MOH/P/PAK/219.11 (GU) June 2011

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
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), -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.
Flowchart 1: Risk Stratification of UA/NSTEMI
Flowchart 1: Risk Stratification of UA/NSTEMI
Intermediate/High Risk Patients with recurrent chest pain Early post infarction unstable angina Dynamic ST-segment changes Elevated cardiac biomarkers Diabetes Hemodynamic instability Depressed LV function (LVEF <40%) Major arrhythmias (VF, VT) Low risk no angina in the past no ongoing angina no prior use of antianginal therapy normal ECG normal cardiac biomarkers normal LV function 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) -blockers Statins ACE-I/ARB Nitrates + CCB (if -blockers contraindicated and/or unresponsive to above) + GP IIb/IIIa inhibitor Coronary Angiography and Revascularization*
*If patient is admitted to a non-PCI centre and has ongoing ischaemia despite optimal medical therapy, it is recommended to transfer the patient for coronary angiography with view to revascularization.
Medical therapy* * This includes aspirin +
blockers + GTN
Risk stratify as outpatient (Fig1, pg 5)
CCB : Calcium channel blockers UFH : Unfractionated heparin LMWH : Low Molecular Weight Heparin GP : Glycoprotein VF: Ventricular fibrillation VT: Ventricular tachycardia
Table 1: Medications in Intermediate / High Risk Patients with UA/NSTEMI
Table 1: Medications in Intermediate / High Risk Patients with UA/NSTEMI
Drug Aspirin + Clopidogrel Initial and Inhospital medication I,A I,A Medication at discharge I,A I,A I,B Comments Continued long term if tolerating Used in addition to aspirin as part of dual antiplatelet therapy. To be continued at least 1 month and ideally for at least a year post UA/NSTEMI and, 6-12months or longer post DES implantation Used in addition to aspirin as part of dual antiplatelet therapy. This is a less preferred alternative to clopidogrel. Used in addition to aspirin as part of dual antiplatelet therapy. Alternative to clopidogrel in high risk patients undergoing PCI. Used in addition to aspirin as part of dual antiplatelet therapy. Alternative to clopidogrel. Given for 2-8 days Given for 2-8 days Used in patients treated conservatively. Given for 8 days or duration of hospitalization Used as an alternative to UFH and GPIIb/IIIa inhibitors during PCI Should be administered early if no contraindications and continued indefinitely if ischemia is present. Continued indefinitely in the presence of LV dysfunction (LVEF<40%) Should be administered early in patients with LV dysfunction (LVEF< 40%), heart failure, diabetes, hypertension or CKD. Should be considered long term to prevent recurrent ischemia As an alternative to ACE-I in intolerant patients High potency statins should be used early till target LDL-C levels are achieved and continued indefinitely. If intolerant to -blockers Indicated for residual/ recurrent ischemia. Indicated for residual/ recurrent ischemia.
I,C or, Ticlopidine IIa,B IIa,B
or, prasugrel
I,B
I,B
or, ticagrelor
I,B
I,B
+ UFH or, LMWH or, fondaprinux or, Bivalirudin + -blockers
I,A I,A I,A
I,A 1,B I,B
I,A + ACE-I I,A I,A
IIa, A or ARB + Statins I,B I, A I,B I,A
+/- calcium channel blockers +/- nitrates
1,B IIa,C I,C
I,B IIa,C I,C
Figure 1: Non-invasive investigation of Low Risk Patients with UA/ NSTEMI*
Low Risk patients with UA/NSTEMI
Figure 1: Non-invasive investigation of Low Risk Patients with UA/NSTEMI*
Normal ECG, Good Exercise Tolerance
Abnormal ECG, Limited exercise tolerance Exercise/Dobutamine Stress Echocardiogram or Radionuclear Perfusion Scan
Exercise stress test
Equivocal
Negative test
Positive
Equivocal / Positive Test
Risk Factor Reduction + Medical Therapy for CAD
Coronary Angiogram
* 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)
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
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, NHAMs Class 1 recommendations for the management of ACS/NSTEMIs represent the must dos 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. NHAMs 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 dont measure it, we cant manage it!! We applaud the leadership of the National Heart Association of Malaysia with its enthusiasm and expertise manifested in NHAMs 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
Members of the Expert Panel Members of Members the Expert of Panel the Expert Panel
erson: Chairperson: Consultant Cardiologist, Consultant Cardiologist, Sime DarbySime Medical Darby Center Medical Center Subang Jaya, Subang Selangor Jaya, Selangor
amalar Dr.Rajadurai Jeyamalar Rajadurai
Members ers (in Members alphabetical (in alphabetical order) order) (in alphabetical order)
Consultant Cardiologist, Consultant Cardiologist, Sime DarbySime Medical Darby Center Medical Center Subang Jaya,Selangor Subang Jaya,Selangor Consultant Cardiologist, Consultant Cardiologist, Hospital Serdang Hospital Serdang Consultant Physician, Consultant Physician, Hospital Sultanah Hospital Bainun, Sultanah Ipoh Bainun, Ipoh Consultant Cardiologist, Consultant Cardiologist, Hospital Besar Hospital Pulau Besar Pinang Pulau Pinang Consultant Cardiologist Consultant Cardiologist Hospital UKM, Hospital KualaUKM, Lumpur Kuala Lumpur
mad Nizar Dr. Ahmad Nizar
uar Rapaee Dr. Anuar Rapaee Chandran Dr. Aris Chandran
ar Ismail Dr. Omar Ismail
h Maskon Dr. Oteh Maskon
e Raman Dr. Sree Raman
Consultant Physician, Consultant Physician, Hospital Tuanku Hospital Jaafar, Tuanku Seremban Jaafar, Seremb (HTA trained) (HTA trained)
Kui Dr. Hian Sim Kui Hian
Consultant Cardiologist, Consultant Cardiologist, Sarawak General Sarawak Hospital,Kuching General Hospital,Kuchi
n Azman Dr. Wan Azman
Consultant Cardiologist, Consultant Cardiologist, University Malaya University Medical Malaya Center Medical Cente Consultant Cardiologist, Consultant Cardiologist, Institute Jantung Institute Negara, Jantung Negara, Kuala Lumpur Kuala Lumpur
bayaah Dr.Zambahari Robayaah Zambahari
External Reviewers (in alphabetical order): External Reviewers External Reviewers (in alphabetical (in alphabetical order): order):
Dr. Chan Hiang Dr. Chan Chuan Hiang Chuan
Consultant Consultant Physician Physician Sarawak General Sarawak Hospital,Kuching General Hospital,Ku Consultant Consultant Physician Physician Head of Internal Head of Medicine, Internal Medicine, Ministry Of Ministry Health, Of Health, Hospital Kuala Hospital Lumpur Kuala Lumpur
Dr. Jeyaindran Dr. Jeyaindran Sinnadurai Sinnadurai
Dr. Lee Chuey Dr. Lee Yan Chuey Yan
Consultant Consultant Cardiologist Cardiologist Hospital Sultanah HospitalAminah Sultanah Johor Aminah Joh Consultant Consultant Geriatrician Geriatrician Hospital Kuala Hospital Lumpur, Kuala KL Lumpur, KL Consultant Consultant Cardiologist, Cardiologist, Sunway Medical Sunway Center, Medical Center, Sunway,Selangor Sunway,Selangor Family Medicine FamilySpecialist, Medicine Specialist, Klinik Kesihatan Klinik Kesihatan Jelapang, Jelapang, Ipoh, Perak Ipoh, Perak
Dr. Lee Fatt Dr. Soon Lee Fatt Soon
Dr. Kim Tan Dr. Kim Tan
Dr. V Paranthaman Dr. V Paranthaman
Dr. Santha Dr. Kumari Santha Kumari
Consultant Consultant 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 General Practitioner, General Practitioner, LW Medical LW Associates Medical Associates Kuala Lumpur Kuala Lumpur
Dr. Wong Kai Dr. Wong Fatt Kai Fatt
Dr. Zurkarnai Dr. Yusof Zurkarnai Yusof
Consultant Consultant Cardiologist Cardiologist Hospital Universiti Hospital Sains Universiti Malaysia Sains Malay Kota Baru,Kota Kelantan Baru, Kelantan
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.
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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 ECGs 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.
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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.
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GRADES OF RECOMMENDATIONS AND LEVELS OF EVIDENCE GRADES OF RECOMMENDATION I II II-a II-b III Conditions for which there is evidence and/or general agreement that a given procedure/therapy is beneficial, useful and/or effective. Conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a procedure/therapy. Weight of evidence/opinion is in favor of its usefulness/efficacy. Usefulness/efficacy is less well established by evidence/opinion Conditions for which there is evidence and/or general agreement that a procedure/therapy is not useful /effective and in some cases may be harmful.
LEVELS OF EVIDENCE A B C Data derived from multiple randomized clinical trials or meta analyses Data derived from a single randomized clinical trial or large non randomized studies Only consensus of opinions of experts, case studies or standard of care
Adapted from the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC)
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TABLE OF CONTENTS Statement of Intent Summary Flowchart 1, Table 1, Figure 1 Message from Director General of Health, MOH Foreward from President of American College of Cardiology Members of the Expert Panel External Reviewers Rationale and Process of Guideline Development 1. Introduction 2. Definition of terms 3. Pathogenesis 4. Diagnosis 4.1 History 4.2 Physical Examination 4.3 Electrocardiography 4.4 Cardiac Biomarkers 4.5 Other Diagnostic Modalities 5. Risk Stratification 5.1 Assessment of Risk 5.2 Rationale for Risk Assessment 5.3 Risk Scores for Prognosis of UA/NSTEMI 5.4 Risk Assessment for Bleeding 6. Triage 7. Management of UA/NSTEMI 7.1 Pre hospital Management 7.2 In Hospital Management 7.2.1 Initial Management 7.2.2 Antiplatelet Agents 7.2.3 Anticoagulant Therapy 7.2.4 Anti Ischemic Drug Therapy 8. Revascularization strategies 8.1 Routine early invasive management 8.2 Routine early conservative management 9. UA/NSTEMI in special groups 9.1 UA/NSTEMI in Elderly 9.2 UA/NSTEMI in Women 9.3 UA/NSTEMI in Chronic Kidney Disease 9.4 UA/NSTEMI in diabetes 10. Post Hospital Discharge 10.1 Medications post discharge 10.2 Investigations during Follow Up 11. Cardiac Rehabilitation 12. References 13. Appendix 14. Acknowledgement 15. Disclosure Statements 16. Source of Funding
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1 2 3-5 6 7 8 9 10-13 15 15-16 16 17-19 17 17 18 18-19 19 20-21 20 20 20 21 21-22 22-31 23 23-31 23 23-25 25-27 28-30 31-32 31 32 32-36 32-34 34 35 36 36-40 36-39 39-40 40-41 42-50 51-57 58 58 58
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 inpatient 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. II. III. New onset of severe angina or accelerated angina; no rest pain Angina at rest within past month but not within preceding 48 hours (angina at rest, subacute) Angina at rest within 48 hours (angina at rest, acute)
It may be further classified according to clinical circumstances into either: A) B) C) Secondary develops in the presence of extracardiac disease Primary develops in the absence of extracardiac disease Post-infarct develops within 2 weeks of an acute MI
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The diagnosis of NSTEMI is established if a cardiac biomarker is detected. The diagnosis of NSTEMI is established if a cardiac biomarker is detected. The diagnosis of NSTEMI is established if a cardiac biomarker is detected. In NSTEMI, ST/TST/T changes maymay be present in the ECG, whereas in UA In NSTEMI, changes be present in the ECG, whereas in UA In NSTEMI, ST/T changes may be present in the ECG, whereas in UA they they are usually absent and and even if they are present, are are usually transient. are usually absent even if they are present, usually transient. they are usually absent and even if they are present, are usually transient. FIGURE 2: Pathogenesis of ACS FIGURE 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 from Antman EM, Anbe DT, Armstrong PW et al.et ACC/AHA Guidelines Adapted with modification from Antman EM, Anbe DT, Armstrong PW al. ACC/AHA Guidelines for the management of patients with ST Elevation My ocardial Infarction at www.acc.org for thefor management of patients with ST Elevation My ocardial Infarction at www.acc.org the management of patients with ST Elevation My ocardial Infarction at www.acc.org
3. PATHOGENESIS 3. PATHOGENESIS 3. PATHOGENESIS ACS occurs due to atherosclerotic plaque rupture, fissure or ulceration occurs to atherosclerotic plaque rupture, fissure or ulceration ACS ACS occurs due due to atherosclerotic plaque rupture, fissure or ulceration with superimposed thrombosis and coronary vasospasm. Depending on superimposed thrombosis coronary vasospasm. Depending with with superimposed thrombosis and and coronary vasospasm. Depending on on the acuteness, degree of occlusion and the presence of collaterals, the acuteness, degree of occlusion presence of collaterals, the acuteness, degree of occlusion and and the the presence of collaterals, patients can present as UA, NSTEMI or STEMI. patients can present as UA, NSTEMI or STEMI. patients can present as UA, NSTEMI or STEMI. The aetiology of the plaque fissure or rupture is still unclear. Possible aetiology of plaque the plaque fissure or rupture is still unclear. Possible The The aetiology of the fissure or rupture is still unclear. Possible causes include inflammation, infection, uncontrolled blood pressure and causes include inflammation, infection, uncontrolled blood pressure causes include inflammation, infection, uncontrolled blood pressure andand smoking. ACS occurring de novo is called Primary UA/NSTEMI. smoking . ACS occurring de novo is called Primary UA/NSTEMI. smoking . ACS occurring de novo is called Primary UA/NSTEMI. Occasionally UA/NSTEMI is secondary to a precipitating condition, which Occasionally UA/NSTEMI is secondary a precipitating condition, which Occasionally UA/NSTEMI is secondary to ato precipitating condition, which is extrinsic to the coronary arterial bed. This is called secondary is extrinsic to the coronary arterial is called secondary is extrinsic to the coronary arterial bed.bed. ThisThis is called secondary UA/NSTEMI and can occur due to: UA/NSTEMI and occur can occur UA/NSTEMI and can due due to: to: increased myocardial oxygen demand as occurring in fever, increased myocardial oxygen demand occurring fever, increased myocardial oxygen demand as as occurring in in fever, tachycardia and thyrotoxicosis tachycardia and thyrotoxicosis tachycardia and thyrotoxicosis reduced coronary blood flow due to hypotension reduced coronary blood flow due to hypotension reduced coronary blood flow due to hypotension reduced myocardial oxygen delivery in anaemia or hypoxemia reduced myocardial oxygen delivery in anaemia or hypoxemia reduced myocardial oxygen delivery in anaemia or hypoxemia Secondary UA/NSTEMI is an important cause of ACS in the elderly. Secondary UA/NSTEMI is an important cause of ACS in the elderly. Secondary UA/NSTEMI is an important cause of ACS in the elderly.
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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.
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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 patients 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.
I, C
However, a completely normal ECG does not exclude the diagnosis 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

I, A
Cardiac troponins (troponin T or I) are the recommended 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 612 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 514 days after the acute event.
17 Non coronary are extremely rare It. It may o Non coronary causes causes for forelevated elevatedtroponins troponins are extremely rare . 17 may occur in acute myocarditis, pulmonary embolism, acute myocarditis, acute pulmonaryacute embolism, a dissecting aorticaaneurysm dissecting aortic heart failureSevere and sometimes in heart failure and aneurysm, sometimesacute in septic shock. 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 in thein absence of ACS. in Athese raised level (Appendix is however with an increase all cause mortality patients. II, pg 52) associated with an increase in all cause mortality in these patients. (Appendix II, pg 52) 18
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Creatinine kinase (CK) and its MB fraction (CKMB) are also important Creatinineof kinase (CK) and its MB fraction (CKMB) are also important indicators myocardial necrosis (infarction). They are however, less indicators of specific myocardial necrosis (infarction). They however, less sensitive and compared to cardiac troponins. CK are and CKMB have sensitive compared to cardiac troponins. and CKMB have a shorter and halfspecific life and hence are more useful thanCK troponins when a shorter reinfarction. half life and hence are more useful than troponins when diagnosing diagnosing reinfarction. All patients with NSTEMI have raised troponins, however, the CKMB may 18,19 be normal in 10-20% of have theseraised patients . Ahowever, raised CKMB in the All patients with NSTEMI troponins, the CKMB may 18,19 18,19 presence of a normal troponin level has no prognostic . A significance raised CKMB . in the be normal in 10-20% of these patients 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 of chest pain. A negative test within 4-8 hours of chest pain Myoglobin is not cardiac specific. It can be detected as early as 2 hours is useful in ruling out pain. myocardial necrosis (infarction). It should not after the onset of chest A negative test within 4-8 hours of chest pain however bein used as the only biomarker necrosis to identify (infarction). patients with It NSTEMI. is useful ruling out myocardial 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;90:99106)
(Adopted from Clinical Implications of the new definition of myocardial infarction. John K French, 4.5 Other diagnostic modalities 4.5 Other diagnostic modalities Harvey D White; Heart 2004;90:99106)
IIa, B
IIa, B
Echocardiogram LV systolic function is an important 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 is based on history + dynamic ECG 19 (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 A raised troponin level has diagnostic 19 and prognostic significance I,A. 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 stratication 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 rene risk stratication, thereby improving patient care in routine clinical rene risk stratication, thereby improving patient care in routine clinical practice 23 . We have proposed a simplified risk stratification model as practice 23. 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 Risk Score ACUITY HORIZONS-AMI24 Bleeding 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. 6. TRIAGE 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 patients clinical status: evaluation of patients 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. II. Intermediate/high risk 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 7.1 Pre-hospital Management Based on the triage: 7.1 Pre-hospital Management Based on the triage: If the history Based on the triage: is suggestive of ACS : - history Give soluble aspirin 300 crushed stat If the is suggestive of mg ACS : - history Give sublingual GTN If the is suggestive of mg ACS : soluble aspirin 300 crushed stat 12 lead ECG and cardiac biomarkers soluble aspirin 300 mg crushed stat - Do Give sublingual GTN Give sublingual - Do 12 lead ECGGTN and cardiac biomarkers - Do 12 lead ECG and cardiac biomarkers If the ECG and cardiac biomarkers are suggestive of ACS - ECG Give and clopidogrel 300 mg stat if are available. If the cardiac biomarkers suggestive of ACS -- ECG Send the cardiac patient300 to the healthcare facility where If the and biomarkers suggestive of ACS Give clopidogrel mgnearest stat if are available. definitive be given. mgnearest stat if available. -- Give Sendclopidogrel the treatment patient300 to can the healthcare facility where - Send the treatment patient to can the nearest healthcare facility where definitive be given. definitive treatment can be given. If the ECG and cardiac biomarkers are inconclusive for ACS Low risk patients : they canare be inconclusive referred as outpatient If the- ECG and cardiac biomarkers for ACS for cardiac assessment. (Fig 1, pginconclusive 5) If the- ECG and cardiac biomarkers are for ACS Low risk patients : they can be referred as outpatient Intermediate / High patients : should be admitted - Low risk patients : Risk they can referred as outpatient for cardiac assessment. (Fig 1, be pg 5) . cardiac assessment. (Fig 1, pg 5) - for Intermediate / High Risk patients : should be admitted - - 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 Initial management General Measures 7.2 Management (Table1, pg 4) 7.2.1 Initial management General Measures Following risk stratification: 7.2.1 Initial management General Measures Following risk stratification: low risk patients may be treated as outpatient. Following risk stratification: low risk patients may be treated as outpatient. High risk patients preferably should be admitted to CCU/HDU low risk patients may be treated as outpatient. I, C High risk patients preferably should be admitted to CCU/HDU with continuous ECG monitoring. I, C High risk patients preferably should be admitted to CCU/HDU with continuous ECG monitoring. I, C supplemental oxygen should be given to maintain SpO2 >90%, with continuous ECG monitoring. supplemental oxygen should be failure, given torespiratory maintain SpO in patients with left ventricular distress or 2 >90%, I, B supplemental oxygen should be failure, given torespiratory maintain SpO 2 >90%, in patients left ventricular distress or having high with risk features for hypoxemia. I, B in patients left ventricular failure, respiratory distress or I, B having high with risk features for hypoxemia. for pain relief, (intravenous 2 mg to 5 mg) together having high riskmorphine features for hypoxemia. IIa,B for pain relief, morphine (intravenous 2 mg 5given. mg) together with concomitant intravenous anti-emetic mayto be IIa,B for pain relief, morphine (intravenous 2 mg to 5given. mg) together with concomitant intravenous anti-emetic may be IIa,B 7.2.2. Medications - Antiplatelet agents with concomitant intravenous anti-emetic may be given. 7.2.2. Medications - Antiplatelet agents 7.2.2.1 Oral antiplatelet agents 7.2.2. Medications - Antiplatelet agents 7.2.2.1 Oral antiplatelet agents 7.2.2.1.1 Acetylsalicylic acid (ASA) 7.2.2.1 Oral antiplatelet agents 7.2.2.1.1 Acetylsalicylic acid (ASA) Recommended loading dose: 300 mg of soluble/chewable Acetylsalicylic acid (ASA) I, A 7.2.2.1.1 26,27 . Enteric coated aspirin not for aspirin Recommended loading dose: 300 is mg of recommended soluble/chewable I, A 26,27 initial loading dose because ofaspirin its slow onset of action. Recommended loading dose: 300 mg of recommended soluble/chewable . Enteric coated is not for aspirin I, A 26,27 . Enteric coatedofaspirin isonset not recommended for aspirin initial loading dose because its slow of action. 24 initial loading dose because of its 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 Antagonists These include: Diphosphate (ADP) Receptor
I, A
Clopidogrel loading dose: 300 to 600 mg, maintenance dose: 75 mg/day 28,29 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. 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.
IIa, B
I, B
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
Clinical Practice Guidelines on
management of Unstable Angina/Non 32 ST small increase in non CABG related major bleeding . Elevation Myocardial Infarction (UA/NSTEMI) 2011 with symptoms or need for a pacemaker. There was also a
with symptoms or need for a pacemaker. There was also a
7.2.2.2 Intravenous Antiplatelet Therapy Glycoprotein small increase in non CABG related major bleeding 32. (GP) IIb/IIIa Inhibitors 7.2.2.2 Intravenous Antiplatelet Therapy Glycoprotein (GP) include: IIb/IIIa These Inhibitors Abciximab These include: Tirofiban Abciximab Eptifibatide Tirofiban Eptifibatide These agents may be used in high risk patients awaiting transfer to a PCI facility for an early invasive strategy. Its routine use as 33,34 These agents may be used in high risk patients upstream therapy prior to PCI is now no longer awaiting practicedtransfer . to a PCI facility for an early invasive strategy. Its routine use as 33,34 upstream therapy prior to PCI is now no longer practiced . 7.2.3. Anticoagulant Therapy 7.2.3. Anticoagulant Therapy These include: (Table 2, pg 27)
I, A I, A I, A I, A I, A I, A
These include: (Table 2, pg 27) Unfractionated heparin (UFH) Unfractionated heparin (UFH) Low Molecular Weight Heparin (LMWH)-Enoxaparin 35,36,37 Anti Xa inhibitor-Fondaparinux Low Molecular Weight Heparin (LMWH)-Enoxaparin 35,36,37 Anti - Xa Itinhibitor-Fondaparinux is best used in UA/NSTEMI patients treated conservatively 38,39. - It is is associated best used in an UA/NSTEMI treated with increase in patients catheter-related 38,39 . conservatively thrombus and coronary angiographic complications. - It is with an increase in catheter-related is associated not recommended as the sole anticoagulant 38,39 coronary angiographic complications. thrombus during PCIand . is not as the the patient sole anticoagulant - It If used in recommended UA/NSTEMI and requires an 38,39 during PCI . UFH should be given during the invasive strategy, - If used in UA/NSTEMI the itpatient requireswith an procedure. When used and in PCI, is associated 38,39,40 invasive strategy, UFH given lower bleeding rates thanshould LMWHbe . during the procedure. When used in PCI, it is associated with 38,39,40 lower bleeding . undergoing Presently newer oralrates antithan Xa LMWH inhibitors are evaluation for ACS. Presently newer oral anti Xa inhibitors are undergoing evaluation for ACS. Anti IIa inhibitors Bivalirudin Anti Bivalirudin - IIaItinhibitors may be used as a substitute for heparin in patients with heparin-induced thrombocytopenia (HIT) 41. may be used as a substitute foras heparin in patients - It is reasonable to use bivalirudin an alternative to 41 . with thrombocytopenia (HIT) UFHheparin-induced and GP IIb/IIIa inhibitors in patients undergoing 42-45 - PCI It is reasonable to use bivalirudin as an alternative to . and GP IIb/IIIa inhibitors in patients undergoing - UFH It is associated with less 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
I, B I, B I, A I, A
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 UFH UA/NSTEMI DOSING REGIMEN 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 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 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 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 0.1 mg/kg bolus and 0.25 mg/kg/hour infusion 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 2.5 mg sc daily for 8 days or duration of hospitalization 38,39 If used during PCI, additional 50-60 IU/ kg UFH is recommended.
During PCI
Enoxaparin UA/NSTEMI
During PCI
Bivalirudin UA/NSTEMI During PCI
Fondaparinux UA/NSTEMI During PCI
* 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
I, C
Nitrates (Table 3, pg 29)
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. 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 (depending upon the half-life of the agent)
I, C
ingestion
7.2.4.2
I, B
-blockers (Table 4, pg 29)
In the absence of contraindications, -blockers should be administered early. Contraindications for -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 Sublingual Route Intravenous Sublingual Dosage 0.3 - 0.6 mg, can repeat up to 3 times at 5 minute Dosage intervals 0.3 - 0.6 mg, can repeat up 53 times 200 g/min* to at 5 minute intervals 0.4 0.8 mg per metered dose, no more than 3 5 200 g/min* sprays at 5 minute intervals 0.4 0.8 mg per metered dose, no more than 3 2.5 20 mg over 12 hours sprays at 5 minute on, then 12 hours off intervals 2 12 mg / hour 2.5 20 mg over 12 hours Time of Onset 2 minute Time of Onset 12 minute minute
Table 3: Recommended dosages of Nitrates in UA/NSTEMI*

Compound
Nitroglycerine, Glyceryl trinitrate Nitroglycerine, Glyceryl trinitrate
Intravenous GTN Spray
minute 21 minute
GTN Spray Transdermal patch

Intravenous Transdermal patch Oral Intravenous Oral (LA) Oral
2 minute 1 2 hours
1 minute 1 2 hours 30 60 minutes 1 minute
Isosorbide dinitrate
Isosorbide Isosorbide dinitrate mononitrate
then hours off 10 on, 20 mg,12 2 3 times daily 2 12 mg / hour

mg 2 daily, 10 30-60 20 mg, 3 times ( max 120 mg ) daily
30 60 minutes
*The dose of IV nitrates should be titrated every 5 10 minutes until symptoms and/or Isosorbide 30-60 mg daily, ischaemia is relieved and the desired haemodynamic response is obtained Oral (LA) 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 the desired haemodynamic response is obtained Table 4: Recommended dosages of -blockers in UA/NSTEMI*
Type Initiation dose Target dose Table 4: Recommended dosages of -blockers in UA/NSTEMI* Metoprolol 25 mg bd 100 mg bd
Type Atenolol Metoprolol Bisoprolol Atenolol Carvedilol Bisoprolol *As stated in MIMS Malaysia Carvedilol
Initiation dose 25 mg od 25 mg mg od bd 1.25 25 mg 3.125 mg od bd 1.25 mg od 3.125 mg bd
Target 100 mg dose od 100 mg 10 mg odbd 100 mg 25 mg bdod 10 mg od 25 mg bd
30
30
29
7.2.4.3 7.2.4.3 Calcium Calcium Channel Channel Blockers Blockers (Table 5, pg 5, 30) pg 30) 7.2.4.3 Calcium Channel Blockers (Table 5, (Table pg 30) Calcium Calcium channel channel blockers blockers (CCB) (CCB) may may be in be used used in UA/NSTEMI in UA/NSTEMI in the Calcium channel blockers (CCB) may be used UA/NSTEMI in the in the following following situations: situations: following situations: Verapamil Verapamil or diltiazem or diltiazem as an as an alternative alternative to patients to patients who areare not not Verapamil or diltiazem as an alternative to patients who arewho not 48 48 able able to tolerate to tolerate or who or who have have contraindication contraindication to to blockers. 48 blockers. able to tolerate or who have contraindication to blockers. Continuing Continuing or recurring or or recurring recurring angina angina despite angina despite adequate despite adequate adequate doses of doses doses of of IIa,C IIa,CIIa,C Continuing nitrates nitrates nitrates andand -blockers and -blockers -blockers verapamil, verapamil, verapamil, diltiazem, diltiazem, diltiazem, slow release slow slow release release nifedipine nifedipine nifedipine andand amlodipine. and amlodipine. amlodipine. Prinzmetals Prinzmetals Prinzmetals angina angina (variant angina (variant angina) (variant angina) angina)
I, B I, B I, B
Short-acting Short-acting Short-acting dihydropyridine dihydropyridine dihydropyridine CCB CCB should CCB should beshould avoided be avoided be avoided III, III, A III, AA
Table Table Table 5: 5: Recommended Recommended 5: Recommended dosages dosages dosages of Calcium of Calcium of Channel Calcium Channel Blockers Channel Blockers in Blockers UA/NSTEMI* in UA/NSTEMI* in UA/NSTEM Drug Drug Drug Diltiazem Diltiazem Diltiazem Dose Dose Dose Immediate Immediate release release 30-90 30-90 mg mg tds tds Immediate release 30-90 mg tds Slow Slow release Slow release 100-200 release 100-200 mg 100-200 od mg mg od od Verapamil Verapamil Verapamil Immediate Immediate release release 40-80 40-80 mg mg tds tds Immediate release 40-80 mg tds Slow release release 120-240 120-240 od od Slow Slow release 120-240 mg od mg mg Amlodipine Amlodipine Amlodipine Nifedipine Nifedipine Nifedipine 2.5-10 2.5-10 mg mg od od 2.5-10 mg od Slow Slow release Slow release 30-90 release 30-90 mg 30-90 od mg mg od od
*As *As stated stated in MIMS in MIMS Malaysia Malaysia *As stated in MIMS Malaysia
7.2.5 7.2.5 Lipid Lipid Modifying Modifying Drugs Drugs 7.2.5 Lipid Modifying Drugs
I, A A I, A soon soon after admission for for UA/NSTEMI cancan reduce major adverse soon after admission UA/NSTEMI reduce major adverse after admission for UA/NSTEMI can reduce major adverse
Current Current data data indicate indicate that early early initiation initiation high of high dose dose statin statin therapy therapy Current data indicate that that early initiation of highof dose statin therapy
49-54 49-54 49-54 cardiac events to its effects cardiac events due due to its pleotropic effects cardiac events due to pleotropic its pleotropic effects . Patients . Patients .with Patients ACS with with ACS ACS undergoing undergoing undergoing PCI, PCI, have PCI, have also have also been also been found been found to found benefit to to benefit with benefit the with with the the administration administration administration of high of high of dose high dose statins dose statins before statins before and before within and and 10 within days within 10 of days 10 the days of the of the 55-57 55-57 . 55-57 . . procedure procedure procedure
The The statins The statins statins thatthat have that have been have been studied been studied in studied UA/NSTEMI in UA/NSTEMI in UA/NSTEMI to date to are: date to date are: are: Atorvastatin Atorvastatin Atorvastatin 80 mg 80 od mg 80 mg od od Simvastatin Simvastatin Simvastatin 40 mg 40 od mg 40 mg od od
31
30
31 31
7.2.6 Angiotensin Converting Enzyme Inhibitor (ACE-I)/ARB (Table 7.2.6 Angiotensin Converting Enzyme Inhibitor (ACE-I)/ARB (Table 7,7, pg 39) pg 39)
I, A I, A
These should be considered early for patients with LV dysfunction These should be considered early for patients with LV dysfunction 55 . . and diabetes and diabetes 55 Key messages Key messages Patients Patientsshould shouldbe betreated treatedwith withoptimal optimalmedical medicaltherapy. therapy. (Table 1,1, pg 4) (Table pg 4)
I,C I,B I,C Nitrates , ,-blockers Nitrates I,C -blockers I,B+ +CCBs CCBs I,Care aregiven givenfor forrelief reliefofof ischemia. ischemia.
Statins I,AI,A ACE-I (for LV dysfunction, LVEF < 40%) I,AI,A Statins and and ACE-I (for LV dysfunction, LVEF < 40%) are 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 . (Flowchart 1, intermediate/high risk patients with UA/NSTEMI 56,57 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 procedure experience, technological improvements inWith PCI increasing and the development of new antiplatelet and anticoagulant in PCI and the development of new antiplatelet and anticoagulant regimens there is a general trend for early revascularization in regimens there is a general trend for early revascularization in these patients following optimal medical therapy. these patients following optimal medical therapy. 8.1. Routine early invasive management 58-61 8.1. Routine early invasive management 58-61 Urgent (as soon as possible after hospital presentation) 62 I, B 62 Urgent (as soon as possible after hospital coronary angiography/revascularization for presentation) patients with I, B coronary orangiography/revascularization with refractory recurrent angina associated for with patients dynamic ST refractoryheart or recurrent angina associated with dynamic ST deviation, failure, life threatening arrhythmias and/ or deviation, heart failure, life threatening arrhythmias and/ or hemodynamic instability hemodynamic instability Early (<72 hours) coronary angiography/revascularization- in I, A patients with hours) high-risk features as predicted by a positivein Early (<72 coronary angiography/revascularizationI, A biomarker assay, ST segment changes or a high score patients with high-risk features as predicted by risk a positive 58-61 according to assay, the TIMI scale or equivalent . a high risk score biomarker ST segment changes or according to the TIMI scale or equivalent 58-61. Routine invasive evaluation is not recommended in low risk IIb, B 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 for inducible silent ischemia. to have non-invasive However these patients or are recommended assessment for inducible or silent32 ischemia.
32
31
8.2 8.2Routine Routine early early 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 agents agents has has alsoalso reduced reduced the incidence the incidence of adverse of adverse outcomes outcomes in patients in patients 63,64,65 63,64,65 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 in or whom in whom objective objective evidence evidence of of significant significant ischemia ischemia is provoked is provoked in thein sub the acute sub acute phase. phase. A conservative A conservative strategy strategy is recommended is recommended for women for women who are who are 66 stabilized stabilized and and remain remain biomarker biomarker negative negative . 66. An early An early invasive invasive or conservative or conservative therapy therapy is a reasonable is a reasonable option option 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/NSTEMI treated treated conservatively conservatively are atare riskat ofrisk of developing developing recurrent recurrent adverse adverse cardiac cardiac events. events. Thus Thus these these patients patients need need to be to evaluated be evaluated periodically periodically for reversible for reversible ischemia ischemia using using non non invasive invasive tests.tests. If ischemia If ischemia is present, is present, they they should should be be considered considered for for coronary coronary angiography angiography and and revascularization. revascularization.
IIa, A IIa, A
IIa, A IIa, A
Key Key messages messages Patients Patients with with refractory refractory angina angina and/ and/ or hemodynamically or hemodynamically unstable unstable should considered for urgent coronary angiography should be be considered for urgent coronary angiography and and I,C revascularization revascularization . I,C. Intermediate/high Intermediate/high risk risk patients patients should 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 considered for transfer for transfer to a PCI to 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, pg 1,5) pg 5)
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 . . year year increase increase in age in 18,67-68 age18,67-68
33
32
33
9.1.1 9.1.1 Clinical Clinicalpresentation: presentation:
AA high high index index of of suspicion suspicion is is necessary necessary to make a diagnosis diagnosis of of UA/NSTEMI UA/NSTEMI in in elderly elderly patients. patients. Atypical Atypical presentations presentations occur more more frequently. frequently.These Theseinclude: include: dyspnoea dyspnoea diaphoresis diaphoresis nauseaand andvomiting vomiting nausea neurological neurological symptoms symptoms such such as as acute acute confusional states states and and syncope syncope ACS ACSfrequently frequentlydevelops develops as as a a secondary secondary coronary coronary event in the setting setting of ofanother anotheracute acute illness illness e.g. e.g. pneumonia. pneumonia. The The elderly often are in heart heart 69 .. The diagnostic. failure failureat atthe thetime timeof ofpresentation presentation 69 The ECGs ECGs may be non diagnostic.
9.1.2. 9.1.2. Management Management There especially Thereis islimited limitedtrial trial data data to to guide guide management management in the elderly especially in significant cocointhe thesetting setting of of advanced advanced age age (more (more than than 75 years) or significant morbidity consider the the morbidity(e.g. (e.g.prior prior stroke, stroke, renal renal impairment). impairment). One should consider biological when biological age age rather rather than than the the chronological chronological age of the patient when making group makingmanagement management decisions. decisions. The The elderly elderly are a heterogenous group and individualized. andthe therisk risk benefit benefit ratio ratio of of each each intervention intervention should be individualized. Creatinine drug Creatinine clearance clearance should should be be calculated calculated to enable appropriate drug dosing. dosing.(Appendix (AppendixVI,pg VI,pg56) 56)
I, I, AA
Bothaspirin aspirinand and clopidogrel clopidogrel (especially (especially in those undergoing Both undergoing PCI) PCI) 70,71 confergreater greaterabsolute absolute and and relative relative benefits benefits in the elderly 70,71 .. confer Prasugrel should should be be avoided avoided in in patients patients older than 75 years Prasugrel years in in 31 view viewof ofthe thebleeding bleedingrisk risk 31 .. In effective in in Inaameta-analysis, meta-analysis,both both UFH UFH and and LMWH LMWH were equally effective 72 . .However However bleeding bleeding risk risk is is higher with both agents. agents. the theelderly elderly72 Elderly use of of Elderlypatients patientshave have more more bleeding bleeding complications complications with the use 73,74 GPIIb/IIIa .. If If required, required, the the dose should be adjusted adjusted GPIIb/IIIainhibitors inhibitors 73,74 according accordingto tothe therenal renalfunction. function. The benefits with with The elderly elderly have have greater greater in-hospital in-hospital and long term benefits 75-79 .. In In some some trials, all the benefits of of an an an anearly earlyinvasive invasivestrategy strategy 75-79 early invasive strategy were in the elderly rather than in younger risk of major bleeding 80. patients 75. However there is an increased 34 34 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
I, I, BB
I, I, AA I, I, BB
I, I, AA
Clinical Practice Guidelines on management of Unstable Angina/Non ST Elevation Myocardial Infarction (UA/NSTEMI) 2011 early early early invasive invasive invasive strategy strategy strategywere were were in in inthe the theelderly elderly elderly rather rather ratherthan than thanin in in younger younger
75 75 75 80 .. However . However However there there there is is is an an an increased increased increased risk risk risk of of of major major major bleeding bleeding bleeding80 .. patients patients patients
When When Whenselecting selecting selectingpatients patients patientsfor for foran an anearly early earlyinvasive invasive invasivestrategy, strategy, strategy, the the risk risk benefit benefit benefit ratio ratio ratiomust must mustbe be beconsidered. considered. considered.For For Forpatients patients patientswith with withmulti multi multivessel vessel disease disease disease and and and not not not suitable suitable suitable for for for CABG, CABG, CABG, partial partial partial revascularization revascularization revascularizationof ofthe the culprit culprit culprit lesion lesion lesion may may may be be be a aa consideration. consideration. consideration. Long Long Long term term term management management management post post post discharge discharge discharge should should should include include medications medications medications that that that have have have been been been proven proven proven beneficial beneficial beneficial in in in secondary secondary secondary prevention. prevention. prevention. 9.2 9.2 UA/NSTEMI in Women UA/NSTEMI UA/NSTEMI in in Women Women
Women develop CAD about a decade Women develop develop CAD CAD about about aa decade decadelater later laterthan than thanmen men menat at ata a atime time timewhen when they are older and have more co-morbidity they are older older and and have have more more co-morbidity co-morbiditysuch such suchas as asobesity, obesity, obesity,diabetes, diabetes, diabetes, 81 81 .. . However However However gender gender gender is is is not not not an an hypertension hypertension hypertension and and and osteoarthritis osteoarthritis osteoarthritis 81 independent independent independent predictor predictor predictor of of of 1 11 year year year survival. survival. survival. 9.2.1 9.2.1 Clinical Clinical Clinical Presentation Presentation Presentation Women Women Women presenting presenting presenting with with with ACS ACS ACSoften often oftenhave have haveatypical atypical atypicalsymptoms symptoms symptomssuch such as as neck neck neckand and andshoulder shoulder shoulderache ache acheand and anddyspnoea. dyspnoea. dyspnoea.Often, Often, Often,women women women have have non non specific specific specific ECG ECG ECG changes changes changessuch such suchas as asT T Twave wave wavechanges changes changeseven even evenin in the the absence absence absenceof of ofheart heart heartdisease, disease, disease,thus thus thusmaking making making the the the diagnosis diagnosis diagnosis of of of CAD CAD difficult. difficult. difficult. 9.2.2 9.2.2 9.2.2 Management Management Management
InIn general, general, general, there there there are are are no no no gender gender gender specific specific specificdifferences differences differencesin in inthe the theefficacy efficacy efficacy ofofthe the thecommonly commonly commonlyused used useddrugs drugs drugsin in inACS. ACS. ACS.The The Thefollowing following following are are are some some important important important differences: differences: differences:
I, B I, B
Prasugrel is associatedwith withmore morebleeding bleedingin inindividuals individualswho Prasugrel Prasugrel is is associated associated with more bleeding in individuals who 31 31 31 are less than 60kg in weight .. . are are less less than than 60kg 60kg in in weight weight meta-analysis indicates indicates a a lack lack of of benefit benefit of of GPIIb/IIIa GPIIb/IIIa A A meta-analysis meta-analysis indicates a lack of benefit of GPIIb/IIIa 82 82 82 inhibitors in women .. The .The The bleeding bleeding bleeding risk risk risk is is is also also also higher. higher. higher. inhibitors inhibitors in in women women Thereis conflictingdata data regarding regarding the the benefits benefits of of an an early There There isisconflicting conflicting data regarding the benefits of an early 66,84-86 66,84-86 invasive strategyin inwomen womenwith withUA/NSTEMI UA/NSTEMI66,84-86 invasive invasive strategy strategy in women with UA/NSTEMI . ..Until Until Untilthis this issue issue issueis isisresolved resolved resolvedin in inrandomized randomized randomizedcontrolled controlled controlledtrials, trials, trials, an an an invasive invasive invasive strategy strategy strategy is isis best best best reserved reserved reserved for for for women women womenwith with withongoing ongoing ongoingischemia ischemia ischemiaand and raised raised raised troponins. troponins. troponins. UA/NSTEMI in Chronic Kidney Disease (CKD) In patients with ACS, the presence of CKD is an additional high35 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 Cockroft34 pg 56). Drug doses should be Gault formula (Appendix VI, adjusted according to renal function.
I, B I, B
IIa, IIa, AA
9.3
I, B
9.3
Clinical Guidelines UA/NSTEMI in Practice Chronic Kidney Disease (CKD) on
management of Unstable Angina/Non ST In patients with ACS, the presence of CKD is an additional highElevation Myocardial Infarction (UA/NSTEMI) 2011 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 CockroftGault formula (Appendix VI, pg 56). Drug doses should be 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 fondaparinux seem to be associated with less bleeding than heparin or enoxaparin 45,91. A recent meta-analysis showed that patients with CKD 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)
I, B
I, B
IIa, B
Table 6: Dosages of Anti-thrombotics in CKD* Table 6: Dosages of Anti-thrombotics in CKD* LOADING DOSE LOADING DOSE UFH UFH Enoxaprin Enoxaprin No change No change 30 mg IV 30 mg IV MAINTENANCE DOSE MAINTENANCE DOSE
No change No change 1 mg/kg sc every 24 hours if 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 Cl<<50 50 ml/min Cr ml/min 36 Tirofiban IV 0.4 mcg/kg/min mcg/kg/min IV IVinfusion infusion 0.05 mcg/kg/min Tirofiban IV infusion infusion 0.4 0.05 mcg/kg/min if if for CrCl Cl<30 <30 ml/min for 30 30 mins mins Cr ml/min ** Modified for the theManagement Management of Patients with UA/NSTEMI. Modifiedfrom fromACC/AHA ACC/AHA 2007 2007 Guidelines Guidelines for of Patients with UA/NSTEMI.
JJ Am Coll Am CollCardiol Cardiol2007; 2007; 50:1-157. 50:1-157.
9.4 9.4
UA/NSTEMI UA/NSTEMI in in Diabetes Diabetes
94,95 Diabetics mortality followingan anACS ACS94,95 . The Diabetics have have an an increased mortality following . The 35 glucose has been been shown shown to to be beaasignificant significant glucose level level at at admission admission has
Fondaparinux Avoid if Cr Cl < 30 ml/min Avoid if Cr Cl <mcg/kg/min 30 ml/min if Eptifibatide 180 mcg/kg IV Infusion 1.0 Eptifibatide 180 mcg/kg IV Infusion 1.0 mcg/kg/min if Clinical Practice Guidelines on Cr Cl < 50 ml/min Cr Cl < 50 ml/min Tirofiban IV infusion 0.4 mcg/kg/minAngina/Non IV infusion 0.05 mcg/kg/min if management of Unstable ST Tirofiban IV mcg/kg/min IV infusion 0.05 mcg/kg/min if for infusion 30 mins0.4 Cr Cl <30 ml/min Elevation Myocardial Infarction (UA/NSTEMI) 2011 for 30 mins Cr Cl <30 ml/min * Modified from ACC/AHA 2007 Guidelines for the Management of Patients with UA/NSTEMI. * Modified from ACC/AHA 2007 Guidelines for the Management of Patients with UA/NSTEMI. J Am Coll Cardiol 2007; 50:1-157.
J Am Coll Cardiol 2007; 50:1-157.
9.4 9.4
UA/NSTEMI in Diabetes UA/NSTEMI in Diabetes Diabetics have an increased mortality following an ACS 94,95 94,95. The Diabeticslevel haveat an increased has mortality an ACS . The glucose admission been following shown to be 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 96,97 predictor of 1 year mortality with a predictive value equivalent to LV systolic dysfunction . systolic dysfunction 96,97. Diabetics should be treated aggressively with: Diabetics should be treated aggressively with:
I, B I, B IIb, B IIb, B I, A I, A
Antiplatelet agent aspirin and clopidogrel or prasugrel. Antiplatelet agent aspirin and or prasugrel. Prasugrel has been found to be clopidogrel more effective in diabetics 31 31. . a Prasugrel has been found to be more effective diabetics GP IIb/IIIa inhibitors a contemporary trial in indicated only GP IIb/IIIa inhibitors a contemporary trial indicated only a modest reduction in adverse events 98,99 . . however at higher risk modest reduction in adverse events 98,99 Early invasive approach diabetics are 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 is still a lack of consensus on the optimal management blood during the acute event. Intensive insulin therapy of to blood sugars during theinacute event. Intensive insulin therapy to achieve normoglycemia the acute setting has not been shown to achievemortality normoglycemia in the acute setting has not in been to reduce and is associated with an increase the shown episodes reduce mortality 100 and is associated with an increase in the episodes of hypoglycemia 100. A general consensus is to keep blood sugars of hypoglycemia A the general consensus is to keep blood sugars less than 8mmol/l .in acute setting and then aim for optimal less than 8mmol/l in the acute setting and then aim for optimal control following 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 phase of of UA/NSTEMI usually STEMI 1 to 3 months. The risk acute of recurrence ischaemic is events, or death is risk of during recurrence of ischaemic events, STEMI or death is highest this period. Following this, most patients assume highest during this period. this, most patients assume a clinical course similar toFollowing that of patients with chronic stable a clinical course similar to that of patients with chronic stable angina. angina. Several lifestyle modification measures and drug therapies have Several lifestyle and drug therapies have been shown to modification be effective measures in improving long-term outcome. been shown to be effective in improving long-term outcome. However they are underutilized. Therefore health care providers 37 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)
36
I, B I, B
10.1.1 Antiplatelet agents

I, A
ASA should be prescribed at 75-150 mg daily unless
proper and safe use. Clinical Practice Guidelines on lifestyle change and CV risk factors modification
Patients given sublingual nitrates should be instructed in its
management of Unstable Angina/Non ST scheduling of timely follow-up appointment and dates for Elevation Myocardial Infarction (UA/NSTEMI) 2011 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. 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 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. 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 implantation is for 6 to 12 months or longer 103. There are no recent clinical trial data on the use of triflusal in ACS.
I, A
I, A
I, A
I, C
10.1.2 -blockers (see section 7.2.4.2)

I, B
-blockers should be continued for patients with ischemia unless contraindicated. Long term treatment following UA/NSTEMI may lead to significant mortality reduction104. -blockers should be continued indefinitely in patients with 38 reduced LV function, with or without symptoms of heart failure105,106.
I, B I, A
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. More aggressive lipid lowering further lowers cardiovascular event rates 110. Lipid management includes:
37
I, A
I, C
Assessment of a fasting lipid profile for all patients, within 24
Practice Guidelines Clinical -blockers should be continued indefinitely in on patients with

reduced LV function, with or without symptoms of heart management of Unstable Angina/Non ST 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. More aggressive lipid lowering further lowers cardiovascular event rates 110. Lipid management includes:
I, A
I, C
Assessment of a fasting lipid profile for all patients, within 24 hours of hospitalization. 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. LDL-C level should be targeted <2.0 mmol/L for most patients 111,112 . Patients with low HDL-C may benefit from fibrates or nicotinic acid 113,114.
I, A
I, A I, B
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. For all other patients ACE-Is should be considered to prevent recurrence of ischaemic events 121-124. 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.
IIa, A
IIa, A
39
38
Table Table 7: 7: Recommended Recommended dosages dosages of of ACE-I ACE-I in in UA/NSTEMI UA/NSTEMI Table 7: Recommended dosages of ACE-I in UA/NSTEMI Type Initiation Target Type Initiation dose dose Target dose dose Type Initiation dose Target dose Captopril 6.25 mg bd-tds 25-50 mg Captopril 6.25 mg bd-tds 25-50 mg tds tds Captopril 6.25 mg bd-tds 25-50 mg tds Ramipril 2.5 mg bd 10 mg od Ramipril 2.5 mg bd 10 mg od Ramipril 2.5 mg bd 10 mg od Enalapril 2.5-5 mg od 20 mg bd Enalapril 2.5-5 20 Enalapril 2.5-5 mg mg od od 20 mg mg bd bd Enalapril 2.5-5 mg od 20 mg bd Lisinopril 5 mg od 40 mg od Lisinopril 5 mg od 40 mg od Lisinopril 5 mg od 40 mg od Lisinopril 5 mg od 40 mg od Perindopril 2-2.5 mg mg od od 8-10 mg mg od Perindopril 2-2.5 8-10 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 Blockers (ARBs) (Table 8, pg 39) 10.1.5 Angiotensin-Receptor Angiotensin-Receptor Blockers Blockers (ARBs) (ARBs) (Table (Table 8, 8, pg 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, ARBs be substituted 125-127 be I, A A ARBs should should substituted for for patients patients with with ACE-I ACE-I intolerance 125-127. I, A ARBs should substituted for patients with ACE-I 125-127. be 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 in in UA/NSTEMI UA/NSTEMI Table 8: Recommended dosages of ARB in UA/NSTEMI Type Initiation dose Target dose Type Initiation Target Type Initiation dose dose Target dose dose Type Initiation dose Target dose Valsartan 40-80 mg od 160 mg od Valsartan 40-80 mg od 160 mg Valsartan 40-80 mg od 160 mg od od Valsartan 40-80 mg od 160 mg od 10.1.6 Aldosterone receptor antagonist 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 blockade be considered Long-term aldosterone receptor blockade should betreated considered in patients aldosterone who are inreceptor heart failure and should already with I, B I, B Long-term aldosterone receptor blockade should betreated considered in patients are heart failure and ACE-I and who -blockers. These spironolactone and in patients who are in in heartagents failureinclude and already already treated with with I, B in patients who are in heartagents failureinclude and already treated with 128,129 ACE-I and -blockers. These spironolactone and . epleronone ACE-I and -blockers. These agents include spironolactone and 128,129 ACE-I and -blockers. These agents include spironolactone and . epleronone . epleronone 128,129 128,129 Care should be .taken in patients with renal dysfunction and epleronone Care hyperkalaemia. Care should should be 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 anginals Therapy are not required for patients with successful 10.1.7 Anti Anti Anginal I, C Anti anginals not for revascularization and no required residual ischaemia. Anti anginals are are not required for patients patients with with successful successful I, I, C C Anti anginals are not required for patients with successful revascularization and no residual ischaemia. I, C revascularization and no residual ischaemia. 10.2 Follow-up investigations (Fig 1, pg 5) revascularization and no residual ischaemia. 10.2 Follow-up investigations (Fig 1, pg 5) 10.2 Follow-up pg UA/NSTEMI 5) In the outpatient investigations evaluation of (Fig low 1, risk patients, the 10.2 Follow-up investigations (Fig 1, pg 5) following investigations maybe considered: In the outpatient evaluation of low risk UA/NSTEMI In the outpatient evaluation of low risk UA/NSTEMI patients, patients, the the In the outpatient evaluation of low risk UA/NSTEMI patients, the following investigations maybe considered: following investigations maybe considered: Echocardiogram to assess LV function following investigations maybe considered: Treadmill stress test Echocardiogram to LV Echocardiogram to assess assess LV function function Stress echocardiogram treadmill or pharmacological stress Echocardiogram to assess LV function Treadmill stress test Treadmill stress test Nuclear perfusion study Treadmill stress test Stress echocardiogram treadmill or pharmacological stress Stress echocardiogram treadmill or pharmacological stress MRI stress MRI for ischaemia and perfusion MRI for viability Stress echocardiogram Nuclear perfusion Nuclear perfusion study study treadmill or pharmacological stress 40 Nuclear perfusion study MRI MRI ischaemia MRI stress stress MRI for for ischaemia and and perfusion perfusion MRI MRI for for viability viability MRI stress MRI for ischaemia and 40perfusion MRI for viability
39
40 40
Low risk patients with significant demonstrable ischaemia and all Low risk with significant demonstrable ischaemia and Low risk patients patients significant demonstrable ischaemia and all all intermediate/high riskwith patients should be considered for revascularization. intermediate/high intermediate/high risk risk patients patients should should be be considered considered for for revascularization. revascularization. Key messages Key Key messages messages Patients should be Patients should be on on optimal optimal medical medical therapy therapy at at discharge. discharge. This This I,A be on optimal medical therapy at discharge. This Patients should I,A, clopidogrel (for at least a month and ideally for includes ASA includes ASA I,A, clopidogrel (for at least a month and ideally for I,B I,B at least a I,C I,A ideally for I,B includes ASA clopidogrel (for month and I,B + CCBs I,C, ACE-I I,A or ARB I,B at least least a a year) ,I,B , -blockers at year) I,B, -blockers I,B + CCBs I,C, ACE-I I,A or ARB I,B I,A at least a year) , -blockers + CCBs , ACE-I or ARB I,A. (Table 1, pg 4) and statins 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 I,C These drugs should be doses uptitrated I,C. during outpatient visits to the recommended tolerated recommended tolerated doses I,C. recommended tolerated doses . Low Low risk risk patients patients should should be be assessed assessed non-invasively non-invasively for for Low risk I,C patients should be assessed non-invasively for I,C ischaemia . (Fig 1, pg 5) ischaemia . (Fig 1, pg 5) I,C 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% the patient. It .has been reduce mortality by 130-132 approximately There wasshown also a to trend towards reduction 130-132 133reduction There was also a towards approximately 20%-25% . MI over a .median follow-up oftrend 12 months in non-fatal recurrent in non-fatal recurrent MI over a median follow-up of 12 months 133.
11.1 11.1 Cardiac rehabilitation programs include: Cardiac rehabilitation programs include: Counselling and educating the patient and family members on CAD Counselling and educating the patient and family members on CAD Beginning an exercise program Beginning an exercise program Helping the patient modify risk factors such as high blood pressure, Helping the patient modify risk factors such as high blood pressure, smoking, high blood cholesterol, physical inactivity, obesity and smoking, high blood cholesterol, physical inactivity, obesity and diabetes diabetes Providing vocational guidance to enable the patient to return to work Providing guidance to enable the patient to return to work Supplying information on limitations Supplying vocational information on physical physical limitations Supplying on physical limitations Educating and compliance to Educating information and ensuring ensuring compliance to medications medications Educating and ensuring compliance to medications Providing support Providing emotional emotional support Providing emotional support Cardiac Cardiac rehabilitation/secondary rehabilitation/secondary prevention prevention programs programs are are generally generally Cardiacinto rehabilitation/secondary prevention programs are generally divided 3 divided into 3 main main phases: phases: 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): a a program program that that Phase 1: Inpatient CR known as Phase to 1 CR): a program that delivers preventive and rehabilitative services hospitalized patients delivers preventive and (also rehabilitative services to hospitalized patients following ACS delivers and rehabilitative services to hospitalized patients followingpreventive ACS following ACS Phase Phase 2: 2: Early Early outpatient outpatient CR CR (also (also known known as as Phase Phase 2 2 CR): CR): generally generally within first 3outpatient but continuing upPhase Phase 2: Early CR (also known as 2 CR): generally within the the first 3 to to 6 6 months months but continuing up to to 1 1 year 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
Clinical Practice Guidelines on management of Unstable Angina/Non ST Elevation Myocardial Infarction (UA/NSTEMI) 2011 Phase 3: Long-term outpatient CR (also known 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 3060 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 -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 GTNs or if there is a change in the usual pattern of angina, they should go to the nearest health facility.
42
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121. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double blind, placebocontrolled, 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-enzymeinhibitors 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 : 234244. 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
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APPENDIX I: Braunwalds Classification of Unstable Angina* CLINICAL CIRCUMSTANCES A Severity Develops in Presence of Extracardiac Condition That Intensifies Myocardial Ischemia (Secondary UA) B Develops in Absence of Extracardiac Condition (Primary UA) C Develops Within 2 weeks of MI (Postinfarction UA)
INew onset of severe angina or accelerated angina; no rest pain IIAngina at rest within past month but not within preceding 48 hours (angina at rest, subacute) IIIAngina at rest within 48 hours (angina at rest, acute)
IA
IB
IC
IIA
IIB
IIC
IIIA
IIIB-Tneg IIIB-Tpos
IIIC
UA : Unstable angina; T : Troponins

*Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation. 2000 ;102 :118-22.
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Appendix Elevationsof of cardiac cardiac troponin in the absence of of Appendix II:II: Elevations troponin in the absence overt ischaemic ischaemic heart disease* overt heart disease* Damage related secondary myocardial ischaemia (MI type 2) 2) Damage related to to secondary myocardial ischaemia (MI type
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, e.g. systemic without lupus erythematosus, syndrome Coronary endothelial dysfunction significant CAD, Kawasaki e.g. cocaine abuse Coronary endothelial dysfunction without significant CAD, e.g. cocaine abuse
Damage not related to myocardial ischaemia
Tachy- or bradyarrhythmias
Damage not related to myocardial ischaemia

Cardiac contusion Cardiac incisions with surgery Cardiac 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 syndrome Peripartum cardiomyopathy Severe pulmonary embolism or pulmonary hypertension Renal failure Severe acute neurological diseases, e.g. stroke, trauma Peripartum cardiomyopathy Infiltrative Renal failure diseases, e.g. amyloidosis, sarcoidosis Extreme exertion Severe acute 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 K, Mair J,Katus H et al for Study Group on Biomarkers in Cardiology of the ESC Frequent defibrillator shocks
*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
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
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Appendix AppendixIII: III: Likelihood Likelihood That That Signs and Symptoms SymptomsRepresent Representan anACS ACS secondary secondary to CAD CAD Greater GreaterLikelihood Likelihood History History Chest Chestor orleft leftarm armpain pain or or discomfort discomfort as chief chiefsymptom symptomreproducing reproducing prior prior documented documentedangina angina Known Knownhistory historyof of CAD, CAD, including including MI 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, diaphoresis, diaphoresis,pulmonary pulmonary edema, edema, or rales Extracardiac Extracardiacvascular vascular disease disease ECG ECG New, New,or orpresumably presumably new, new, transient transient STT-wave T-wave attening atteningor orinversion inversion segment segmentdeviation deviation (1 (1 mm mm or or greater) greater) or T- less less than than 1 1mm mmin inleads leadswith with wave waveinversion inversionin in multiple multiple pre-cordial pre-cordial dominant dominant R Rwaves waves leads leads Normal ECG ECG Normal Cardiac CardiacBiomarkers Biomarkers Elevated Elevatedcardiac cardiacTnI, TnI, TnT, TnT, or or CK-MB markers markers Normal Normal Chest discomfort discomfortreproduced reproduced Chest by palpation palpation by Chest pains painsin inthe theabsence absenceof of Chest any of of the the greater greaterlikelihood likelihood any characteristics characteristics Recent cocaine cocaineuse use Recent Lower Likelihood Likelihood Lower
Modified Modifiedfrom fromBraunwald BraunwaldE, E, et et al. al. Unstable Unstable Angina: Diagnosis Diagnosisand andManagement. Management. 1994;3-11994;3-1AHCPR AHCPR Publication PublicationNo No94-0602:1-154. 94-0602:1-154.
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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 Age y factors or older At least 3 65 risk for CAD ( family history of premature CAD, At least 3 risk factors for CAD (active familysmoker, history of premature CAD, hypertension,elevated cholesterols, diabetes) hypertension,elevated cholesterols, active smoker, diabetes) Known CAD (coronary stenosis of > 50%) Known CAD (coronary stenosis of > 50%) Use of aspirin in prior 7 days Use of aspirin in prior 7 days ST-segment deviation (>0.5mm) on ECG ST-segment deviation in (>0.5mm) At least 2 anginal episodes prior 24 on h ECG At least 2 anginal episodes in Elevated serum cardiac biomarkersprior 24 h Elevated serum cardiac biomarkers Total Score = 7 points Total Score = 7 points Low Risk : < 2 point 2 point Low Risk < points Moderate Risk: :3-4 : 3-4 points HighModerate Risk : >5Risk points High Risk : >5 points
Adapted from : Adapted Antmanfrom EM,: Cohen M, Bernink PJ, et al. The TIMI risk score for unstable
Antman EM, Cohen Bernink et al. The and TIMI risk score for unstable angina/non-ST elevation MI: M, a method forPJ, prognostication therapeutic decision angina/non-ST elevation MI: making. JAMA 2000; 284 : 835 42 a . method for prognostication and therapeutic decision making. 2000; 284Giugliano : 83542 . RP, et al. Implications of upstream Sabatine MS,JAMA Morrow DA, Sabatine MS, inhibition Morrow DA, al. Implications of upstream glycoprotein IIb/IIIa and Giugliano coronary RP, arteryet stenting in the invasive glycoprotein IIb/IIIa inhibition and stenting in the invasive management of unstable angina/non STcoronary elevationartery myocardial infarction. A management of unstable in angina/non elevation myocardial infarction. A comparison of the Thrombolysis Myocardial ST Infarction (TIMI) IIIB trial and the comparison of the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial and Treat angina with Aggrastat and determine Cost of Therapy with Invasive or the Treat angina with Aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 trial. Circulation 2004; 109 : 874-880. Conservative Strategy (TACTICS)-TIMI 18 trial. Circulation 2004; 109 : 874-880.
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APPENDIX V: V: GRACE PREDICTION SCORE CARD AND AND NOMOGRAM APPENDIX GRACE PREDICTION SCORE CARD NOMOGRAM FOR ALL CAUSE MORTALITY FROM DISCHARGE TO 6 TO 6 FOR ALL CAUSE MORTALITY FROM 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.
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APPENDIX APPENDIX VI: VI Calculation : Calculation Of Creatinine Of Creatinine Clearance Clearance APPENDIX APPENDIX VI: Calculation VI: Calculation Of Creatinine Of Creatinine Clearance Clearance Estimated Estimated GFR GFR (ml/min) (ml/min) = (140-age) = (140-age) x weight x weight or or 1.2 (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 SCr x [mol/L SCr [mol/L ]) ]) SCr [mol/L SCr [mol/L ] ] ]) [mol/LS ]) SCr ] [mol/L ] (0.814 x S(0.814 x SCr Cr [mol/L Cr [mol/L SCr : S serum creatinine creatinine Cr : serum SCr : serum Screatinine Cr : serum creatinine For women For women multiply multiply by 0.85 by 0.85 For women For multiply women by multiply 0.85 by 0.85 Severity Severity Of CKD* Of CKD* Severity Of Severity CKD* Of CKD* SEVERITY SEVERITY OF CKD OF CKD CREATININE CREATININE CLEARANCE CLEARANCE SEVERITY SEVERITY OF CKD OF CKD CREATININE CREATININE CLEARANCE CLEARANCE Normal Normal to mild to mild >60 >60 ml/min ml/min Normal toNormal mild to mild >60 ml/min >60 ml/min Moderate Moderate 30-59 30-59 ml/min ml/min Moderate Moderate 30-59 ml/min 30-59 ml/min Severe Severe <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 disease: disease: evaluation, evaluation, classification, classification, and and stratification. stratification. Am Am Jchronic Kidney J Kidney * kidney National *Kidney National Foundation. Kidney Foundation. K/DOQI clinical K/DOQI practice clinical guidelines practice guidelines for for chronic Dis.2002; Dis.2002; 39 (suppl 39evaluation, (suppl 1): S1 1): S226 S1 S226 kidney disease: kidney disease: evaluation, classification, classification, and stratification. and stratification. Am J Kidney Am J Kidney Dis.2002; 39 Dis.2002; (suppl 1): 39S1 (suppl S226 1): S1S226
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 Classification ACC/ESC ACC/ESC Classification Classification Contrast Contrast Agent Agent - Isomolar - Isomolar agent agent I, A I, A Contrast Agent Contrast Agent - Low - Low osmolar osmolar agents agents IIa, IIa, B I, A - Isomolar -agent Isomolar agent I, A B - use use minimal minimal volume volume - Low osmolar - Low agents osmolar agents IIa, I, B C I, C IIa, B - use minimal - use volume 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 Saline Saline Infusion Infusion I, C I, C Saline Infusion Saline Infusion I, C I, C Sodium Sodium Bicarbonate Bicarbonate IIa, B IIa, B Sodium Bicarbonate Sodium Bicarbonate IIa, B IIa, B Acetylcysteine Acetylcysteine IIb, B IIb, B Acetylcysteine Acetylcysteine IIb, B IIb, B
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APPENDIX VIII: Prevention ofof Contrast Induced Nephropathy APPENDIX VIII: Prevention Contrast Induced Nephropathy
AGENT AGENT CONCENTRATION DOSE DOSE / FLOW RATE CONCENTRATION / FLOW RATE Rate 1.0-1.5 ml/kg/hrfor for Rate ofof 1.0-1.5 ml/kg/hr 3h-12h before and 6h-24h 3h-12h before and 6h-24h after the procedure ensuring after the procedure ensuring urine flow rate of 150 aa urine flow rate of 150 ml/hour ml/hour Reduce rate to 0.5 ml/kg/hrifif Reduce rate to 0.5 ml/kg/hr LVEF<40% LVEF<40% 3 ml/kg/hr for 1 hour before 3 ml/kg/hr for 1 hour before the contrast followed by an the contrast followed by an infusion of 1 ml/kg/hr for 6 infusion of 1 ml/kg/hr for 6 hours after the procedure hours after the procedure
Sodium Chloride* 0.9% 0.9% solution Sodium Chloride* solution
Sodium Sodium Bicarbonate** Bicarbonate**
NN-acetylcysteine*** acetylcysteine***
154 mEq/L in 5% 154 mEq/L in 5% dextrose in water dextrose in water (154 ml of (154 ml of 1000 mEq/l of 1000 mEq/l of sodium bicarbonate sodium + 850 bicarbonate ml of 5% + 850 ml of 5% Dextrose) Dextrose)
1200 mg twice daily, one day 1200 mgand twice daily, before one day one afterday the before and one day after the contrast contrast
2006; 692 9. isosmolar iodixanol compared with low-osmolar contrast media. J Am Coll Cardiol. 48: 2006; 6929. ** Briguori C, Colombo A, Violante A et al. Standard vs double dose of N-acetylcysteine to prevent contrast agent Eur J 2004; : 206-211. C, Colombo A,associated Violante Anephrotoxicity. et al. Standard vsHeart double dose 25 of N-acetylcysteine to ** Briguori 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-contrastin renal functionC by J Med. 2000; 343: Tepel M, Vanreductions der Giet M, Schwarzfeld etacetylcysteine. al. Prevention N ofEngl radiographic-contrast*** agent-induced 180184. agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000; 343: 180184.
* McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media. J of Am Coll Cardiol. PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis the renal safety 48: of * McCullough
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ACKNOWLEDGMENTS ACKNOWLEDGMENTS The committee of this guideline would like to express their gratitude and The committee of this guideline would like to express their gratitude and appreciation to the following for their contribution: appreciation to the following for their contribution: Technical Advisory Committee, Clinical Practice Guidelines, Ministry of Technical Committee, Clinical Practice Guidelines, Ministry of Health for Advisory their valuable input and feedback Health for their valuable input and feedback Panel of external reviewers who reviewed the draft Panel of external reviewers reviewed the draft Secretarial assistance from who 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 This CPG was (M) made possible Sanofi-Aventis Sdn Bhd. Sanofi-Aventis (M) Sdn content of this guideline. Bhd. content of this guideline.
by an unrestricted educational grant from by an unrestricted grant from The funding body educational did not influence the The funding body did not influence the
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Medical therapy* * This includes aspirin +

Risk stratify as outpatient (Fig1, pg 5)

I,C or, Ticlopidine IIa,B IIa,B

+ UFH or, LMWH or, fondaprinux or, Bivalirudin + -blockers

I,A I,A I,A

I,A 1,B I,B

I,A + ACE-I I,A I,A

IIa, A or ARB + Statins I,B I, A I,B I,A

+/- calcium channel blockers +/- nitrates

1,B IIa,C I,C

I,B IIa,C I,C

Figure 1: Non-invasive investigation of Low Risk Patients with UA/NSTEMI*

Normal ECG, Good Exercise Tolerance

Exercise stress test

Equivocal / Positive Test

Risk Factor Reduction + Medical Therapy for CAD

* Low risk patients have :

Congratulations and a personal toast to Malaysian heart health!

amalar Dr.Rajadurai Jeyamalar Rajadurai

mad Nizar Dr. Ahmad Nizar

uar Rapaee Dr. Anuar Rapaee Chandran Dr. Aris Chandran

ar Ismail Dr. Omar Ismail

h Maskon Dr. Oteh Maskon

e Raman Dr. Sree Raman

Kui Dr. Hian Sim Kui Hian

n Azman Dr. Wan Azman

bayaah Dr.Zambahari Robayaah Zambahari

Dr. Chan Hiang Dr. Chan Chuan Hiang Chuan

Dr. Jeyaindran Dr. Jeyaindran Sinnadurai Sinnadurai

Dr. Lee Chuey Dr. Lee Yan Chuey Yan

Dr. Lee Fatt Dr. Soon Lee Fatt Soon

Dr. Kim Tan Dr. Kim Tan

Dr. V Paranthaman Dr. V Paranthaman

Dr. Santha Dr. Kumari Santha Kumari

Consultant Consultant Physician Physician Hospital Sultanah HospitalRahimah SultanahKelang Rahimah K

Dr. Tee Lian Dr.Kim Tee Lian Kim

Dr. Wong Kai Dr. Wong Fatt Kai Fatt

Dr. Zurkarnai Dr. Yusof Zurkarnai Yusof

4.4. Cardiac Biomarkers

however be used as the only biomarker to identify patients with NSTEMI.

FIGURE 3: Time course of elevation of serum cardiac biomarkers in ACS

Key message: Key message:

Clinical Practice Guidelines on

with symptoms or need for a pacemaker. There was also a

Bivalirudin UA/NSTEMI During PCI

Fondaparinux UA/NSTEMI During PCI

* For doses in renal impairment see section 9.3, Table 6, pg 35

Nitrates (Table 3, pg 29)

-blockers (Table 4, pg 29)

Table 3: Recommended dosages of Nitrates in UA/NSTEMI*

Nitroglycerine, Glyceryl trinitrate Nitroglycerine, Glyceryl trinitrate

Intravenous GTN Spray

GTN Spray Transdermal patch

Isosorbide Isosorbide dinitrate mononitrate

then hours off 10 on, 20 mg,12 2 3 times daily 2 12 mg / hour

Initiation dose 25 mg od 25 mg mg od bd 1.25 25 mg 3.125 mg od bd 1.25 mg od 3.125 mg bd

Target 100 mg dose od 100 mg 10 mg odbd 100 mg 25 mg bdod 10 mg od 25 mg bd

Clinical Guidelines UA/NSTEMI in Practice Chronic Kidney Disease (CKD) on

UA/NSTEMI UA/NSTEMI in in Diabetes Diabetes

10.1.1 Antiplatelet agents

ASA should be prescribed at 75-150 mg daily unless

Sodium Sodium Bicarbonate Bicarbonate