
following situations:
situations:
situations:
I, BI, B I, B Verapamil
Verapamil
Verapamil or diltiazem
or diltiazem
or diltiazem as anasalternative
an
as an
alternative
alternative
to patients
to patients towho
patients
arewho
notwho
areare
not not
able
able toable
to tolerate
to tolerate
tolerate or whoor who
or who
have havehave
contraindication
contraindication
contraindication β48–blockers.
to βto–blockers.
to β –blockers. 48 48
IIa,CIIa,C Continuing
IIa,C Continuing
Continuing
or recurring
or orrecurring
recurring
angina
angina
despite
anginadespite
adequate
despiteadequate
adequate
doses ofdoses
dosesof of
nitrates
nitrates
nitratesβ-blockers
andand andβ-blockers
β-blockers
– verapamil,
– verapamil,
– verapamil,
diltiazem,
diltiazem,
diltiazem,
slow release
slow
slow
release
release
nifedipine
nifedipine
nifedipine
andand
amlodipine.
and
amlodipine.
amlodipine.
Prinzmetal’s
Prinzmetal’s
Prinzmetal’s
angina
angina
(variant
angina(variant
angina)
(variant
angina)
angina)
III,III, Short-acting
A AIII, A Short-acting
Short-acting
dihydropyridine
dihydropyridine
dihydropyridine
CCB CCB
should
CCB
should
beshould
avoided
be avoided
be avoided
Table
Table
Table
5: 5:
Recommended
Recommended
5: Recommended
dosages
dosages
dosages
of Calcium
of Calcium
of Channel
Calcium
Channel
Blockers
Channel
Blockers
inBlockers
UA/NSTEMI*
in UA/NSTEMI*
in UA/NSTEM
Drug
Drug
Drug Dose Dose
Dose
Diltiazem
Diltiazem
Diltiazem Immediate
Immediate
Immediate release
release release
30-90 30-90
mg 30-90
tds mg mg
tds tds
Slow Slow
release
Slow
release
100-200
release
100-200
mg
100-200
od mg mg
od od
Verapamil
Verapamil
Verapamil Immediate
Immediate
Immediate release
release release
40-80 40-80
mg 40-80
tds mg mg
tds tds
Slow Slow
Slow
release
release release
120-240
120-240 120-240
mg od mg mg
od od
Amlodipine
Amlodipine
Amlodipine 2.5-10
2.5-10 2.5-10
mg odmg mg
od od
Nifedipine
Nifedipine
Nifedipine Slow Slow
release
Slow
release
30-90
release
30-90
mg 30-90
od mg mg
od od
*As*As *As
stated
stated instated
in MIMS
MIMS inMalaysia
MIMS
Malaysia
Malaysia
7.2.5
7.2.5 7.2.5
Lipid
Lipid Lipid
Modifying
Modifying
Modifying Drugs
Drugs Drugs
Current
Current
Current data
data data
indicate
indicateindicate
that thatthat
early early
early
initiation
initiation initiation
of highofdose
high
of high
dose
statindose
statin
statin
therapy therapy
therapy
I,A A I, A soon
soon after
soon
after admission
after
admission for for
admission UA/NSTEMI
UA/NSTEMI
for UA/NSTEMI cancan
can reducereduce
major major
reduce
adverse adverse
major adverse
49-54 49-5449-54
cardiac
cardiac events
events
cardiac due due
eventsto itstopleotropic
due its
to pleotropic
effectseffects
its pleotropic effects
. Patients
. Patients
.with
Patients
ACS withwith
ACS ACS
undergoing
undergoing
undergoing
PCI,PCI, have
PCI,havealso
havealso
been
also
been
found
been found
to found
benefit
to tobenefit
with
benefit
thewithwith
the the
administration
administration
administration
of high
of high
of
dosehigh
dose
statins
dose
statins
before
statins
before
andbefore
within
andand
10within
days
within
10
of days
10
the days
of the
of the
55-5755-5755-57
procedure
procedure
procedure . . .
The
The
statins
The
statins
statins
thatthat
have
that
have
been
have
been
studied
been
studied
instudied
UA/NSTEMI
in UA/NSTEMI
in UA/NSTEMI
to date to
are:
date
to date
are:are:
Atorvastatin – 80–mg
Atorvastatin
Atorvastatin 80–od
mg
80 mg
od od
Simvastatin
Simvastatin– 40–mg
Simvastatin 40–od
mg
40 mg
od od
31 31 31
30
7.2.6Angiotensin
7.2.6 AngiotensinConverting
ConvertingEnzyme
EnzymeInhibitor
Inhibitor(ACE-I)/ARB
(ACE-I)/ARB(Table
(Table
7,7,pgpg39)
39)
These
Theseshould
shouldbebeconsidered
consideredearly
earlyforforpatients
patientswith
withLV
LVdysfunction
dysfunction
I, A
I, A 55
and diabetes 55
anddiabetes . .
Key
Keymessages
messages
Patients
Patientsshould
shouldbebetreated
treatedwith
withoptimal
optimalmedical
medicaltherapy.
therapy.
(Table
(Table1,1,pgpg4)4)
I,C I,B I,C
Nitrates , ,β-blockers
Nitrates I,C β-blockers I,B+ +CCBs
CCBs I,Care
aregiven
givenforforrelief
reliefofof
ischemia.
ischemia.
Statins I,AI,Aand ACE-I (for LV dysfunction, LVEF < 40%) I,AI,Aare
Statins and ACE-I (for LV dysfunction, LVEF < 40%) are
given for prognosis.
given for prognosis.
8. Revascularization Strategies
8. Revascularization Strategies
There is a strong rationale for early revascularization in
There is a strong rationale for early revascularization in
intermediate/high risk patients with UA/NSTEMI 56,57 . (Flowchart 1,
intermediate/high risk patients with UA/NSTEMI 56,57. (Flowchart 1,
pg 3, Appendix IV, pg 54) Contemporary antiplatelet and
pg 3, Appendix IV, pg 54) Contemporary antiplatelet and
anticoagulant therapies have reduced the early hazard of PCI.
anticoagulant therapies have reduced the early hazard of PCI.
With increasing procedure experience, technological improvements
inWith
PCI increasing procedure experience,
and the development technological
of new antiplatelet improvements
and anticoagulant
in PCI and the development of new antiplatelet
regimens there is a general trend for early revascularization and anticoagulant
in
regimens
these there
patients is a general
following trend for
optimal medical early revascularization in
therapy.
these patients following optimal medical therapy.
8.1. Routine early invasive management 58-61
8.1. Routine early invasive management 58-61
I, B Urgent (as soon as possible after hospital presentation) 62 –
62
I, B Urgent (as
coronary soon as possible after hospital
angiography/revascularization patients with –
for presentation)
coronary orangiography/revascularization
refractory recurrent angina associated for with patients
dynamic STwith
refractoryheart
deviation, or recurrent angina
failure, life associated
threatening with dynamic
arrhythmias and/ orST
deviation, heart
hemodynamic failure, life threatening arrhythmias and/ or
instability
hemodynamic instability
I, A Early (<72 hours) coronary angiography/revascularization- in
I, A Early (<72
patients with hours) coronary
high-risk featuresangiography/revascularization-
as predicted by a positivein
biomarker assay,
patients with ST segment
high-risk featureschanges or a high
as predicted by risk score
a positive
58-61
according
biomarker to assay,
the TIMIST scale or equivalent
segment changes or . a high risk score
according to the TIMI scale or equivalent 58-61.
IIb, B
Routine invasive evaluation is not recommended in low risk
58-61
patients .
Routine invasive evaluation is not recommended in low risk
IIb, B
patients 58-61.
However these patients are recommended to have non-invasive
assessment
However thesefor inducible
patients or
aresilent ischemia. to have non-invasive
recommended
assessment for inducible or silent32
ischemia.
32
31
8.2 8.2Routine
Routine
earlyearly
conservative
conservative
management
management
(selective
(selective
invasive
invasive
63,64,65
63,64,65
therapy)
therapy)
I, A I, A
TheThe
use use
of aggressive
of aggressive
anticoagulant
anticoagulant and antiplatelet
and antiplatelet
agentsagents
has has
alsoalso
reduced
reducedthe incidence
the incidenceof adverse
of adverse outcomes
outcomes
in patients
in patients
63,64,6563,64,65
managed
managed conservatively
conservatively . . Selective
Selectivecoronary coronary
angiography/revascularization
angiography/revascularization is indicated
is indicated
for those
for those
who cannot
who cannot
be be
stabilized
stabilized
medically
medically
or inor whomin whom objective
objective
evidence
evidence
of of
significant
significant
ischemia
ischemia
is provoked
is provoked
in theinsub theacute
sub acute
phase.phase.
A conservative
A conservative
strategy
strategy
is recommended
is recommendedfor women
for women
who are
who are
IIa, AIIa, A 66
stabilized
stabilized
and and
remain
remain
biomarker
biomarker
negative . 66.
negative
An early
An early
invasive
invasive
or conservative
or conservative
therapy
therapy
is a reasonable
is a reasonable
option option
IIa, AIIa, A 66 66
for men
for men
who who
are stabilized
are stabilized
and remain
and remain
biomarker
biomarker
negative .
negative .
Patients
Patients
with with
UA/NSTEMI
UA/NSTEMItreatedtreated
conservatively
conservatively
are atare
riskatofrisk of
developing
developing
recurrent
recurrent
adverse
adversecardiac
cardiac
events.
events.
Thus Thus
these these
patients
patients
needneed
to beto evaluated
be evaluated periodically
periodically
for reversible
for reversible
ischemia
ischemia
usingusing
non non
invasive
invasive
tests.tests.
If ischemia
If ischemia
is present,
is present,
they they
should
should
be be considered
considered for forcoronary
coronaryangiography
angiographyand and
revascularization.
revascularization.
KeyKey
messages
messages
Patients
Patients
with with
refractory
refractory
angina
angina
and/ and/
or hemodynamically
or hemodynamically
unstable
unstable
should
should be be considered
considered for urgent
for urgent coronary
coronary angiography
angiography and and
I,C
revascularization
revascularization. I,C.
Intermediate/high
Intermediate/highrisk risk
patients
patientsshould should
be considered
be considered for early
for early
I,A I,A
invasive
invasive
strategy
strategy
(<72(<72
hours)hours). If admitted
. If admitted
to a non-PCI
to a non-PCI
centre,centre,
they they
I,B I,B
should
should
be considered
be consideredfor transfer
for transfer to a PCIto a centre
PCI centre. (Flowchart
. (Flowchart
1, 1,
pg 3)
pg 3)
I,C I,C
LowLow
risk risk
patients
patients
should
should
be assessed
be assessed
non-invasively
non-invasively
for ischemia
for ischemia
. .
(Fig(Fig
1, pg1,5)pg 5)
9 9 UA/NSTEMI
UA/NSTEMI IN SPECIAL
IN SPECIAL
GROUPS
GROUPS
All patients
All patients
should
should
receive
receive
optimal
optimal
medical
medical
therapy.
therapy.
(Table(Table
1, pg 4)
1, pg 4)
9.1 9.1UA/NSTEMI
UA/NSTEMI
in the
in Elderly
the Elderly
Cardiovascular
Cardiovascular
morbidity
morbidity
and mortality
and mortality
increases
increases
by 70%
by for
70%every
for every
10 10
yearyear
increase
increase in 18,67-68
in age age18,67-68
. .
33 33
32
9.1.1
9.1.1 Clinical
Clinicalpresentation:
presentation:
AA high
high index
index ofof suspicion
suspicion isis necessary
necessary to make a diagnosis
diagnosis of
of
UA/NSTEMI
UA/NSTEMI inin elderly
elderly patients.
patients. Atypical
Atypical presentations
presentations occur more
more
frequently.
frequently.These
Theseinclude:
include:
dyspnoea
dyspnoea
diaphoresis
diaphoresis
nauseaand
nausea andvomiting
vomiting
neurological
neurological symptoms
symptoms such
such as
as acute
acute confusional states
states and
and
syncope
syncope
ACS frequentlydevelops
ACSfrequently develops as as aa “secondary”
“secondary” coronary
coronary event in the setting
setting
ofofanother
anotheracute
acute illness
illness e.g.
e.g. pneumonia.
pneumonia. The
The elderly often are in heart
heart
failure
failureatatthe
thetime presentation 69
timeofofpresentation 69
.. The
The ECG‘s
ECG‘s may be non diagnostic.
diagnostic.
9.1.2.
9.1.2. Management
Management
There
Thereisislimited
limitedtrial
trial data
data to
to guide
guide management
management in the elderly especially
especially
ininthe
thesetting
setting ofof advanced
advanced age age (more
(more than
than 75 years) or significant
significant co-
co-
morbidity
morbidity(e.g.
(e.g.prior
prior stroke,
stroke, renal
renal impairment).
impairment). One should consider
consider the
the
biological
biological ageage rather
rather than
than the
the chronological
chronological age of the patient when
when
making
makingmanagement
management decisions.
decisions. The
The elderly
elderly are a heterogenous group
group
and
andthe
therisk
risk benefit
benefit ratio
ratio of
of each
each intervention
intervention should be individualized.
individualized.
Creatinine
Creatinine clearance
clearance should
should bebe calculated
calculated to enable appropriate drugdrug
dosing.
dosing.(Appendix
(AppendixVI,pgVI,pg56)56)
I, I,AA Bothaspirin
Both aspirinand
and clopidogrel
clopidogrel (especially
(especially in those undergoing
undergoing PCI)PCI)
confergreater
confer greaterabsolute
absolute and
and relative benefits in the elderly 70,71
relative benefits 70,71
..
I, I,BB Prasugrel should

Prasugrel should be
be avoided
avoided in
in patients
patients older than 75 years
years in
in
view
viewofofthe
thebleeding risk 31
bleedingrisk 31
..
I, I,AA
InInaameta-analysis,
meta-analysis,both
both UFH
UFH and
and LMWH
LMWH were equally effective
effective in
in
the elderly7272. .However
theelderly However bleeding
bleeding risk
risk is
is higher with both agents.
agents.
I, I,BB Elderly
Elderlypatients
patientshave
have more
more bleeding
bleeding complications use of
complications with the use of
GPIIb/IIIa inhibitors 73,74
GPIIb/IIIainhibitors 73,74
.. IfIf required,
required, the
the dose should be adjusted
adjusted
according
accordingtotothe
therenal
renalfunction.
function.
I, I,AA The
The elderly
elderly have
have greater
greater in-hospital
in-hospital and long term benefits
benefits with
with
an
anearly
earlyinvasive strategy 75-79
invasivestrategy 75-79
.. In
In some
some trials, all the benefits of
of an
an
early invasive strategy were in the elderly rather than in younger
patients 75. However there is an increased
34
34 risk of major bleeding 80.
When selecting patients for an early invasive strategy, the risk

benefit ratio must be considered. For patients with multi vessel
33
disease and not suitable for CABG, partial revascularization of the
Elevation
early
early Myocardial
earlyinvasive
invasive
invasivestrategy
strategy Infarction
strategywere
were
werein
ininthe
the (UA/NSTEMI)
theelderly
elderly
elderlyrather
rather
ratherthan
than
thaninin2011
inyounger
younger
patients75
patients
patients 7575
.. However
.However
Howeverthere
there
thereisisisan
an
anincreased
increased
increasedrisk
risk
riskof
of
ofmajor
major bleeding8080. .
majorbleeding
bleeding
When
When
Whenselecting
selecting
selectingpatients
patients
patientsfor
for
foran
an
anearly
early
earlyinvasive
invasive
invasivestrategy,
strategy,
strategy, the
the risk
risk
benefit
benefit
benefitratio
ratio
ratiomust
must
mustbebe
beconsidered.
considered.
considered.For
For
Forpatients
patients
patientswith
with
withmulti
multi
multivessel
vessel
disease
disease
diseaseand and
andnot
not
notsuitable
suitable
suitablefor
for
forCABG,
CABG,
CABG,partial
partial
partialrevascularization
revascularization
revascularizationofofthe
the
culprit
culprit
culpritlesion
lesion
lesionmay
may
maybebe
beaaaconsideration.
consideration.
consideration.
Long
Long term
Long term management
term management post
management post discharge
post discharge should
discharge should include
should include
medications
medications that
medications that have
that have been
have been proven
been proven beneficial
proven beneficial inin
beneficial in secondary
secondary
secondary
prevention.
prevention.
prevention.
9.2
9.2 UA/NSTEMI
UA/NSTEMIin
UA/NSTEMI ininWomen
Women
Women
Women
Womendevelop
developCAD
develop CADabout
CAD aboutaaadecade
about decadelater
decade laterthan
later thanmen
than menat
men ataaatime
at timewhen
time when
they
theyare
areolder
olderand
older andhave
and havemore
have moreco-morbidity
more co-morbiditysuch
co-morbidity suchas
such asobesity,
as obesity,diabetes,
obesity, diabetes,
diabetes,
hypertension
hypertension and
hypertension osteoarthritis 81
and osteoarthritis
and osteoarthritis 81
81
.. . However
However
However gender
gender
gender isis
is not
not
not an
an
independent
independent
independentpredictor
predictor
predictorof
ofof111year
year
yearsurvival.
survival.
survival.
9.2.1
9.2.1 Clinical
Clinical
ClinicalPresentation
Presentation
Presentation
Women
Women
Womenpresenting
presenting
presentingwith
with
withACS
ACS
ACSoften
often
oftenhave
have
haveatypical
atypical
atypicalsymptoms
symptoms
symptomssuchsuch
asasneck
neck
neckand
and
andshoulder
shoulder
shoulderache
ache
acheand
and
anddyspnoea.
dyspnoea.
dyspnoea.Often,
Often,
Often,women
women
women havehave
non
nonspecific
specific
specificECG
ECG
ECGchanges
changes
changessuch
such
suchasas
asTTTwave
wave
wavechanges
changes
changeseven
even
eveninin the
the
absence
absence
absenceof ofofheart
heart
heartdisease,
disease,
disease,thus
thus
thusmaking
making
making the
the
the diagnosis
diagnosis
diagnosis ofof
of CAD
CAD
difficult.
difficult.
difficult.
9.2.2
9.2.2
9.2.2 Management
Management
Management
InIngeneral,
general,
general,there
there
thereare
are
areno
no
nogender
gender
genderspecific
specific
specificdifferences
differences
differencesinin
inthe
the
theefficacy
efficacy
efficacy
ofofthe
the
thecommonly
commonly
commonlyusedused
useddrugs
drugs
drugsin
ininACS.
ACS.
ACS.TheThe
Thefollowing
following
following are
are
are some
some
important
important
importantdifferences:
differences:
differences:
I, BI, B Prasugrelis
Prasugrel
Prasugrel isisassociated
associatedwith
associated withmore
with morebleeding
more bleedinginin
bleeding inindividuals
individualswho
individuals who
areless
are
are lessthan
less than60kg
than 60kgin
60kg weight31
ininweight
weight 31
31
.. .
I, BI, B A A meta-analysis
meta-analysis indicates
meta-analysis indicates aaa lack
indicates lack of
lack of benefit
of benefit of
benefit of GPIIb/IIIa
of GPIIb/IIIa
GPIIb/IIIa
inhibitorsin
inhibitors
inhibitors women82
ininwomen
women 8282
.. The
.The
Thebleeding
bleeding
bleedingrisk
risk
riskisisisalso
also
alsohigher.
higher.
higher.
IIa,IIa,
AA Thereis
There
There isisconflicting
conflictingdata
conflicting data regarding
data regarding the
regarding the benefits
the benefits ofof
benefits of anan early
an early
invasivestrategy
invasive
invasive strategyin
strategy ininwomen
womenwith
women UA/NSTEMI66,84-86
withUA/NSTEMI
with UA/NSTEMI 66,84-86
66,84-86
. ..Until
Until
Untilthis
this
issue
issue
issueis
isisresolved
resolved
resolvedin ininrandomized
randomized
randomizedcontrolled
controlled
controlledtrials,
trials,
trials, anan
an invasive
invasive
invasive
strategy
strategy
strategyisisisbest
best
bestreserved
reserved
reservedfor for
forwomen
women
womenwith
with
withongoing
ongoing
ongoingischemia
ischemia
ischemiaand and
raised
raised
raisedtroponins.
troponins.
troponins.
9.3 UA/NSTEMI in Chronic Kidney Disease (CKD)
In patients with ACS, the presence of CKD is an additional high-

35
35
35
risk feature associated with increased mortality, the more severe
87-90
the CKD, the higher the mortality .
The creatinine clearance can be calculated using the Cockroft-

Gault formula (Appendix VI, 34 pg 56). Drug doses should be
I, B
adjusted according to renal function.
9.3 Clinical
UA/NSTEMI in Practice
Chronic KidneyGuidelines
Disease (CKD) on
In patients with ACS, the presence of CKD is an additional high-
risk feature associated with increased mortality, the more severe
the CKD, the higher the mortality.87-90
The creatinine clearance can be calculated using the Cockroft-

Gault formula (Appendix VI, pg 56). Drug doses should be
I, B
adjusted according to renal function.
Patients with renal impairment were excluded from most clinical

trials. In general, the management of patients with CKD is similar
to those with normal renal function except for the following
differences:
Patients with CKD have more co-morbidity.

ACE-I and ARB may cause worsening renal function and
hyperkalemia.
They are at increased bleeding risks. The doses of
antithrombotic agents need to be adjusted accordingly to avoid
excessive bleeding (Table 6, pg 35). Bivalirudin and
I, B
fondaparinux seem to be associated with less bleeding than
heparin or enoxaparin 45,91.
A recent meta-analysis showed that patients with CKD
IIa, B
presenting as UA/NSTEMI and treated with an early invasive
strategy had better outcomes particularly in patients with mild to
moderate renal insufficiency 92,93.
PCI in patients with CKD is associated with increased risks of:
bleeding
worsening renal function and acute on chronic renal failure due
to contrast nephropathy and/or cholesterol embolisation.
Strategies should be taken to reduce this risk. (Appendix VII, pg
56 and VIII, pg 57)
Table 6: Dosages of Anti-thrombotics in CKD*

Table 6: Dosages of Anti-thrombotics in CKD*
LOADING DOSE MAINTENANCE DOSE

LOADING DOSE MAINTENANCE DOSE
UFH No change No change
UFH No change No change
Enoxaprin 30 mg IV 1 mg/kg sc every 24 hours if
Enoxaprin 30 mg IV 1 mg/kg sc every 24 hours if
CrCl < 30 ml/min
CrCl < 30 ml/min
Fondaparinux Avoid if Cr Cl < 30 ml/min Avoid if Cr Cl < 30 ml/min
Fondaparinux Avoid if Cr Cl < 30 ml/min Avoid if Cr Cl < 30 ml/min
Eptifibatide 180 mcg/kg IV Infusion 1.0 mcg/kg/min if
Eptifibatide 180 mcg/kg IV Infusion 1.0 mcg/kg/min if
CrCl
Cr Cl<<5050ml/min
ml/min
Tirofiban IV 36
Tirofiban IV infusion 0.4 mcg/kg/min
infusion 0.4 mcg/kg/min IV IVinfusion
infusion0.05
0.05mcg/kg/min
mcg/kg/min if if
for
for 30
30 mins
mins CrCl
Cr Cl<30
<30ml/min
ml/min
* *Modified
Modifiedfrom
fromACC/AHA
ACC/AHA 2007
2007 Guidelines for the
Guidelines for theManagement
ManagementofofPatients
Patientswith
with UA/NSTEMI.
UA/NSTEMI.
J JAm
AmColl
CollCardiol
Cardiol2007;
2007; 50:1-157.
50:1-157.
9.4
9.4 UA/NSTEMI
UA/NSTEMI in
in Diabetes
Diabetes
94,95
Diabetics
Diabetics have
have an
an increased mortality
mortality
35 followingan
following anACSACS94,95 . The
. The
glucose
glucose level
level at
at admission has been
admission has been shown
shown toto be
beaasignificant
significant
Fondaparinux
Eptifibatide Avoid if Cr Cl < 30 ml/min Avoid
180 mcg/kg if Cr Cl
IV Infusion 1.0<mcg/kg/min
30 ml/min if
Clinical
Eptifibatide Practice Guidelines
180 mcg/kg IV Infusion on
1.0
Cr Cl < 50 ml/minmcg/kg/min if
Tirofiban IV infusion Cr Cl < 50 ml/min
0.4 mcg/kg/minAngina/Non
IV infusion 0.05 mcg/kg/min if
management
Tirofiban IV
of Unstable ST
Elevation Myocardialfor infusion
30 mins0.4Infarction
mcg/kg/min IV Cr infusion 0.05 mcg/kg/min if
Cl <30 ml/min
(UA/NSTEMI) 2011
for 30
* Modified from ACC/AHA mins Cr Cl <30 ml/min
2007 Guidelines for the Management of Patients with UA/NSTEMI.
*J Am
Modified from ACC/AHA
Coll Cardiol 2007 Guidelines for the Management of Patients with UA/NSTEMI.
2007; 50:1-157.
J Am Coll Cardiol 2007; 50:1-157.
9.4 UA/NSTEMI in Diabetes
9.4 UA/NSTEMI in Diabetes
Diabetics have an increased mortality following an ACS 94,95 94,95. The
Diabeticslevel
glucose haveatanadmission
increased has
mortality
been following
shown toanbeACS . The
a significant
glucose level at admission has been shown to be a significant
predictor of 1 year mortality with a predictive value equivalent to LV
predictor of 1 year mortality
systolic dysfunction 96,97
. with a predictive value equivalent to LV
systolic dysfunction 96,97.
Diabetics should be treated aggressively with:
Diabetics should be treated aggressively with:
Antiplatelet agent – aspirin and clopidogrel or prasugrel.
I, B Antiplatelethas
Prasugrel agent
been– aspirin
found toand
be clopidogrel or prasugrel.
more effective in diabetics 31
31.
I, B
IIb, B GP IIb/IIIa inhibitors – a contemporary trial in
Prasugrel has been found to be more effective indicated . a
diabeticsonly
IIb, B GP IIb/IIIa
modest inhibitors
reduction – a contemporary
in adverse events 98,99. trial indicated only a
I, A modest
Early reduction
invasive in adverse
approach events 98,99
– diabetics are. however at higher risk
I, A Early invasive approach – diabetics are however at higher risk
of contrast nephropathy than non diabetics.
of contrast nephropathy than non diabetics.
There is still a lack of consensus on the optimal management of
There sugars
blood is still aduring
lack oftheconsensus on the
acute event. optimalinsulin
Intensive management
therapy of
to
blood sugars
achieve during theinacute
normoglycemia event.
the acute Intensive
setting insulin
has not beentherapy to
shown to
achievemortality
reduce normoglycemia in the acute
and is associated setting
with has not in
an increase been
the shown to
episodes
reduce
of mortality 100
hypoglycemia and is associated with an increase in the episodes
I, B 100. A general consensus is to keep blood sugars
I, B of hypoglycemia
less than 8mmol/l .inA the general
acuteconsensus
setting andis to keep
then aimblood sugars
for optimal
less than
control 8mmol/l
following in the acute setting and then aim for optimal
discharge.
control following discharge.
10. Post Hospital Discharge
10. Post Hospital Discharge
The acute phase of UA/NSTEMI is usually 1 to 3 months. The
The
risk acute phase of of
of recurrence UA/NSTEMI
ischaemic isevents,
usually STEMI
1 to 3 months.
or deathTheis
risk of during
highest recurrence of ischaemic
this period. Followingevents, STEMI
this, most or death
patients assumeis
highest
a clinicalduring thissimilar
course period.toFollowing this, most
that of patients patients
with chronicassume
stable
a clinical course similar to that of patients with chronic stable
angina.
angina.
Several lifestyle modification measures and drug therapies have
Several
been shownlifestyle
to modification
be effective measures and drug
in improving therapies
long-term have
outcome.
been shown to be effective in improving long-term outcome.
However they are underutilized. Therefore37 health care providers
should ensure that patients 37 with UA/NSTEMI receive
appropriate treatment post hospital discharge and ensure that
patients remain compliant to treatment.
Important discharge instructions should include:

education on medication
Patients given sublingual nitrates should be instructed in its
proper and safe use.
lifestyle change and CV risk factors modification
scheduling of timely follow-up appointment and dates for
further investigations
referral to a cardiac rehabilitation program where appropriate
10.1 Medications post-discharge (Table1, pg 4)
10.1.1 Antiplatelet agents

36
I, A ASA should be prescribed at 75-150 mg daily unless
Patients given sublingual nitrates should be instructed in its
Clinical Practice
proper and safe use. Guidelines on
lifestyle change and CV risk factors modification
scheduling of timely follow-up appointment and dates for
further investigations
referral to a cardiac rehabilitation program where appropriate
10.1 Medications post-discharge (Table1, pg 4)
10.1.1 Antiplatelet agents
I, A ASA should be prescribed at 75-150 mg daily unless

contraindicated 26,27.
I, A In patients who cannot tolerate ASA, clopidogrel is an

alternative. It has better risk reduction 101. When clopidopgrel is
not available, ticlopidine can be given.
The combination of ASA and clopidogrel 75 mg daily should be

I, A
continued for at least one month and ideally up to 9 to 12
months after UA/NSTEMI treated medically 71,102 and in patients
who have undergone PCI with bare metal stents.
I, A If patients received drug eluting stents during PCI then dual

antiplatelet treatment is recommended 71,102,103.
The duration of dual antiplatelet therapy following DES

I, C
implantation is for 6 to 12 months or longer 103.
There are no recent clinical trial data on the use of triflusal in

ACS.
10.1.2 β-blockers (see section 7.2.4.2)
I, B β-blockers should be continued for patients with ischemia unless

contraindicated.
I, B Long term treatment following UA/NSTEMI may lead to

significant mortality reduction104.
I, A β-blockers should be continued indefinitely in patients with

38
reduced LV function, with or without symptoms of heart
failure105,106.
10.1.3 Lipid Modifying Therapy
I, A There is a large body of evidence that early initiation of statin

therapy improves outcome regardless of baseline LDL-C
levels in patient with ACS 49-51,07-109.
I, A More aggressive lipid lowering further lowers cardiovascular
event rates 110.
Lipid management includes:

37
I, C Assessment of a fasting lipid profile for all patients, within 24
Clinical
β-blockers Practice
should Guidelines
be continued indefinitely in on
patients with
reduced LV function,
management with or without
of Unstable symptoms ofSTheart
Angina/Non
failure105,106
Elevation .
Myocardial Infarction (UA/NSTEMI) 2011
10.1.3 Lipid Modifying Therapy
I, A There is a large body of evidence that early initiation of statin

therapy improves outcome regardless of baseline LDL-C
levels in patient with ACS 49-51,07-109.
I, A More aggressive lipid lowering further lowers cardiovascular
event rates 110.
Lipid management includes:
I, C Assessment of a fasting lipid profile for all patients, within 24

hours of hospitalization.
I, A Statins, in the absence of contra-indications, regardless of

baseline LDL-C and diet modifications, should be initiated
soon after admission and continue indefinitely to provide life
long benefits 111,112. This also applies to patients post PCI.
I, A LDL-C level should be targeted <2.0 mmol/L for most patients
111,112
.
I, B
Patients with low HDL-C may benefit from fibrates or nicotinic
acid 113,114.
10.1.4 Angiotensin-converting enzymes inhibitors (ACE-Is) (Table

7, pg 39)
I, A
ACE-Is have shown long term benefit in all patients with
evidence of LV dysfunction (LVEF ≤40%) 115-117 and in
patients with diabetes, hypertension or CKD unless
contraindicated 1018-120.
IIa, A For all other patients ACE-Is should be considered to prevent

recurrence of ischaemic events 121-124.
IIa, A
For patients with reduced LV systolic function, ACE-I should
be initiated early, during the course of hospitalization. Agents
and doses of proven efficacy are recommended.
39
38
Table
Table 7:
7: Recommended
Recommended dosages dosages of of ACE-I
ACE-I inin UA/NSTEMI
UA/NSTEMI
Table 7: Recommended dosages of ACE-I in UA/NSTEMI
Type
Type Initiation
Initiation dosedose Target
Target dose
dose
Type Initiation dose Target dose
Captopril
Captopril 6.25 mg bd-tds
6.25 mg bd-tds 25-50
25-50 mg tds
mg tds
Captopril 6.25 mg bd-tds 25-50 mg tds
Ramipril
Ramipril 2.5 mg
2.5 mg bd bd 10 mg
10 mg od od
Ramipril 2.5 mg bd 10 mg od
Enalapril
Enalapril 2.5-5
2.5-5 mg od 20 mg bd
Enalapril 2.5-5 mg mg od od 20
20 mg
mg bdbd
Enalapril 2.5-5 mg od 20 mg bd
Lisinopril
Lisinopril 5
5 mg
mg od
od 40
40 mg
mg od
od
Lisinopril 5 mg od 40 mg od
Lisinopril 5 mg od 40 mg od
Perindopril
Perindopril 2-2.5 mg
2-2.5 mg od od 8-10 mg
8-10 mg od
Perindopril 2-2.5 mg od 8-10 mg od od
Perindopril 2-2.5 mg od 8-10 mg od
10.1.5 Angiotensin-Receptor
10.1.5 Angiotensin-Receptor
Angiotensin-Receptor Blockers Blockers
Blockers (ARBs)(ARBs) (Table
(ARBs) (Table
(Table 8,8, pg
8, pg 39)
pg 39)
39)
10.1.5
10.1.5 Angiotensin-Receptor Blockers (ARBs) (Table 8, pg 39)
I, A ARBs should be substituted for patients with ACE-I
I,
I, AA ARBs
ARBs should
should
125-127 be
be substituted
substituted for for patients
patients withwith ACE-I
ACE-I
I, A intolerance
ARBs should 125-127.
125-127. be substituted for patients with ACE-I
intolerance
intolerance 125-127.
intolerance
Table .
8: Recommended dosages of ARB in UA/NSTEMI
Table
Table 8:8: Recommended
Recommended dosages dosages of of ARB
ARB inin UA/NSTEMI
UA/NSTEMI
Table 8: Recommended
Type dosagesdose
Initiation of ARB in UA/NSTEMI
Target dose
Type
Type Initiation
Initiation dosedose Target
Target dose
dose
Type
Valsartan Initiation
40-80 mg od dose Target
160 mgdoseod
Valsartan
Valsartan 40-80 mg
40-80 mg od od 160
160 mg od
mg od
Valsartan
10.1.6 Aldosterone receptor antagonist 40-80 mg od 160 mg od
10.1.6
10.1.6 Aldosterone
Aldosterone receptor
receptor antagonist
antagonist
10.1.6 Aldosterone receptor antagonist
Long-term aldosterone receptor blockade should be considered
I, B Long-term
I, B in patients aldosterone
Long-term who are inreceptor
aldosterone receptor blockade
blockade
heart failure and should
alreadybe
should considered
betreated
considered
with
I, B Long-term
in patients aldosterone
who receptor blockade should betreated
considered
I, B in patients
ACE-I who are
and β-blockers.are in heart
inThese failure
heartagents and
and already
failureinclude already treated with
spironolactone with
and
in patients who are inThese heartagents
failureinclude
and already treated with
ACE-I and β-blockers.
and spironolactone and
128,129
epleronone
ACE-I β-blockers.
. These agents include spironolactone and
ACE-I and β-blockers.
epleronone 128,129
.. These agents include spironolactone and
epleronone 128,129
128,129
epleronone
Care should be .taken in patients with renal dysfunction and
Care
Care should
should be
hyperkalaemia. be taken
taken in in patients
patients with with renal
renal dysfunction
dysfunction and and
Care should be taken in patients with renal dysfunction and
hyperkalaemia.
hyperkalaemia.
10.1.7 hyperkalaemia.
Anti Anginal Therapy
10.1.7
10.1.7 Anti
Anti Anginal
Anginal Therapy
Therapy
Anti anginals are not required for patients with successful
I, C10.1.7 Anti Anginal Therapy
Anti
Anti anginals
anginals are
revascularization areand not
notno required for
for patients
residual ischaemia.
required patients with
with successful
successful
I,
I, C
C Anti anginals areand
revascularization notno required
residual for patients with successful
ischaemia.
I, C revascularization and no residual ischaemia.
10.2 Follow-up investigations (Fig
revascularization and no residual ischaemia. 1, pg 5)
10.2
10.2 Follow-up
Follow-up investigations (Fig 1, pg 5)
In the outpatient investigations
10.2 Follow-up evaluation of (Fig
investigations low 1,
(Fig
pg UA/NSTEMI
risk
1, pg 5)
5) patients, the
following
In investigations
outpatient maybe
evaluation considered:
In the outpatient evaluation of low risk UA/NSTEMI patients,
the of low risk UA/NSTEMI patients, the the
In the outpatient
following evaluation
investigations maybe of low risk UA/NSTEMI patients, the
considered:
following investigations
Echocardiogram maybe
to assess considered:
LV function
following investigations maybe considered:
Treadmill stress test
Echocardiogram to
Echocardiogram
Stress echocardiogram
to assess
assess LV
LV function
function
– treadmill or pharmacological stress
Echocardiogram
Treadmill
Treadmill stress
stress to assess
test
test LV function
Nuclear
Treadmill
Stress perfusion
stress test
echocardiogram study – treadmill or pharmacological stress
Stress
MRI echocardiogram
– stress MRI for ischaemia– treadmillandorperfusion
pharmacological stress
MRI for viability
Stress
Nuclearechocardiogram
Nuclear perfusion
perfusion studystudy – treadmill or pharmacological stress
MRI –
Nuclear perfusion study 40
MRI – stress
stress MRI
MRI for for ischaemia
ischaemia and and perfusion
perfusion MRI
MRI for
for viability
viability
MRI – stress MRI for ischaemia and 40perfusion MRI for viability
40
39 40
Low risk patients with significant demonstrable ischaemia and all

Low
Low risk
risk patients
patients with significant demonstrable ischaemia andand all
intermediate/high riskwith significant
patients should bedemonstrable
considered forischaemia all
revascularization.
intermediate/high
intermediate/high risk
risk patients
patients should
should be
be considered
considered for
for revascularization.
revascularization.
Key
Key messages
Key messages
messages
Patients
Patients should
should be
be on on optimal
optimal medical
medical therapy
therapy at
at discharge.
discharge. This
This
Patients
includes should
ASA I,A be on optimal medical therapy at discharge. This
I,A, clopidogrel (for at least a month and ideally for
includes
includes ASA I,A, clopidogrel (for at least a month and ideally for
at least
at least aaASA
year) ,I,B
year)
I,Bclopidogrel (for
I,B at least aI,Cmonth and
, β-blockers I,B I,A ideally for
+ CCBs I,C, ACE-I I,A or ARB I,B
I,B, β-blockers I,B + CCBs I,C, ACE-I I,A or ARB I,B
I,B
at
andleast a year)
statins I,A , β-blockers + CCBs , ACE-I or ARB
I,A. (Table 1, pg 4)
and statins I,A. (Table 1, pg 4)
and statins . (Table 1, pg 4)
These
These drugs
drugs should
should be be uptitrated
uptitrated during
during outpatient
outpatient visits
visits to
to the
the
These drugs should
recommended tolerated be doses
uptitrated
I,C. during outpatient visits to the
I,C
recommended tolerated doses I,C.
recommended tolerated doses .
Low
Low risk
risk patients
patients should should bebe assessed
assessed non-invasively
non-invasively for for
Low risk I,C
ischaemia patients
I,C . (Fig 1, should
pg 5) be assessed non-invasively for
ischaemia I,C . (Fig 1, pg 5)
ischaemia . (Fig 1, pg 5)
11. Cardiac Rehabilitation/Secondary prevention

11. Cardiac Rehabilitation/Secondary prevention
Cardiac rehabilitation is aimed at improving the physical and psychological
Cardiac rehabilitation is aimed at improving the physical and psychological
well being of the patient. It has been shown to reduce mortality by
well being of 20%-25%
approximately the patient. It .has
130-132 been
There wasshown
also a to reduce
trend mortality
towards by
reduction
130-132
approximately 20%-25%
in non-fatal recurrent MI over a .median
There was also aoftrend
follow-up towards
12 months 133reduction
.
in non-fatal recurrent MI over a median follow-up of 12 months 133.
11.1 Cardiac rehabilitation programs include:
11.1 Cardiac rehabilitation programs include:
Counselling and educating the patient and family members on CAD
Counselling
Beginning anand educating
exercise the patient and family members on CAD
program
Beginning
Helping theanpatient
exercise program
modify risk factors such as high blood pressure,
Helping thehigh
smoking, patient modify
blood risk factors
cholesterol, such as
physical high blood
inactivity, pressure,
obesity and
smoking, high blood cholesterol, physical inactivity, obesity and
diabetes
diabetes
Providing vocational guidance to enable the patient to return to work
Providing
Supplying vocational
Supplying informationguidance
information on to enable
on physical
physical the patient to return to work
limitations
limitations
Supplying
Educating information
Educating and
and ensuring
ensuringoncompliance
physical limitations
compliance to
to medications
medications
Educating
Providing and ensuring
Providing emotional
emotional compliance to medications
support
support
Providing emotional support
Cardiac
Cardiac rehabilitation/secondary
rehabilitation/secondary prevention
prevention programs
programs are are generally
generally
Cardiacinto
divided
divided rehabilitation/secondary
into 3
3 main
main phases:
phases: prevention programs are generally
divided into 3 main phases:
Phase
Phase 1: 1: Inpatient
Inpatient CR
CR (also
(also known
known as as Phase
Phase 1 1 CR):
CR): aa program
program that
that
Phase
delivers1:preventive
delivers Inpatient CR
preventive and (also
and known as
rehabilitative
rehabilitative Phase to
services
services 1 CR):
to a program
hospitalized
hospitalized that
patients
patients
delivers
followingpreventive
following ACS
ACS and rehabilitative services to hospitalized patients
following ACS
Phase
Phase 2: 2: Early
Early outpatient
outpatient CR
CR (also
(also known
known asas Phase
Phase 2 2 CR):
CR): generally
generally
within
within the
Phase first 3outpatient
first 3 to
2: Early
the to 6
6 months
monthsCRbut continuing
(also
but known as
continuing upPhase
up to
to 1
1 year
2 CR): generally
year
within the first 3 to 6 months but continuing up to 1 year
Phase 3: Long-term outpatient CR (also known as Phase 3 or Phase
41
4 CR): beyond 1 year 41
41
11.2 Return to physical activity 40
Elevation Myocardial
Phase 3: Long-term outpatientInfarction (UA/NSTEMI)
CR (also known 2011
as Phase 3 or Phase
4 CR): beyond 1 year
11.2 Return to physical activity
Physical activity can be resumed at 50% of maximal exercise capacity in a

patient with preserved LV function without inducible ischemia within 1
week post-discharge. This should be gradually increased over time
preferably guided by treadmill stress test.
11.3 Risk factor modification:
Smoking cessation – Patients who quit smoking can reduce the

rate of reinfarction and death as early as 1 year.
Weight – Achieve or maintain optimal body weight.
Exercise – Encourage a minimum of 30–60 minutes of moderate

activity 3-4 times weekly (walking, cycling, swimming or other
equivalent aerobic activities).
Diet – To consume low cholesterol or low saturated fat diet.
Lipids – Aim for an LDL-C < 2.0 mmol/l.
Hypertension – Aim for a blood pressure of <140/85 mmHg. In

diabetics the target is <130/80 mmHg. In elderly patients, a higher
BP target may be acceptable.
Diabetes Mellitus – Optimal glycemic control in diabetes. (Refer

CPG on Diabetes)
11.4 Discharge Instructions
Therapeutic lifestyle changes should be initiated in all patients and

reemphasized during follow up.
Patients should be on optimal medical therapy. (Table 1, pg 4).

They should be educated on the importance of adherence to drug
therapy to ensure optimal outcomes. Patients with DES should be
warned of the consequences of non compliance to anti platelet drug
therapy.
The doses of ACE-I/ARB and β-blockers should be uptitrated to the

maximal tolerated doses.
Patients should be instructed on how to use GTN. If the chest pain

does not subside after 2 GTN’s or if there is a change in the usual
pattern of angina, they should go to the nearest health facility.
42
41
REFERENCES
1. National Cardiovascular Disease Database. NCVD-ACS Registry1st Annual Report

2006, assessed at www.acrm.org.my
2. Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation.
2000; 102 : 118-22.
3. Brieger D, Eagle KA, Goodman SG et al for the GRACE Investigators. Acute
coronary syndromes without chest pain, an underdiagnosed and undertreated
high-risk group: insights from the Global Registry of Acute Coronary Events.
Chest. 2004;126 : 461– 469.
4. Malmberg K, Yusuf S, Gerstein HC et al. Impact of diabetes on long-term
prognosis in patients with unstable angina and non-Q-wave myocardial infarction:
results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes)
Registry. Circulation 2000; 102 : 1014–1019.
5. Al Suwaidi J, Reddan DN, Williams K et al. Prognostic implications of
abnormalities in renal function in patients with acute coronary syndromes.
Circulation 2002; 106 : 974–980.
6. Selker HP, Zalenski RJ, Antman EM, Aufderheide TP. An Evaluation of
Technologies for Identifying Acute Cardiac Ischemia in the Emergency
Department: A Report from a National Heart Attack Alert Program Working Group.
Ann Emerg Med 1997; 29 : 13-87.
7. Kudenchuk PJ, Maynard C, Cobb LA et al for the MITI Investigators.
Utility of the prehospital electrocardiogram in diagnosing acute coronary
syndromes: the Myocardial Infarction Triage and Intervention (MITI) project.
J Am Coll Cardiol 1998; 32 : 17-27
8. Langer A, Freeman MR, Armstrong PW. ST segment shift in unstable angina:
pathophysiology and association with coronary anatomy and hospital outcome. J
Am Coll Cardiol 1989; 13 : 1495-1502
9. Cannon CP, McCabe CH, Stone PH et al.The electrocardiogram predicts one-year
outcome of patients with unstable angina and non-Q wave myocardial infarction:
results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial
Ischemia.J Am Coll Cardiol 1997; 30 : 133-140
10. Savonitto S; Ardissino D; Granger CB et al. Prognostic Value of the Admission
Electrocardiogram in Acute Coronary Syndromes.JAMA. 1999; 281 : 707-713.
11. Hyde TA, French JK, Wong C-K et al. Four-year survival of patients with acute
coronary syndromes without ST-segment elevation and prognostic significance of
0.5-mm ST-segment depression. Am J Cardiol 1999; 8 : 379-385
12. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac troponin T levels for
risk stratification in acute myocardial ischemia. GUSTO IIA Investigators. N Engl J
Med 1996; 335 : 1333-41.
13. Stubbs P, Collinson P, Moseley D et al. Prognostic significance of admission
troponin T concentrations in patients with myocardial infarction. Circulation 1996;
94:1291-7.
14. Lindahl B, Toss H, Siegbahn A et al. Markers of myocardial damage and
inflammation in relation to long-term mortality in unstable coronary artery disease.
FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl
J Med 2000; 343 : 1139-47.
15. Newby LK, Christenson RH, Ohman EM, et al. Value of serial troponin T
measures for early and late risk stratification in patients with acute coronary
syndromes. The GUSTO-IIa Investigators. Circulation 1998; 98 : 1853-9.
44
42
16. Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of
subsequent cardiac events in unstable coronary artery disease. The FRISC study
group. Circulation 1996; 93 : 1651-7
17. Thygesen K, Mair J,Katus H et al for Study Group on Biomarkers in Cardiology of
the ESC Working Group on Acute Cardiac Care. Recommendations for the use of
cardiac troponin measurement in acute cardiac care. Eur Heart J 2010; 31 : 2197-
2204.
18. Newby LK, Roe MT, Chen AY, et al. Frequency and clinical implications of
discordant creatine kinase-MB and troponin measurements in acute coronary
syndromes. J Am Coll Cardiol 2006; 47 : 312-8.
19. Goodman SG, Steg PG, Eagle KA, et al. The diagnostic and prognostic impact of
the redefinition of acute myocardial infarction: lessons from the Global Registry of
Acute Coronary Events (GRACE). Am Heart J 2006; 151 : 654-60.
20. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable
angina/non-ST elevation MI: a method for prognostication and therapeutic
decision making. JAMA 2000; 284 : 835–42 .
21. Sabatine MS, Morrow DA, Giugliano RP, et al. Implications of upstream
glycoprotein IIb/IIIa inhibition and coronary artery stenting in the invasive
management of unstable angina/non ST elevation myocardial infarction. A
comparison of the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial and the
Treat angina with Aggrastat and determine Cost of Therapy with Invasive or
Conservative Strategy (TACTICS)-TIMI 18 trial. Circulation 2004; 109 : 874-880.
22. Eagle KA, Lim MJ, Dabbous OH et al. for the GRACE investigators. A validated
prediction model for all forms of acute coronary syndrome. Estimating the risk of 6-
month postdischarge death in an international registry. JAMA 2004; 291 : 2727–
2733.
23. Goncalves PD, Ferreira J,Aguiar C,Seabra Gomes R. TIMI, PURSUIT, and
GRACE risk scores: sustained prognostic value and interaction with
revascularization in NSTE-ACS. Eur Heart J 2005; 26 : 865-872.
24. Mehran R, Pocock SJ,Nikolsky E et al . A Risk Score to Predict Bleeding in
Patients With Acute Coronary Syndromes. J Am Coll Cardiol 2010; 55 : 2556-
2566.
25. Subherwal S, Bach RG,Chen AY et al. Baseline Risk of Major Bleeding in Non–
ST-Segment–Elevation Myocardial Infarction.The CRUSADE (Can Rapid risk
stratification of Unstable angina patients Suppress ADverse outcomes with Early
implementation of the ACC/AHA guidelines) Bleeding Score. Circulation. 2009;119
: 1873-1882
26. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised
trials of antiplatelet therapy for prevention of death, myocardial infarction, and
stroke in high-risk patients. Br Med J 2002; 324 : 71-86.
27. The CURRENT-OASIS Investigators. Dose comparisons of clopidogrel and aspirin
in acute coronary syndromes. N Engl J Med 2010; 363 : 930-942.
28. Lotrionte M, Biondi-Zoccai GGL, Agostino P et al. Meta-Analysis Appraising High
Clopidogrel Loading in Patients Undergoing Percutaneous Coronary Intervention.
Am J Cardiol 2007; 100 : 1199-1206
29. Kandzari DE, Berger PB, Kastrati A et al. ISAR-REACT Study Investigators
Influence of treatment duration with a 600-mg dose of clopidogrel before
percutaneous coronary revascularization. J Am Coll Cardiol 2004; 44 : 2133–
2136.
30. Bennett JS.: Novel platelet inhibitors. Annu. Rev Med 2001; 52 : 161
31. Montalescot G, Wiviott SD, Braunwald E et al for the TRITON-TIMI 38
Investigators. Prasugrel compared with clopidogrel in patients undergoing
percutaneous coronary intervention for ST –elevation myocardial infarction
45
43
(TRITON-TIMI 38): double blind, randomized controlled trial. Lancet 2009; 373 :
723-731.
32. Wallentin L, Becker RC, Budaj A et al. for the PLATO Investigators. Ticagrelor
versus Clopidogrel in Patients with Acute Coronary Syndromes.N Engl J Med
2009; 361 : 1045-1057.
33. Giugliano RP, White JA, Bode C, et al., on behalf of the EARLY ACS
Investigators. Early versus delayed, provisional eptifibatide in acute coronary
syndromes. N Engl J Med 2009; 360 : 2176-2190
34. Stone GW, Ware JH, Betrand ME et al for the ACUITY Investigators.
Antithrombotic strategies in patients with acute coronary syndromes undergoing
early invasive management: one-year results from the ACUITY trial. JAMA 2007;
298 : 2497-2506.
35. Cohen M, Demers C, Gurfinkel EP et al. A comparison of low-molecular-weight
heparin with unfractionated heparin for unstable coronary artery disease. Efficacy
and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study
Group. N Engl J Med 1997; 337 : 447-52.
36. Antman EM, McCabe CH, Gurfinkel EP et al. Enoxaparin prevents death and
cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction.
Results of the thrombolysis in myocardial infarction (TIMI) 11B
trial. Circulation 1999; 100 : 1593-601.
37. Antman EM, Cohen M, Radley D et al. Assessment of the treatment effect of
enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-
ESSENCE meta-analysis. Circulation 1999;100:1602-08.
38. Mehta S, Granger C , Eikelboom J et.al. Efficacy and Safety of Fondaparinux
Versus Enoxaparin in Patients With Acute Coronary Syndromes Undergoing
Percutaneous Coronary Intervention. Results From the OASIS-5 Trial. J Am Coll
Cardiol 2007; 50 : 1742-1751.
39. Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and
reinfarction in patients with acute ST-segment elevation myocardial infarction: the
OASIS-6 randomized trial. JAMA 2006; 295 : 1519–30.
40. Mehta SR, Boden WE, Eikelboom JW, et al., on behalf of the OASIS 5 and 6
Investigators Antithrombotic Therapy With Fondaparinux in Relation to
Interventional Management Strategy in Patients With ST- and Non-ST-Segment
Elevation Acute Coronary Syndromes. An Individual Patient-Level Combined
Analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic
Syndromes (OASIS 5 and 6) Randomized Trials. Circulation 2008; 118 : 2038-
2046.
41. Gurbuz AT, Elliot WG, Zia AA. Heparin-induced thrombocytopenia in the
cardiovascular patient: diagnostic and treatment guidelines. Eur J Cardiothorac
Surg 2005; 27 : 138-149.
42. Kastrati A, Neumann F-J, Mehilli J, et al. ISAR-REACT 3 Trial Investigators
Bivalirudin versus unfractionated heparin during percutaneous coronary
intervention. N Engl J Med 2008; 359 : 688-696.
43. Lincoff AM, Bitti JA, Harrington RA for the REPLACE-2 Investigators.
Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events
(REPLACE 2). JAMA 2003; 289 : 853-863.
44. Stone GW, Ware JH, Betrand ME et al for the ACUITY Investigators.
Antithrombotic strategies in patients with acute coronary syndromes undergoing
early invasive management: one-year results from the ACUITY trial. JAMA 2007;
298 : 2497-2506.
45. Stone GW, Witzenbichler B, Guagliumi G et al for the HORIZONS-AMI Trial
Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl
J Med 2008; 358 : 2218–2230.
46
44
46. Figueras J, Lidon R, Cortadellas J. Rebound myocardial ischaemia following

abrupt interruption of intravenous nitroglycerin infusion in patients with unstable
angina at rest. Eur Heart J 1991; 12 : 405 - 11.
47. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable
Angina/Non–ST-Elevation Myocardial Infarction: A Report of the American College
of Cardiology/American Heart Association Task Force on Practice Guidelines
(Writing Committee to Revise the 2002 Guidelines for the Management of Patients
With Unstable Angina/Non–ST-Elevation Myocardial Infarction). J Am Coll Cardiol
2007; 50 : 652-726.
48. Yusuf S, Held P, Furberg C. Update of effects of calcium antagonist in MI or
angina in light of DAVIT-II and other recent studies. Am J Cardiol 1991; 67 : 1295-
7
49. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid
lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350 :
1495–504.
50. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early
recurrent ischemic events in acute coronary syndromes: The MIRACL study: a
randomized controlled trial. JAMA 2001; 285 : 1711–8.
51. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed
conservative simvastatin strategy in patients with acute coronary syndromes.
JAMA 2004; 292 : 1307–16
52. Ray KK, Cannon CP, McCabe CH, et al. Early and late benefits ofhigh-dose
atorvastatin in patients with acute coronary syndromes. Results from the PROVE
IT-TIMI 22 trial. J Am Coll Cardiol 2005 ; 46 : 1405–10.
53. Hiro T, Kimura T, Morimoto T et al. Effect of Intensive Statin Therapy on
Regression of Coronary Atherosclerosis in Patients With Acute Coronary
Syndrome: A Multicenter Randomized Trial Evaluated by Volumetric Intravascular
Ultrasound Using Pitavastatin Versus Atorvastatin. J Am Coll Cardiol 2009; 54 :
293–302
54. Gibson CM, Pride YB, Hochberg CP et al.Effect of Intensive Statin Therapy on
Clinical Outcomes Among Patients Undergoing Percutaneous Coronary
Intervention for Acute Coronary Syndrome. PCI-PROVE IT: A PROVE IT–TIMI 22
(Pravastatin or Atorvastatin Evaluation and Infection Therapy– Thrombolysis In
Myocardial Infarction 22) Substudy. J Am Coll Cardiol 2009; 54 : 2290–5
55. Yun KH, Oh SK, Rhee SJ et al. 12 month follow up results of high dose
rosuvastatin loading before percutaneous coronary intervention in patients with
acute coronary syndrome. Int J Cardiol 2010 May 14 (E pub ahead of print); doi 10
1016/j.ijcard.2010.04.052
56. Di Sciasco G, Pattio G, Pasceri V et al.Efficacy of atorvastatin reloadin patients on
chronic statin therapy undergoing percutaneous coronary intervention: results of
the the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage
During Angioplasty) Randomised Trial. J Am Coll Cardiol 2009; 54 : 558-565.
57. ACEInhibitor Myocardial Infarction Collaborative Group. Indications for ACE
inhibitors in the early treatment of acute myocardial infarction: systematic overview
of individual data from 100,000 patients in randomized trials. Circulation 1998; 97 :
2202-2212.
58. Theroux P. Thrombosis in coronary artery disease: its pathosiology and control.
Dialogues Cardiovas Med 2002; 7 : 3-18
59. TIMI IIIB Investigators. Effects of tissue plasminogen activator and a comparison
of early invasive and conservative strategies in unstable angina and non-Q-wave
myocardial infarction: results of the TIMI IIIB trial. Thrombolysis in myocardial
Ischaemia. Circulation 1994; 89 : 1545-56
47
45
60. Wallentin L, Lagerqvist B, Husted S et al. Outcome at one year after an invasive
compared with a non-invasive strategy in unstable coronary artery disease: the
FRISC II invasive randomized trial. Lancet 2000; 356 : 9-16.
61. Cannon CP, Weintraub WS, Demopouluos LA et al. Comparison of early invasive
and conservative strategies in patients with unstable coronary syndromes treated
with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001; 344 : 1879-87.
62. Fox KA, Poole- Wilson P, Clayton TC et al. 5-year outcome of an interventional
strategy in non-ST-elevation acute coronary syndrome: the British Heart
Foundation RITA 3 randomised trial. Lancet 2005; 366 : 914-20.
63. Mehta SR, Cannon CP, Fox KA et al. Routine versus selective invasive strategies
in patients with acute coronary syndromes: a collaborative meta-analysis of
randomized trials. JAMA 2005; 293 : 2908-17.
64. Neumann FJ, Kastrati A, Pogatsa-Murray G et al. Evaluation of prolonged
antithrombotic pretreatment (“cooling-off” strategy) before intervention in patients
with unstable coronary syndromes: a randomized controlled trial. JAMA 2003; 290
: 1593-9.
65. de Winter RJ , Windhausen F, Cornel JH et al. Early invasive versus selectively
invasive management for acute coronary syndromes. N Engl J Med 2005; 353 :
1095-104.
66. Bavry AA, Kumbhani DJ, Rassi A, Bhatt DL, Askari AT. Benefit of early invasive
therapy in acute coronary syndromes: a meta-analysis of contemporary
randomized clinical trials. J Am Coll Cardiol 2006; 48 : 1319-25.
67. Hoening MR, Doust J, Aroney CN, Scott IA. Early invasive versus conservative
strategies for unstable angina & non- ST-elevation myocardial infarction in the
stent era. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No:
CD004815. DOI: 10.1002/ 14651858. CD004815.pub2.
68. 0’Donoghue M, Boden WE, Braunwald E et al. Early invasive versus conservative
treatment strategies in women and men with unstable angina and non-ST
segment elevation myocardial infarction. A meta-analysis. JAMA 2008; 300 : 71-
80.
69. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van
De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA; Global Registry of
Acute Coronary Events Investigators. Predictors of hospital mortality in the Global
Registry of Acute Coronary Events. Arch Intern Med. 2003; 163 : 2345–2353.
70. Alexander KP, Newby LK, Cannon CP et al. Ohman EM, Chair Acute Coronary
Care in the Elderly, Part I. Non–ST-Segment–Elevation Acute Coronary
Syndromes: A Scientific Statement for Healthcare Professionals From the
American Heart Association Council on Clinical Cardiology: In Collaboration With
the Society of Geriatric Cardiology .Circulation 2007; 115 : 2549-2569.
71. Brieger D, Eagle KA, Goodman SG et al for the GRACE Investigators. Acute
coronary syndromes without chest pain, an underdiagnosed and undertreated
high-risk group: insights from the Global Registry of Acute Coronary
Events. Chest. 2004; 126 : 461–469
72. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of
antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by
prolonged antiplatelet therapy in various categories of patients [published
correction appears in Br Med J. 1994;308:1540]. BMJ. 1994; 308 : 81–106
73. Budaj A, Yusuf S, Mehta SR et al. Clopidogrel in Unstable angina to prevent
Recurrent Events (CURE) Trial Investigators. Benefit of clopidogrel in patients with
acute coronary syndromes without ST-segment elevation in various risk groups.
Circulation. 2002; 106 : 1622–1626
74. Cohen M, Antman EM, Gurfinkel EP,Radley D. Enoxaparin in unstable angina/non
ST segment elevation MI: treatment benefits in prespecified subgroups. J Thromb
Thrombolysis 2001; 12 : 199-206.
48
46
75. Blankenship JC. Bleeding complications of glycoprotein IIb-IIIa receptor inhibitors.

Am Heart J. 1999; 138 (pt 2): S287–S296
76. Boersma E, Harrington RA, Moliterno DJ et al. Platelet glycoprotein IIb/IIIa
inhibitors in acute coronary syndromes: a meta –analysis of all major randomized
clinical trials. Lancet 2002; 359 : 189-198.
77. Bach RG, Cannon CP, Weintraub WS et al. The effect of routine, early invasive
management on outcome for elderly patients with non-ST-segment elevation
acute coronary syndromes. Ann Intern Med 2004; 141: 186–195
78. FRagmin and Fast Revascularization during InStability in Coronary artery disease
(FRISC II) Investigators. Long-term low-molecular-mass heparin in unstable
coronary artery disease: FRISC II prospective randomised multicentre study
[published correction appears in Lancet 1999;354:1478]. Lancet 1999; 354 : 701–
707
79. Lagerqvist B, Husted S, Kontny F et al. Fast Revascularization during InStability in
Coronary artery disease-II Investigators. A long-term perspective on the protective
effects of an early invasive strategy in unstable coronary artery disease: two-year
follow-up of the FRISC-II invasive study. J Am Coll Cardiol 2002; 40 : 1902–1914
80. Fox KA, Poole-Wilson P, Clayton TC et al. 5-Year outcome of an interventional
strategy in non-ST-elevation acute coronary syndrome: the British Heart
Foundation RITA3 randomised trial. Lancet 2005; 366 : 914–920
81. Cannon CP, Weintraub WS, Demopoulos LA, et al. TACTICS (Treat Angina with
Aggrastat and Determine Cost of Therapy with an Invasive or Conservative
Strategy)–Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of
early invasive and conservative strategies in patients with unstable coronary
syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med
2001; 344 : 1879–1887
82. Derlin G, Gore JM, Elliot J et al for the GRACE Investigators. Management of 6
month outcomes in elderly and very elderly patients with high risk non ST
elevation acute coronary syndromes: the Global Registry of Acute Coronary
Events. Eur Heart J 2008; 29 : 1275-1282.
83. Lerner DJ. Kannel WB. Patterns of coronary heart disease morbidity and mortality
in the sexes: a 26 year follow up of the Framingham population. Am Heart J 1986;
111 : 383-90
84. Boersma E, Harrington RA, Moliterno DJ et al. Platelet glycoprotein IIb/IIIa
inhibitors in acute coronary syndromes: a meta –analysis of all major randomized
clinical trials. Lancet 2002; 359 : 189-198.
85. Fox KA, Poole-Wilson PA, Henderson RA et al. Interventional versus
conservative treatment for patients with unstable angina or non-ST-elevation
myocardial infarction: the British Heart Foundation RITA 3 randomised trial.
Randomized Intervention Trial of unstable Angina. Lancet 2002; 360 : 743-751
86. Wallentin L, Lagerqvist B, Husted S et al. Outcome at 1 year after an invasive
compared with a non-invasive strategy in unstable coronary-artery disease: the
FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation
during Instability in Coronary artery disease. Lancet 2000; 356 : 9-16.
87. Lagerqvist B, Husted S, Kontny F et al. 5-year outcomes in the FRISC-II
randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation
acute coronary syndrome: a follow-up study. Lancet 2006; 368 : 998-1004
88. Hoenig MR, Doust JA, Aroney CN, Scott IA. Early invasive versus conservative
strategies for unstable angina & non-ST-elevation myocardial infarction in the
stent era. Cochrane Database Syst Rev 2006; 3 : CD004815
89. Santopinto JJ,Fox KA, Goldberg RJ, Budaj A, Pinero G, Avezum A, Gulba D,
Esteban J, Gore JM, Johnson J, Gurfinkel EP. Creatinine clearance and adverse
hospital outcomes in patients with acute coronary syndromes: findings from the
global registry of acute coronary events (GRACE). Heart 2003; 89 : 1003-1008.
49
47
90. Best PJ, Lennon R, Ting HH et al. The impact of renal insufficency on clinical
outcomes in patients undergoing percutaneous coronary intervention. J Am Coll
Cardiol 2002; 39 : 1113-9.
91. Reinecke H, Trey T, Matzkies F et al. Grade of chronic renal failure and acute and
long term outcome after percutaneous coronary intervention. Kidney Int 2003; 63 :
696-70.
92. Herzog CA, Ma JZ, Collins AJ. Comparative survival of dialysis patients in the
United States after coronary angioplasty, coronary artery stenting and coronary
artery bypass surgery and the impact of diabetes. Circulation 2002; 106 : 2207-11.
93. Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy
and safety of fondaparinux relative to enoxaparin in non ST-segment elevation
acute coronary syndromes. Ann Intern Med 2007; 147 : 304-310.
94. David M. Charytan, Lars Wallentin, Bo Lagerqvist, Rudolf Spacek, Robbert J. De
Winter, Noam M. Stern, Eugene Braunwald, Christopher P. Cannon, and Niteesh
K. Choudhry. Early Angiography in Patients with Chronic Kidney Disease: A
Collaborative Systematic Review. Clin J Am Soc Nephrol 2009; 4: 1032-1043.
95. Szummer K, Lundman P, Jacobsen SH et al. Influence of renal function on the
effects of early revascularization in non ST elevation myocardial infarction: Data
from the Swedish Web-system for Enhancement and Development of Evidence
based care in Heart Disease Evaluated According to Recommended Therapies. (
SWEDEHEART) Circulation 2009; 120 : 851-858.
96. Kristen Franklin; Robert J. Goldberg; Frederick Spencer; Werner Klein; Andrzej
Budaj; David Brieger; Michel Marre; Philippe Gabriel Steg; Neelam Gowda; Joel
M. Gore; for the GRACE Investigators. Implications of Diabetes in Patients With
Acute Coronary Syndromes: The Global Registry of Acute Coronary Events. Arch
Intern Med 2004; 164 :1457-1463.
97. Donahoe SM, Stewart GC, McCabe CH, et al. Diabetes and mortality following
acute coronary syndromes. JAMA 2007; 298 : 765-775
98. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycemia and
increased risk of death after myocardial infarction in patients with and without
diabetes: a systemic review. Lancet 2000; 355 : 773-778.
99. Monteiro, Sílvia; António, Natália; Gonçalves, Francisco; Monteiro, Pedro; Freitas,
Mário; Providência, Luís A. Glycemia ta samission: the metabolic
echocardiography in acute coronary patients.Eur J of Cardiovas Prev Rehab
2009; 16 : 164-168.
100. Roffi M, Chew DP, Mukherjee D et al. Platelet Glycoprotein IIb/IIIa Inhibitors
Reduce Mortality in Diabetic Patients With Non–ST-Segment-Elevation Acute
Coronary Syndromes. Circulation 2001; 104 : 2767-2771
101. Kastrati A, Mehilli J, Neumann F-J et al for the Intracoronary Stenting and
Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 (ISAR-
REACT 2) Trial Investigators. Abciximab in Patients With Acute Coronary
Syndromes Undergoing Percutaneous Coronary Intervention After Clopidogrel
Pretreatment: The ISAR-REACT 2 Randomized Trial JAMA. 2006; 295 : 1531-
1538
102. SR, Chrolavicius S, Tognoni G, Fox KK. Effects of Clopidogrel in addition
Griesdale DEG, de Souza RJ, van Dam RM et al Intensive insulin therapy and
mortality among critically ill patients: a meta-analysis including NICE-SUGAR
study data. Cand Med Assoc J 2009; 180 : 821-827.
103. CAPRIE Steering Committee; A randomized blinded trial of clopidogrel versus
aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 : 1329-
1339.
104. Yusuf S, Zhao F, Mehta to aspirin in patients with acute coronary syndrome
without ST-segment elevation. N Eng J Med 2001; 345 : 494-502
50
48
105. Grines CL, Bonow RO, Casey Jr DE et al. Prevention of Premature

Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery
Stents. A Science Advisory From the American Heart Association, American
College of Cardiology, Society for Cardiovascular Angiography and Interventions,
American College of Surgeons, and American Dental Association, With
Representation From the American College of Physicians. J Am Coll Cardiol
2007; 49 : 734-739.
106. Lopez-Sendon J, Swedberg K, McMurray Jet al. Expert consensus document on
beta-andrenergic receptor blockers. Eur Heart J 2004; 25 : 1341-1362
107. Dargie HJ. Effects of carvedilol on outcome after myocardial infarction in patients
with left-ventricular dysfunction; the CAPRICORN randomized trial. Lancet 2001;
357 : 1385-90
108. Ellis K, Tcheng JE, Sapp S et al. Mortality benefit of beta blockade in patients with
acute coronary syndromes undergoing intervention; pool results from the Epic,
Epilog, Epistent, Capture and Rapport Trials. J. Interv Cardiol 2003; 16 : 299-305
109. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in
20,536 high risk individuals: a randomized placebo-controlled trial. Lancet 2002;
360 : 7-22.
110. Briel M, Schwartz GG, Thompson PL, et al. Effects of early treatment with statins
on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of
randomized controlled trials. JAMA 2006; 295 : 2046-56
111. Hulten E, Jackson JL, Douglas K et al. The effect of early, intensive statin therapy
on acute coronary syndrome: a meta-analysis of randomized controlled trials.
Arch Intern Med 2006; 166 : 1814-1821
112. De Backer G, Ambrosioni E, Borch-Johnsen K et al. European guidelines on
cardiovascular disease prevention on clinical practice. Third Joint Task Force of
European and Other Societies on Cardiovascular Disease Prevention in Clinical
Practice. Eur Heart J. 2003; 24 : 1601-1610
113. Smith SC Jr, Allen J, Blair SN et al. AHA/ACC guidelines for secondary prevention
for patients with coronary and other atherosclerotic vascular disease 2006 update:
endorsed by the National Heart, lung, and Blood Institute. Circulation 2006; 113 :
2363-2372
114. Ridker PM, Cannon CP, Morrow D et al C Reactive protein levels and outcomes
after statin therapy. N Engl J Med 2005; 352 : 20-28
115. Chapman MJ, Assmann G, Fruchant JC et al. Raising high-density lipoprotein
cholesterol with reduction of cardiovascular risk: the role of nicotinic acid-a
position paper developed by the European Consensus Panel on HDL-C. Curr Med
Res Opin 2004; 20 : 1253-1268
116. Rubins HB, Robins SJ. Collins D et al. Gemfibrazil for the secondary prevention of
coronary heart disease in men with low level of high density lipoprotein
cholesterol. Veteran Affairs HDL cholesterol intervention (VA-HIT) Study Group.
N Eng J.Med 1993; 341 : 410-418
117. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of
ramipril on mortality and morbidity of survivors of acute myocardial infarction with
clinical evidence of heart failure. Lancet 1993; 342 : 821-828
118. Pfeffer MA, Braunwald E, Moye LA et al. on behalf of the SAVE Investigators.
Effect of captopril on mortality and morbidity in patients with left ventricular
dysfunction after myocardial infarction. Results of survival and ventricular
enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327 : 669-677
119. Torp-Pedersen C, Kober L. Effect of ACE inhibitor trandolapril on life expectancy
of patients with reduced left-ventricular function after acute myocardial infarction.
TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet 1999; 354 : 9-12
120. Braunwald E, Domanski MJ, Fowler SE et al. Angiotensin-converting-enzyme
inhibition in stable coronary artery disease. N Engl J Med 2004; 351 : 2058-2068
51
49
121. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among

patients with stable coronary artery disease: randomized, double blind, placebo-
controlled, multicentre trial (the EUROPA study). Lancet 2003; 362 : 782-788
122. Yusuf S, Sleight P, Pogue J et al. Effects on an angiotensin-converting-enzyme
inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart
Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342 :
145-153
123. Dagenais GR, Pogue J, Fox K et al. Angiotensin-converting-enzyme inhibitors in
stable vascular disease without left ventricular systolic dysfunction or heart failure:
a combined analysis of three trials. Lancet 2006; 368 : 581-588
124. Danchin N, Cucherat M, Thuillez C et al. Angiotensin-converting-enzyme inhibitors
in patients with coronary artery disease and absence of heart failure or left
ventricular systolic dysfunction: an overview of long-term randomized controlled
trials. Arch Intern Med 2006; 166 : 787-796
125. Fox K, Ferrari R, Yusuf S, Borer JS. Should angiotensin-converting-enzyme-
inhibitors be used to improved outcome in patients with coronary artery disease
and ‘preserved’ left ventricular function? Eur Heart J 2006; 27 : 2154-2157
126. Pitt B. ACE inhibitors for patients with vascular disease without left ventricular
dysfunction-may they rest in PEACE? N Engl J Med 2004; 351: 2115-7
127. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and
morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL
randomized trial. Optimal Trial in Myocardial Infarction with Angiotensin II
Antogonist Losartan. Lancet 2002; 360 : 752-760
128. Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan, captopril, or both in
myocardial infarction complicated by heart failure, left ventricular dysfunction, or
both. N Engl J Med 2003; 349 : 1893-1906
129. Effect of the angiotensin-receptor blocker telmisartan on cardiovascular events in
high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a
randomized controlled trial: The Telmisartan Randomized Assessment Study in
ACE intolerant subjects with cardiovascular Disease (TRANSCEND)
Investigators. Lancet 2008; 372 : 1174-1183.
130. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and
mortality in patients with severe heart failure. Randomized Aldactone Evaluation
Study Investigators. N Engl J Med 1999; 341: 709-717
131. Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in
patients with left ventricular dysfunction after myocardial infarction. N Engl J Med
2003; 348 : 1309-1321
132. Oldridge NB, Guyatt GH, Fischer ME, Rimm AA. Cardiac rehabilitation after
myocardial infarctionCombined experience of randomized clinical trials. JAMA
1988; 260 : 945-950.
133. O'Connor GT, Buring JE, Yusuf S, et al. An overview of randomized trials of
rehabilitation with exercise after myocardial infarction. Circulation 1989; 80 : 234-
244.
134. McAlister FA, Lawson FM, Teo KK, Armstrong PW. Randomised trials of
secondary prevention programmes in coronary heart disease: systematic review
Br Med J 2001; 323 : 957-962
135. Clark AM, Hartling L, Vandermeer B, McAlister FA. Meta-analysis: secondary
prevention programs for patients with coronary artery disease Ann Intern Med
2005; 143 : 659-672
52
50
APPENDIX I: Braunwald’s Classification of Unstable Angina*
CLINICAL CIRCUMSTANCES
A B C
Severity Develops in Develops in Develops

Presence of Absence of Within 2 weeks
Extracardiac Extracardiac of MI
Condition That Condition (Primary (Postinfarction
Intensifies UA) UA)
Myocardial
Ischemia
(Secondary UA)
I—New onset of
severe angina or
accelerated IA IB IC
angina; no rest
pain
II—Angina at rest
within past month
but not within
preceding 48 hours IIA IIB IIC
(angina at rest,
subacute)
III—Angina at rest
within 48 hours
(angina at rest, IIIA IIIB-Tneg IIIB-Tpos IIIC
acute)
UA : Unstable angina; T : Troponins
*Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation.

2000 ;102 :118-22.
53
51
Appendix
Appendix II:II:Elevations
Elevationsof
of cardiac
cardiac troponin
troponinininthe absence
the of of
absence
overt ischaemic
overt ischaemic heart
heartdisease*
disease*
Damage
Damage related
related to to secondarymyocardial
secondary myocardial ischaemia
ischaemia(MI
(MItype 2) 2)
type
Tachy- or bradyarrhythmias
Tachy- or bradyarrhythmias
Aortic dissection and severe aortic valve disease
Aortic dissection and severe aortic valve disease
Hypo- or hypertension, e.g. haemorrhagic shock, hypertensive emergency
Hypo- or hypertension, e.g. haemorrhagic shock, hypertensive emergency
Acute and chronic heart failure without significant concomitant coronary artery
Acute and chronic
disease (CAD) heart failure without significant concomitant coronary artery
disease (CAD) cardiomyopathy
Hypertrophic
Hypertrophic cardiomyopathy
Coronary vasculitis, e.g. systemic lupus erythematosus, Kawasaki syndrome
Coronary vasculitis,
Coronary e.g.dysfunction
endothelial systemic without
lupus erythematosus,
significant CAD, Kawasaki
e.g. cocainesyndrome
abuse
Coronary endothelial dysfunction without significant CAD, e.g. cocaine abuse
Damage not related to myocardial ischaemia
Damage not related to myocardial ischaemia
Cardiac contusion
Cardiac
Cardiac incisions with surgery
contusion
Radiofrequency or cryoablation
Cardiac incisions with surgery therapy
Rhabdomyolysis with cardiac involvement
Radiofrequency or cryoablation therapy
Myocarditis
Rhabdomyolysis with cardiac involvement
Cardiotoxic agents, e.g. anthracyclines, herceptin, carbon monoxide poisoning
Myocarditis
Severe burns affecting >30% of body surface
Cardiotoxic agents, e.g. anthracyclines, herceptin, carbon monoxide poisoning
Severe burns affecting >30% of body surface
Indeterminant or multifactorial group
Indeterminant or multifactorial
Apical ballooning syndrome group
Severe pulmonary embolism or pulmonary hypertension
Apical ballooning
Peripartum syndrome
cardiomyopathy
Severe
Renal pulmonary
failure embolism or pulmonary hypertension
Severe acute
Peripartum neurological diseases, e.g. stroke, trauma
cardiomyopathy
RenalInfiltrative
failure diseases, e.g. amyloidosis, sarcoidosis
Extreme
Severe acute exertion
neurological diseases, e.g. stroke, trauma
Sepsis
Infiltrative diseases, e.g. amyloidosis, sarcoidosis
Acute respiratory failure
Extreme exertion
Frequent defibrillator shocks
Sepsis
Acute respiratory failure
*Thygesen
Frequent K, Mair J,Katus
defibrillator H et al for Study Group on Biomarkers in Cardiology of the ESC
shocks
Working Group on Acute Cardiac Care. Recommendations for the use of cardiac troponin
measurement in acute cardiac care. Eur Heart J 2010; 31 : 2197-2204.
54
*Thygesen K, Mair J,Katus H et al for Study Group on Biomarkers in Cardiology of the ESC
Working Group on Acute Cardiac Care. Recommendations for the use of cardiac troponin
measurement in acute cardiac care. Eur Heart J 2010; 31 : 2197-2204.
54
52
Appendix
AppendixIII:
III: Likelihood
Likelihood That
That Signs and Symptoms
SymptomsRepresent
Representan
anACS
ACS
secondary
secondary to CAD
CAD
Greater
GreaterLikelihood
Likelihood Lower Likelihood
Lower Likelihood
History
History
Chest
Chestororleft
leftarm
armpain
pain or
or discomfort
discomfort as Chest pains
Chest painsininthe
theabsence
absenceofof
chief
chiefsymptom
symptomreproducing
reproducing prior
prior any of
any of the
the greater
greaterlikelihood
likelihood
documented
documentedangina
angina characteristics
characteristics
Known
Knownhistory
historyof
of CAD,
CAD, including
including MI Recent cocaine
Recent cocaineuse
use
New
Newchest
chestor
orleft
leftarm
arm pain
pain or
or discomfort
as
aschief
chiefsymptom
symptom
Age
Agegreater
greaterthan
than70
70 years
years
Male
Malesex
sex
Diabetes
Diabetesmellitus
mellitus
Examination
Examination
Transient
TransientMR
MRmurmur,
murmur, hypotension,
hypotension, Chest discomfort
Chest discomfortreproduced
reproduced
diaphoresis,
diaphoresis,pulmonary
pulmonary edema,
edema, or rales by palpation
by palpation
Extracardiac
Extracardiacvascular
vascular disease
disease
ECG
ECG
New,
New,ororpresumably
presumably new,
new, transient
transient ST- T-wave flattening
T-wave flatteningororinversion
inversion
segment
segmentdeviation
deviation (1
(1 mm
mm or
or greater)
greater) or T- less
less than
than 11mm
mmininleads
leadswith
with
wave
waveinversion
inversionin
in multiple
multiple pre-cordial
pre-cordial dominant
dominant RRwaves
waves
leads
leads
Normal ECG
Normal ECG
Cardiac
CardiacBiomarkers
Biomarkers
Elevated
Elevatedcardiac
cardiacTnI,
TnI, TnT,
TnT, or
or CK-MB Normal
Normal
markers
markers
Modified
Modifiedfrom
fromBraunwald
BraunwaldE,
E, et
et al.
al. Unstable
Unstable Angina: Diagnosis
Diagnosisand
andManagement.
Management.1994;3-1-
1994;3-1-
AHCPR
AHCPRPublication
PublicationNo
No94-0602:1-154.
94-0602:1-154.
55
55
53
APPENDIX IV : TIMI RISK SCORE FOR UA/NSTEMI

APPENDIX IV : TIMI RISK SCORE FOR UA/NSTEMI
TIMI Risk Score All-Cause Mortality, New or Recurrent
TIMI Risk Score All-Cause Mortality, New or Recurrent
MI, or Severe Recurrent Ischemia
MI, or Severe Recurrent Ischemia
Requiring Urgent Revascularization
Requiring Urgent Revascularization
Through 14 d After Randomization, %
Through 14 d After Randomization, %
0-1 4.7
0-1 4.7
2 8.3
2 8.3
3 13.2
3 13.2
4 19.9
4 19.9
5 26.2
5 26.2
6-7 40.9
6-7 40.9
The TIMI risk score is determined by the sum of the presence of 7 variables at
The TIMI risk score is determined by the sum of the presence of 7 variables at
admission:
admission:
1 point is given for each of the following variables:
1 point is given for each of the following variables:
Age 65 y or older
Age3 65
At least risky factors
or olderfor CAD ( family history of premature CAD,
At least 3 risk factors
hypertension,elevated for CAD (active
cholesterols, familysmoker,
history of premature CAD,
diabetes)
Known hypertension,elevated
CAD (coronary stenosis cholesterols,
of > 50%)active smoker, diabetes)
Use ofKnown
aspirinCAD (coronary
in prior 7 daysstenosis of > 50%)
Use of aspirin in prior
ST-segment deviation (>0.5mm) 7 dayson ECG
ST-segment
At least deviation in
2 anginal episodes (>0.5mm)
prior 24 on
h ECG
At least
Elevated serum2 anginal
cardiacepisodes
biomarkersin prior 24 h
Elevated serum cardiac biomarkers
Total Score = 7 points
Total Score = 7 points
Low Risk : < 2 point
Low Risk
Moderate Risk: :3-4 2 point
< points
HighModerate
Risk : >5Risk:
points3-4 points
High Risk : >5 points
Adapted from :
Adapted
Antmanfrom
EM,: Cohen M, Bernink PJ, et al. The TIMI risk score for unstable
Antman EM,
angina/non-ST Cohen
elevation MI: M, Bernink
a method forPJ, et al. The and
prognostication TIMItherapeutic
risk scoredecision
for unstable
angina/non-ST
making. JAMA 2000; 284 elevation MI: a. method for prognostication and therapeutic decision
: 835–42
making.
Sabatine MS,JAMAMorrow2000; 284Giugliano
DA, : 835–42 . RP, et al. Implications of upstream
SabatineIIb/IIIa
glycoprotein MS, inhibition
Morrow DA, and Giugliano
coronary RP,arteryet stenting
al. Implications of upstream
in the invasive
glycoprotein
management IIb/IIIa inhibition
of unstable angina/nonandSTcoronary
elevationartery stentinginfarction.
myocardial in the invasive
A
management
comparison of unstable inangina/non
of the Thrombolysis Myocardial ST elevation
Infarction myocardial
(TIMI) infarction.
IIIB trial and the A
Treat angina with Aggrastat and determine Cost of Therapy with Invasive or the
comparison of the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial and
Treat angina with Aggrastat and determine Cost of Therapy
Conservative Strategy (TACTICS)-TIMI 18 trial. Circulation 2004; 109 : 874-880. with Invasive or
Conservative Strategy (TACTICS)-TIMI 18 trial. Circulation 2004; 109 : 874-880.
56
56
54
APPENDIX
APPENDIXV: V:
GRACE
GRACEPREDICTION SCORE
PREDICTION CARD
SCORE AND AND
CARD NOMOGRAM
NOMOGRAM
FOR ALLALL
FOR CAUSE MORTALITY
CAUSE FROM
MORTALITY DISCHARGE
FROM TO 6 TO 6
DISCHARGE
MONTHS*
MONTHS*
*Eagle KA,Lim MJ,Dabbous OH et al for the Grace Investigators. A Validated Prediction Model for All
Forms of Acute Coronary Syndrome.Estimating the Risk of 6-Month Postdischarge Death in an
International Registry JAMA. 2004;291:2727-2733.
*Eagle KA,Lim MJ,Dabbous OH et al for the Grace Investigators. A Validated Prediction Model for
Forms of Acute Coronary Syndrome.Estimating the Risk of 6-Month Postdischarge Death in an
57
International Registry JAMA. 2004;291:2727-2733.
57
55
APPENDIX
APPENDIX
VI: VI:
Calculation
Calculation
Of Creatinine
Of Creatinine
Clearance
Clearance
APPENDIX
APPENDIX
VI: Calculation
VI: Calculation
Of Creatinine
Of Creatinine
ClearanceClearance
Estimated
Estimated GFRGFR (ml/min)
(ml/min)
= (140-age)
= (140-age)x weight
x weight or or1.2 (140-age)
1.2 (140-age)
Estimated Estimated
GFR (ml/min) GFR= (ml/min)
(140-age)
= (140-age)
x weight x weight
or 1.2 (140-age)
or 1.2 (140-age)
(0.814
(0.814
x SCrx [µmol/L
SCr [µmol/L
]) ]) SCr [µmol/L
SCr [µmol/L
] ]
Cr [µmol/L
(0.814 x S(0.814 ]) [µmol/LS])Cr [µmol/LSCr
x SCr ] [µmol/L ]
SCr : S
serum
Cr : serum
creatinine
creatinine
SCr : serumScreatinine
Cr : serum creatinine
For women
For women multiply
multiply
by 0.85
by 0.85
For women For
multiply
women bymultiply
0.85 by 0.85
Severity
Severity
Of CKD*
Of CKD*
Severity OfSeverity
CKD* Of CKD*
SEVERITY
SEVERITY OF CKD
OF CKD CREATININE
CREATININE CLEARANCE
CLEARANCE
SEVERITYSEVERITYOF CKD OF CKD CREATININE CREATININE
CLEARANCE CLEARANCE
NormalNormal to mildto mild >60 >60
ml/min
ml/min
Normal toNormalmild to mild >60 ml/min>60 ml/min
Moderate
Moderate 30-59 30-59
ml/min
ml/min
Moderate Moderate 30-59 ml/min30-59 ml/min
SevereSevere <30 <30
ml/min
ml/min
Severe Severe <30 ml/min<30 ml/min
* National
* National
Kidney
Kidney
Foundation.
Foundation.
K/DOQI
K/DOQI
clinical
clinical
practice
practice
guidelines
guidelines
for chronic
for chronic
* kidney
kidney
National disease:
disease:
*Kidney
Nationalevaluation,
evaluation,
Foundation.
Kidney classification,
classification,
Foundation.
K/DOQI clinical
K/DOQIand and
stratification.
practice stratification.
clinical practiceAm
guidelines forAm
Jchronic
Kidney
J Kidney
guidelines for chronic
Dis.2002;
kidney Dis.2002;
39 (suppl
disease:
kidney39evaluation,
(suppl
1): S1–S226
disease: 1): S1–S226
evaluation,
classification,
classification,
and stratification.
and stratification.
Am J Kidney Am J Kidney
Dis.2002; 39Dis.2002;
(suppl 1):
39S1–S226
(suppl 1): S1–S226
APPENDIX
APPENDIX
VII: Prevention
VII: Prevention
of Contrast
of Contrast
Induced
Induced
Nephropathy
Nephropathy
APPENDIX
APPENDIX
VII: Prevention
VII: Prevention
of Contrast
of Induced
ContrastNephropathy
Induced Nephropathy
ACC/ESC
ACC/ESC
Classification
ACC/ESCClassification
ACC/ESC
ClassificationClassification
Contrast
Contrast
AgentAgent
- Isomolar
Contrast- Isomolar
agent
Agent
Contrastagent
Agent I, A I, A
- Low- Low
- Isomolar osmolar
osmolar
-agent agents
Isomolar agents
agent IIa,
I, A BIIa, B I, A
- use-osmolar
- Low use
minimal
minimal
- Low volume
volume
agents
osmolar agents IIa, I,B C I, C
IIa, B
- use minimal- usevolume
minimal volume I, C I, C
Avoid Avoid
nephrotoxic
nephrotoxic
agents
agents
eg eg I, C I, C
NSAIDS,metformin
NSAIDS,metformin
Avoid nephrotoxic
Avoid nephrotoxic
agents egagents eg I, C I, C
NSAIDS,metformin
NSAIDS,metformin
SalineSaline
Infusion
Infusion I, C I, C
Saline Infusion
Saline Infusion I, C I, C
SodiumSodiumBicarbonate
Bicarbonate IIa, BIIa, B
Sodium Bicarbonate
Sodium Bicarbonate IIa, B IIa, B
Acetylcysteine
Acetylcysteine IIb, BIIb, B
Acetylcysteine
Acetylcysteine IIb, B IIb, B
58 58
58 58
56
APPENDIX VIII:
APPENDIX VIII:Prevention ofofContrast
Prevention ContrastInduced
InducedNephropathy
Nephropathy
AGENT
AGENT CONCENTRATION DOSE
CONCENTRATION DOSE/ FLOW
/ FLOWRATE
RATE
Sodium
Sodium Chloride* 0.9%
Chloride* 0.9% solution
solution Rateofof1.0-1.5
Rate 1.0-1.5ml/kg/hr
ml/kg/hrfor
for
3h-12hbefore
3h-12h beforeandand6h-24h
6h-24h
afterthe
after theprocedure
procedureensuring
ensuring
a aurine
urineflow
flowrate
rateofof150
150
ml/hour
ml/hour
Reducerate
Reduce ratetoto0.5
0.5ml/kg/hr
ml/kg/hrifif
LVEF<40%
LVEF<40%
Sodium 154 mEq/L in 5% 3 ml/kg/hr for 1 hour before
Sodium 154 mEq/L in 5% 3 ml/kg/hr for 1 hour before
Bicarbonate** dextrose in water the contrast followed by an
Bicarbonate** dextrose in water the contrast followed by an
(154 ml of infusion of 1 ml/kg/hr for 6
(154 ml of
1000 mEq/l of
infusion of 1 ml/kg/hr for 6
hours after the procedure
1000 mEq/l
sodium of
bicarbonate hours after the procedure
sodium
+ 850 bicarbonate
ml of 5%
+ 850 ml of 5%
Dextrose)
Dextrose)
N- 1200 mg twice daily, one day
N-acetylcysteine*** 1200 mgand
before twice daily,
one day one
afterday
the
acetylcysteine*** before and one day after the
contrast
contrast
* McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of
* McCullough
isosmolar iodixanol compared
PA, Bertrand with low-osmolar
ME, Brinker JA, Stacul F.contrast media. J of
A meta-analysis Am theColl Cardiol.
renal safety 48:
of
2006; 692–9.
isosmolar iodixanol compared with low-osmolar contrast media. J Am Coll Cardiol. 48:
2006; 692–9.
** Briguori C, Colombo A, Violante A et al. Standard vs double dose of N-acetylcysteine to
prevent contrast
** Briguori agentA,associated
C, Colombo Violante Anephrotoxicity.
et al. StandardEurvsHeart J 2004;
double dose 25 : 206-211.
of N-acetylcysteine to
prevent contrast agent associated nephrotoxicity. Eur Heart J 2004; 25 : 206-211.
*** Tepel M, Van der Giet M, Schwarzfeld C et al. Prevention of radiographic-contrast-
*** agent-induced
Tepel M, Vanreductions in renal
der Giet M, functionCbyetacetylcysteine.
Schwarzfeld al. Prevention NofEngl J Med. 2000; 343:
radiographic-contrast-
180–184.
agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000; 343:
180–184.
59
59
57
ACKNOWLEDGMENTS
ACKNOWLEDGMENTS
The committee of this guideline would like to express their gratitude and
The committee
appreciation of this
to the guideline
following would
for their like to express their gratitude and
contribution:
appreciation to the following for their contribution:
Technical Advisory Committee, Clinical Practice Guidelines, Ministry of
Technical
Health for Advisory Committee,
their valuable input andClinical Practice Guidelines, Ministry of
feedback
Health
Panel offorexternal
their valuable input
reviewers whoand feedback
reviewed the draft
Panel of external
Secretarial reviewers
assistance from who reviewed the draft
sanofi-aventis
Secretarial assistance from sanofi-aventis
DISCLOSURE STATEMENT
DISCLOSURE STATEMENT
The panel members have no potential conflict of interest to disclose.
The panel members have no potential conflict of interest to disclose.
SOURCES OF FUNDING
SOURCES OF FUNDING
This CPG was made possible by an unrestricted educational grant from
This CPG was (M)
Sanofi-Aventis madeSdnpossible
Bhd. by
Theanfunding
unrestricted
body educational grant from
did not influence the
Sanofi-Aventis
content of this guideline. Bhd.
(M) Sdn The funding body did not influence the
content of this guideline.
60
60
58
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June 2011 MOH/P/PAK/219.

This guideline was developed to be a guide for best clinical practice

REVIEW OF THE GUIDELINE

Available on the following websites:

2. The diagnosis of UA/NSTEMI is based on history ± dynamic

3. In UA cardiac biomarkers are normal while in NSTEMI it is elevated.

4. Risk stratification is important for prognosis and to guide management

5. Initial management of intermediate/high risk patients includes optimal

6. Patients with refractory angina and/or hemodynamically unstable

7. Intermediate/high risk patients should be considered for early invasive

8. Low risk patients should be assessed non-invasively for ischemia I,A.

9. All patients should receive optimal medical therapy at discharge.

10. These drugs should be uptitrated as outpatient to the recommended

11. Cardiac rehabilitation and secondary prevention programs

Flowchart 1: Risk Stratification of UA/NSTEMI

Low risk Intermediate/High Risk

This includes (see Table 1, pg:4):

 Medical therapy* Coronary Angiography and Revascularization*

CCB : Calcium channel blockers

Table 1: Medications in Intermediate / High Risk Patients with UA/NSTEMI

Drug Initial and In- Medication Comments

Low Risk patients with UA/NSTEMI

Normal ECG, Abnormal ECG,

Negative test Positive Equivocal / Positive Test

Risk Factor Reduction +

* Low risk patients have :

no angina in the past

Patients who have undergone revascularization and with residual/recurrent or a

All Intermediate/High Risk UA/NSTEMI patients should be considered for coronary

MESSAGE FROM THE DIRECTOR GENERAL OF HEALTH

It is now recognized that early, aggressive management of UA/NSTEMI can

In this rapidly evolving landscape of UA/STEMI management, and a definite

Dato Hasan Abdul Rahman,

FOREWARD FROM THE AMERICAN COLEGE OF CARDIOLOGY

On behalf of the American College of Cardiology I want to offer my hearty

Congratulations and a personal toast to Malaysian heart health!

Ralph Brindis, MD, MPH, FACC, FSCAI

Immediate Past President,

Members of the Expert Panel

External Reviewers (in alphabetical order):

Dr. Chan Hiang

Dr. Lee Chuey

Dr. Lee Fatt

Dr. Kim Tan

Dr. Tee Lian

Dr. Wong Kai

RATIONALE AND PROCESS OF GUIDELINE DEVELOPMENT

Coronary artery disease (CAD) is an important cause of morbidity and

The objectives of this guideline are to:

This Clinical Practice Guideline (CPG) has been drawn up by a committee

Evidence was obtained by systematic review of current medical literature

The level of recommendation and the grading of evidence used in this

Clinical Questions Addressed:

What is the current evidence on the best practice strategies to

This guideline is directed at healthcare providers including general

All patients (older than 18 years) presenting with chest pain.

Period of Validity of the Guidelines:

This guideline needs to be revised at least every 5 years to keep abreast

Applicability of the Guidelines:

This guideline aims to streamline management of cardiac patients and

Implementation of the Guidelines:

The implementation of the recommendations of a CPG is part of good

increasing public awareness of CAD and its therapies.