CPG Ua-Nstemi 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 the Expert Panel Members of the Expert Panel
erson: Chairperson: Consultant Cardiologist, Consultant Cardiologist, Sime DarbySime Darby Medical Center Medical Center Subang Jaya, Selangor Selangor Subang Jaya,
amalar Rajadurai Rajadurai Dr. Jeyamalar
Members ers (in alphabetical order) Members (in alphabetical order) (in alphabetical order)
Consultant Cardiologist, Consultant Cardiologist, Sime DarbySime Darby Medical Center Medical Center Subang Jaya,Selangor Subang Jaya,Selangor Consultant Cardiologist, Consultant Cardiologist, Hospital Serdang Serdang Hospital Consultant Physician, Physician, Consultant Hospital Sultanah Bainun, Ipoh Hospital Sultanah Bainun, Ipoh Consultant Cardiologist, Consultant Cardiologist, Hospital Besar Pulau Pinang Hospital Besar Pulau Pinang Consultant CardiologistCardiologist Consultant Hospital UKM, KualaUKM, Kuala Lumpur Hospital Lumpur
mad Nizar Dr. Ahmad Nizar
uar Rapaee Dr. Anuar Rapaee Chandran Chandran Dr. Aris
ar IsmailOmar Ismail Dr.
h Maskon Dr. Oteh Maskon
e Raman Dr. Sree Raman
Consultant Physician, Physician, Consultant Hospital Tuanku Jaafar, Seremban Seremb Hospital Tuanku Jaafar, (HTA trained) (HTA trained)
Kui Dr. Sim Kui Hian Hian
Consultant Cardiologist, Consultant Cardiologist, Sarawak General Hospital,Kuching Sarawak General Hospital,Kuchi
n Azman Dr. Wan Azman
Consultant Cardiologist, Consultant Cardiologist, University Malaya Medical Center University Malaya Medical Cente Consultant Cardiologist, Consultant Cardiologist, Institute Jantung Negara, Institute Jantung Negara, Kuala Lumpur Kuala Lumpur
bayaah Zambahari Zambahari Dr. Robayaah
External Reviewers (in alphabetical order): External Reviewers (in alphabetical order): order): External Reviewers (in alphabetical
Dr. Chan Hiang Chuan Dr. Chan Hiang Chuan
Consultant Physician Physician Consultant Sarawak General Hospital,Kuching Sarawak General Hospital,Ku Consultant Physician Physician Consultant Head of Internal of Internal Medicine, Head Medicine, Ministry Of Health, Of Health, Ministry Hospital Kuala Lumpur Lumpur Hospital Kuala
Dr. Jeyaindran Sinnadurai Dr. Jeyaindran Sinnadurai
Dr. Lee Chuey Yan Dr. Lee Chuey Yan
Consultant Cardiologist Consultant Cardiologist Hospital Sultanah Aminah Johor Hospital Sultanah Aminah Joh Consultant Geriatrician Consultant Geriatrician Hospital Kuala Lumpur, KL Hospital Kuala Lumpur, KL Consultant Cardiologist, Consultant Cardiologist, Sunway Medical Center, Center, Sunway Medical Sunway,Selangor Sunway,Selangor Family Medicine Specialist,Specialist, Family Medicine Klinik Kesihatan Kesihatan Jelapang, Klinik Jelapang, Ipoh, Perak Ipoh, Perak
Dr. Lee Fatt Soon Fatt Soon Dr. Lee
Dr. Kim Tan Kim Tan Dr.
Dr. V Paranthaman Dr. V Paranthaman
Dr. Santha Kumari Kumari Dr. Santha
Consultant Physician Physician Consultant Hospital Sultanah Rahimah Kelang K Hospital Sultanah Rahimah
Dr. Tee Lian Kim Lian Kim Dr. Tee
General Practitioner, General Practitioner, Klinik Young, Newton and Partners Par Klinik Young, Newton and Kuala Lumpur/Petaling Jaya Kuala Lumpur/Petaling Jaya General Practitioner, General Practitioner, LW Medical Associates LW Medical Associates Kuala Lumpur Lumpur Kuala
Dr. Wong Kai Wong Kai Fatt Dr. Fatt
Dr. Zurkarnai Yusof Dr. Zurkarnai Yusof
Consultant Cardiologist Consultant Cardiologist Hospital Universiti Sains Malaysia Malay Hospital Universiti Sains Kota Baru,Kota Baru, Kelantan 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 may present in the the ECG, whereas UA UA In NSTEMI, changes may be be present in ECG, whereas in in In NSTEMI, ST/T changes may be present in the ECG, whereas in UA they theyusually absent and and even if they present, are are usually transient. are are usually absent even if they are 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 AnbeArmstrong PW et al.et al. ACC/AHA Guidelines Adapted with modification from Antman EM, DT, DT, Armstrong PW ACC/AHA Guidelines for the management of patients with ST Elevation Myocardial Infarction at www.acc.org for thefor the management of patientsST Elevation Myocardial Infarction at www.acc.org management of patients with with ST Elevation Myocardial Infarction at www.acc.org
3. PATHOGENESIS 3. PATHOGENESIS 3. PATHOGENESIS ACS occurs due to atherosclerotic plaque rupture, fissure or ulceration ACS ACS occurs dueatherosclerotic plaque rupture, fissure or ulceration occurs due to to atherosclerotic plaque rupture, fissure or ulceration with superimposed thrombosis and coronary vasospasm. Depending on with with superimposed thrombosis and coronary vasospasm. Depending on superimposed thrombosis and coronary vasospasm. Depending on the acuteness, degree of occlusion and the presence of collaterals, the acuteness, degree of occlusion the presence of of collaterals, the acuteness, degree of occlusion and and the presence collaterals, patients can present as UA, NSTEMI or STEMI. patients can present as NSTEMI or STEMI. patients can present as UA, UA, NSTEMI or STEMI. The aetiology of the plaque fissure or rupture is still unclear. Possible The The aetiologythe plaque fissure or rupture is still still unclear. Possible aetiology of of the plaque fissure or rupture is 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. occurring de novo is called Primary UA/NSTEMI. smoking. ACSACS occurring de novo is called Primary UA/NSTEMI. Occasionally UA/NSTEMI is secondary to a precipitating condition, which Occasionally UA/NSTEMI is secondary precipitating condition, which Occasionally UA/NSTEMI is secondary to ato a precipitating condition, which is extrinsic to the coronary arterial bed. This is called secondary is extrinsic to coronary arterial bed. This is is called secondary is extrinsic to the the coronary arterial bed. This called secondary UA/NSTEMI and can occur due to: UA/NSTEMI and can occur to: UA/NSTEMI and can occur due due to: increased myocardial oxygen demand as occurring in fever, increased myocardial oxygen demand occurring in fever, increased myocardial oxygen demand as as occurring in fever, tachycardia and thyrotoxicosis tachycardia thyrotoxicosis tachycardia and and thyrotoxicosis to hypotension reduced coronary blood flow due 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 anaemiahypoxemia reduced myocardial oxygen delivery in anaemia or or hypoxemia Secondary UA/NSTEMI is an important cause of ACS in the elderly. Secondary UA/NSTEMI is an important cause of ACS in elderly. Secondary UA/NSTEMI is an important cause of ACS in the 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 causes for elevated troponins are extremely rare It Non coronary causes for elevated troponins are extremely rare . 17. It may o may myocarditis, acute pulmonary embolism, a dissecting aortic acute occur in acute myocarditis, acute pulmonary embolism, aaneurysm dissecting aortic sometimes in septic shock. and sometimes in heart failure and aneurysm, acute heart failureSevere renal dysfunction ma septic shock. Severe renal dysfunction may also cause is however asso cause raised troponins in the absence of ACS. A raised levelraised troponins in the all cause of ACS. A raised level is however with an increase in absence mortality in these patients. (Appendix 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 Creatinine kinase (CK) necrosis (infarction). They are however, less indicators of myocardial and its MB fraction (CKMB) are also important indicators of myocardial necrosis (infarction). They and however, less sensitive and specific compared to cardiac troponins. CK are CKMB have sensitive half life and hence to more troponins. troponins when a shorter and specific comparedare cardiac useful thanCK and CKMB have a shorter half life and hence are more useful than troponins when diagnosing reinfarction. diagnosing reinfarction. All patients with NSTEMI have raised troponins, however, the CKMB may 18,19 be patients in 10-20% of have raised troponins, however, the CKMB may . A raised CKMB in the All normal with NSTEMI these patients presence of a normal troponin level has no prognostic significance 18,19. in the be normal in 10-20% of these patients 18,19. A raised CKMB 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 onsetnotchest pain. A negative test within 4-8 hours of chest 2 hours Myoglobin is of cardiac specific. It can be detected as early as pain is useful onset of chest pain. A negative test within 4-8 hours of chest pain after the in ruling out myocardial necrosis (infarction). It should not however bein ruling the only biomarker necrosis (infarction). It should not is useful used as out myocardial to identify patients with NSTEMI.
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 4.5 Other diagnostic modalities of the new definition of myocardial infarction. John K French, 4.5 Other diagnostic modalities 2004;90:99106) Harvey D White; Heart
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 and prognostic significance I,A. 19 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 ACUITY HORIZONS-AMI24 Bleeding Risk Score CRUSADE Bleeding Risk Score25 CRUSADE Bleeding Risk Score25 These scores are calculated based on age, clinical status and These scores are calculated based on age, clinical status and hemodynamics at presentation, serum creatinine and hematocrit level and hemodynamics at presentation, serum creatinine and hematocrit level and the use and combinations of antiplatelets and anticoagulants. the use and combinations of antiplatelets and anticoagulants. Key messages Key messages Risk stratification is important for prognosis and to guide Risk stratification is important for prognosis and to guide management I,A. management I,A. 6. 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: on the triage: Based If the history is suggestive of ACS : - Give soluble aspirin 300 ACS : If the history is suggestive of mg crushed stat - Give sublingual GTN If the history is suggestive of mg crushed stat soluble aspirin 300 ACS : - Do 12 lead ECGGTN cardiaccrushed stat Give soluble aspirin 300 mg biomarkers sublingual and - Do 12 lead ECGGTN cardiac biomarkers Give sublingual and - Do 12 lead ECG and cardiac biomarkers If the ECG and cardiac biomarkers are suggestive of ACS - Give clopidogrel 300 mg stat if available. If the ECG and cardiac biomarkers are suggestive of ACS -- Give clopidogrel 300 mg stat if are suggestive of where Send the patient biomarkers available. If the ECG and cardiac to the nearest healthcare facility ACS definitive treatment can be given. -- Give clopidogrel 300the nearest healthcare facility where Send the patient to mg stat if available. - Send the treatment can nearest healthcare facility where definitive patient to the be given. definitive treatment can be given. If the ECG and cardiac biomarkers are inconclusive for ACS Low risk patients : they can be referred as outpatient If the- ECG and cardiac biomarkers are inconclusive for ACS for and cardiac biomarkers1, be 5) If the- ECGcardiacpatients : they canare inconclusive for ACS Low risk assessment. (Fig pg referred as outpatient Intermediate / High they patients : - Low risk patients : Risk can be 5) should be admitted for cardiac assessment. (Fig 1, pg referred as outpatient . - for cardiac assessment. (Fig 1, pg 5) should be admitted Intermediate / High Risk patients : - - Intermediate / High Risk patients : should be admitted . 7.2 In-Hospital Management (Table1, pg 4) - . 7.2 In-Hospital Management (Table1, pg 4) 7.2.1 In-Hospital Management (Table1, pg 4) 7.2 Initial management General Measures 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 Highcontinuous ECG monitoring. with risk patients preferably should be admitted to CCU/HDU I, C supplemental oxygen monitoring.given to maintain SpO2 >90%, with continuous ECG should be supplemental oxygen should be given to maintain distress or in patients with left ventricular failure, respiratorySpO2 >90%, I, B supplemental oxygen should be given to in patients risk left ventricular failure, maintain distress or having high with features for hypoxemia. respiratorySpO2 >90%, I, B in patients with features for hypoxemia. respiratory distress or I, B having high risk left ventricular failure, for pain relief, features (intravenous 2 having high riskmorphine for hypoxemia. mg to 5 mg) together IIa,B for concomitant intravenous anti-emetic may be mg) withpain relief, morphine (intravenous 2 mg to 5given.together IIa,B for pain relief, morphine (intravenous 2 mg to 5given.together with concomitant intravenous anti-emetic may be mg) 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 Oral antiplatelet agents Acetylsalicylic acid (ASA) 7.2.2.1 7.2.2.1.1 Acetylsalicylic acid (ASA) Recommended loading dose: I, A 7.2.2.1.1 Acetylsalicylic acid (ASA) 300 mg of soluble/chewable aspirin 26,27. Enteric coated aspirin is not recommended for Recommended loading dose: 300 mg of soluble/chewable I, A initial loading Enteric coatedofaspirin isonset recommended for Recommended loading dose:its slow not of action. 300 mg of soluble/chewable aspirin 26,27. dose because I, A aspirin 26,27. dose because its slow not of action. initial loading Enteric coatedofaspirin isonset recommended for 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 myoCardialneed for a pacemaker. There was also a with symptoms or infarCtion (ua/nstemi) 2011
with symptoms or need for a pacemaker. There was also a
7.2.2.2 Intravenous Antiplatelet Therapy major bleeding 32. (GP) small increase in non CABG related Glycoprotein IIb/IIIa Inhibitors 7.2.2.2 Intravenous Antiplatelet Therapy Glycoprotein (GP) IIb/IIIa These include: Inhibitors Abciximab These include: Tirofiban Abciximab Eptifibatide Tirofiban 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 These agents may prior to in is now no longer practiced 33,34. upstream therapy be usedPCIhigh risk patients awaiting transfer to a PCI facility for an early invasive strategy. Its routine use as 33,34 upstream therapy prior to . 7.2.3. Anticoagulant Therapy PCI is now no longer practiced 7.2.3. Anticoagulant (Table 2, pg 27) These include: Therapy
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 inhibitor-Fondaparinux - It is best used in UA/NSTEMI patients treated conservatively 38,39. - It is associated with an increase in patients treated is best used in UA/NSTEMI catheter-related conservatively 38,39. thrombus and coronary angiographic complications. - It is associated with an increase sole anticoagulant is not recommended as the in catheter-related thrombus and . during PCI 38,39 coronary angiographic complications. - It used in recommendedand the patient requires an If is not UA/NSTEMI as the sole anticoagulant during PCI 38,39. UFH should be given during the invasive strategy, - If used in UA/NSTEMI and the itpatient requireswith procedure. When used in PCI, is associated an invasive strategy, UFH should be given during the lower bleeding rates than LMWH 38,39,40. procedure. When used in PCI, it is associated with 38,39,40 lower bleeding anti Xa inhibitors are undergoing . Presently newer oralrates than LMWH evaluation for ACS. Presently newer oral anti Xa inhibitors are undergoing evaluation for ACS. Anti IIa inhibitors Bivalirudin Anti IIaItinhibitors used as a substitute for heparin in patients may be Bivalirudin with heparin-induced thrombocytopenia (HIT) 41. - It is reasonable as use bivalirudin as an alternative to may be used to a substitute for heparin in patients 41 with heparin-induced inhibitors in patients undergoing UFH and GP IIb/IIIa thrombocytopenia (HIT) . - It is reasonable to use bivalirudin as an alternative to PCI 42-45. - UFH and GP IIb/IIIaless bleeding. It is associated with inhibitors in patients undergoing 42-45 - PCI To date . is not yet available in Malaysia. it - It is associated with less bleeding. - To date it is not yet available in Malaysia. 26
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 5 200 at 5 minute to 3 timesg/min* 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 10 on, then 12 3 times 20 mg, 2 hours off daily 2 12 mg / hour Time of Onset 2 minute Time of Onset 1 2 minute minute 2 1 minute minute
Table 3: Recommended dosages of Nitrates in UA/NSTEMI*

Compound
Nitroglycerine, Glyceryl trinitrate Nitroglycerine, Glyceryl trinitrate
Intravenous GTN Spray
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
10 30-60mg, 2 3 times 20 mg daily, ( 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 ischaemiaRecommended dosages of -blockers in UA/NSTEMI* Table 4: is relieved and the desired haemodynamic response is obtained
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 bd 1.25 mg od 25 mg bd 3.125 mg od 1.25 mg od 3.125 mg bd
Target od 100 mg dose 100 mg 10 mg odbd 100 mg 25 mg bdod 10 mg od 25 mg bd
30
30
29
7.2.4.3 Calcium Channel Blockers (Table30) 5, pg 7.2.4.3 Calcium Channel Blockers pg 5, 7.2.4.3 Calcium Channel Blockers (Table 5, (Tablepg 30)30) Calcium channel blockers (CCB) may be be used UA/NSTEMI Calcium channel blockers (CCB) may used in in UA/NSTEMI in Calcium channel blockers (CCB) may be used in UA/NSTEMI in the in the the following situations: following situations: following situations: Verapamil or diltiazem as an an alternative patients who are not Verapamil or diltiazem as alternative to who are not Verapamil or diltiazem as an alternative to patientsto patients who are not able to tolerate or have contraindication to blockers.48 able to tolerate or who have contraindication to blockers. able to tolerate or who who have contraindication to blockers.48 48 Continuing or or recurring angina despite doses of Continuing recurring angina despite adequate doses of IIa,C IIa,C Continuing or recurring angina despite adequate adequate doses of IIa,C nitrates andand -blockers verapamil, diltiazem,release release nitrates -blockers verapamil, diltiazem, diltiazem, slow release nitrates and -blockers verapamil, slow slow nifedipine andand amlodipine. nifedipine amlodipine. nifedipine and amlodipine. Prinzmetals angina (variant angina) angina) Prinzmetals angina (variant angina) Prinzmetals angina (variant
I, B B I, B I,
Short-acting dihydropyridine CCB should be III, III, Short-acting dihydropyridine CCB should be avoided avoided III, A A A Short-acting dihydropyridine CCB should be avoided
TableTableRecommended dosages of Calcium Channel Blockers in UA/NSTEMI* Table 5: 5: Recommended dosages of Channel Blockers in UA/NSTEMI* 5: Recommended dosages of Calcium Calcium Channel Blockers in UA/NSTEM Drug Drug Drug Diltiazem Diltiazem Diltiazem Dose Dose Dose Immediate release 30-90 Immediate release 30-90 tds Immediate release 30-90 mg tds mg mg tds Slow Slow release 100-200 mg mg od release 100-200 mg od Slow release 100-200 od Verapamil Verapamil Verapamil Immediate release 40-80 Immediate release 40-80 tds Immediate release 40-80 mg tds mg mg tds Slow release 120-240 od Slow Slow release 120-240 mg mg od release 120-240 mg od Amlodipine Amlodipine Amlodipine Nifedipine Nifedipine Nifedipine 2.5-10 mg od 2.5-10 2.5-10 mg od mg od Slow Slow release 30-90 mg mg od release 30-90 mg 30-90 od Slow release od
*As *As stated Malaysia stated in MIMS Malaysia *As stated in MIMSin MIMS Malaysia
7.2.5 Lipid Modifying Drugs 7.2.5 7.2.5 Modifying Drugs Drugs Lipid Lipid Modifying
I, A I, A soon soon admission for UA/NSTEMI can reducereduce adverse adverse A soon after admission for for UA/NSTEMI can reduce major adverse after after admission UA/NSTEMI can major major
Current data indicate early initiation of high dose high dose statin therapy Current data indicate that early initiation of statin therapy Current data indicate that that early initiation of high dose statin therapy
cardiac events due to its pleotropic effects49-54. Patients with ACS cardiac eventsevents its pleotropic effects49-54. Patients .with ACS with ACS cardiac due to due to its pleotropic effects49-54 Patients undergoing PCI, have also also been found to towith the with the undergoing PCI, have been found to found benefit with the undergoing PCI, have also been benefit benefit administration of highhigh dose statins before and 10 days10 days of the the administration of of high dose statins before and within 10 days of administration dose statins before and within within of the procedure 55-57. 55-57. procedure 55-57. procedure
The statinsstatins that have beenin UA/NSTEMI to date to date are: The statins that have been studied in UA/NSTEMI are: date are: The that have been studied studied in UA/NSTEMI to Atorvastatin 80 mg od mg od Atorvastatin 80 mg od Atorvastatin 80 Simvastatin 40 mg od mg od Simvastatin 40 mg od Simvastatin 40
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 A I,
These should be considered early for patients with LV dysfunction These should be considered early for patients with LV dysfunction and diabetes 5555. and diabetes . Key messages Key messages Patients should be treated with optimal medical therapy. Patients should be treated with optimal medical therapy. (Table 1,1, pg 4) (Table pg 4) Nitrates I,CI,C,-blockers I,BI,B+ +CCBs I,CI,Care given for relief ofof Nitrates , -blockers CCBs are given for relief ischemia. ischemia.
I,A Statins I,AI,A Statins and ACE-I (for LV dysfunction, LVEF < < 40%) I,A are and ACE-I (for LV dysfunction, LVEF 40%) are given for prognosis. given for prognosis. 8. Revascularization Strategies 8. Revascularization Strategies
There is a strong rationale for early revascularization in There is a strong rationale for early revascularization in intermediate/high risk patients with UA/NSTEMI 56,57. (Flowchart 1, intermediate/high risk patients with UA/NSTEMI 56,57. (Flowchart 1, pg 3, Appendix IV, pg 54) Contemporary antiplatelet and pg 3, Appendix IV, pg 54) Contemporary antiplatelet and anticoagulant therapies have reduced the early hazard of PCI. anticoagulant therapies have reduced the early hazard of PCI. With increasing procedure experience, technological improvements inWith increasing procedure experience, technologicalanticoagulant PCI and the development of new antiplatelet and improvements in PCI and the is a general trend for early revascularization in regimens there development of new antiplatelet and anticoagulant regimens there is a optimal trend for early these patients following general medical therapy. revascularization in 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 angiography/revascularization for patients with coronary (as soon as possible after hospital presentation) I, B coronary refractory orangiography/revascularization for patients ST recurrent angina associated with dynamic with refractory or failure, angina associated with dynamic ST deviation, heartrecurrent 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(<72 hours) coronary angiography/revascularization- in Early with high-risk features as predicted by a positive I, A biomarker with high-risk features as predicted by risk positive patients assay, ST segment changes or a high a score 58-61 according to assay, ST segment changes or a high risk score . biomarker the TIMI scale or equivalent according to the TIMI scale or equivalent 58-61. Routine invasive evaluation is not recommended in low risk IIb, B patients 58-61. 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 or silent ischemia. to have non-invasive However these patients are recommended assessment for inducible or silent32 ischemia.
32
31
8.2 8.2Routine early conservative management (selective invasive Routine early conservative management (selective invasive therapy) 63,64,65 therapy) 63,64,65
I, A I, A
TheThe use of aggressive anticoagulantantiplatelet agents has has use of aggressive anticoagulant and and antiplatelet agents alsoalso reduced incidence of adverse outcomes in patients reduced the the incidence of adverse outcomes in patients managed managed conservatively63,64,65. conservatively63,64,65. Selective Selectivecoronary coronary angiography/revascularization is indicated for those thosecannotcannot angiography/revascularization is indicated for who who be be stabilized medically in whom objective evidence of stabilized medically or or in whom objective evidence of significant ischemia is provoked in thein the sub acute phase. significant ischemia is provoked sub acute phase. A conservative strategy is recommended for women who are are A conservative strategy is recommended for women who stabilized and and remain biomarker negative 66. stabilized remain biomarker negative 66. An early invasive or conservative therapy is a reasonable option option An early invasive or conservative therapy is a reasonable for menmen who stabilized and remain biomarker negative 66. for who are are stabilized and remain biomarker negative 66. Patients with with UA/NSTEMI treated conservatively are at risk of Patients UA/NSTEMI treated conservatively are at risk of developing recurrent adverse cardiac events. Thus Thus these developing recurrent adverse cardiac events. these patients need to be evaluated patients need to be evaluated periodically for reversible periodically for reversible ischemia using non non invasive tests. If ischemia is present, they ischemia using invasive tests. If ischemia is present, they should be be considered for coronary angiography and should considered for coronary angiography and revascularization. revascularization.
IIa, A A IIa,
IIa, A A IIa,
Key messages Key messages Patients with with refractory angina and/ or hemodynamically unstable Patients refractory angina and/ or hemodynamically unstable should considered for for urgent coronary angiography should be be considered urgent coronary angiography and and revascularization I,C. I,C. revascularization Intermediate/high risk risk patients should considered for early early Intermediate/high patients should be be considered for invasive strategy (<72(<72 hours) admitted to a non-PCI centre, they they invasive strategy hours) I,A. If I,A. If admitted to a non-PCI centre, should be considered for transfer to a PCI centre I,B. (Flowchart 1, should be considered for transfer to a PCI centre I,B. (Flowchart 1, pg 3) 3) pg LowLow risk patients should be assessed non-invasively for ischemia I,C. risk patients should be assessed non-invasively for ischemia I,C. (Fig(Fig 1,5) 5) 1, pg pg 9 9 UA/NSTEMI IN SPECIAL GROUPS UA/NSTEMI IN SPECIAL GROUPS All patients should receive optimal medical therapy. (Table(Table4) pg 4) All patients should receive optimal medical therapy. 1, pg 1,
9.1 9.1UA/NSTEMI in the Elderly UA/NSTEMI in the Elderly Cardiovascular morbidity and mortality increases by 70% for every every 10 Cardiovascular morbidity and mortality increases by 70% for 10 year increase in age18,67-68. year increase in age18,67-68.
33
32
33
9.1.1 9.1.1 Clinical presentation: Clinical presentation:
AA high index of suspicion is necessary to make a diagnosis of high index of suspicion is necessary diagnosis of UA/NSTEMI in elderly patients. Atypical presentations occur more UA/NSTEMI in elderly patients. Atypical presentations more frequently. These include: frequently. These include: dyspnoea dyspnoea diaphoresis diaphoresis nausea and vomiting nausea and vomiting neurological symptoms such as acute confusional states and neurological symptoms such as acute states and syncope syncope ACS frequently develops as a secondary coronary event in the setting ACS frequently develops as a secondary coronary setting of another acute illness e.g. pneumonia. The elderly often are in heart of another acute illness e.g. pneumonia. The heart diagnostic. failure at the time of presentation 69.. The ECGs may be non diagnostic. failure at the time of presentation 69 The ECGs
9.1.2. Management 9.1.2. Management There is limited trial data to guide management in the elderly especially especially There is limited trial data to guide management in the setting of advanced age (more than 75 years) or significant cosignificant coin the setting of advanced age (more than morbidity (e.g. prior stroke, renal impairment). One should consider the consider the morbidity (e.g. prior stroke, renal impairment). biological age rather than the chronological age of the patient when when biological age rather than the chronological making management decisions. The elderly are a heterogenous group group making management decisions. The elderly and the risk benefit ratio of each intervention should be individualized. individualized. and the risk benefit ratio of each intervention Creatinine clearance should be calculated to enable appropriate drug drug Creatinine clearance should be calculated dosing. (Appendix VI,pg 56) dosing. (Appendix VI,pg 56)
I, I, A A
Both aspirin and clopidogrel (especially Both aspirin and clopidogrel (especially in those undergoing PCI) undergoing PCI) 70,71 confer greater absolute and relative benefits confer greater absolute and relative benefits in the elderly 70,71.. Prasugrel should be avoided in patients Prasugrel should be avoided in patients older than 75 years in years in view of the bleeding risk 31.. view of the bleeding risk 31 In aameta-analysis, both UFH and LMWH were equally effective in effective in In meta-analysis, both UFH and LMWH agents. the elderly 72. .However bleeding risk is higher with both agents. the elderly 72 However bleeding risk is Elderly patients have more bleeding complications with the use of use of Elderly patients have more bleeding complications GPIIb/IIIa inhibitors 73,74.. If required, the dose should be adjusted adjusted GPIIb/IIIa inhibitors 73,74 If required, the according to the renal function. according to the renal function. The elderly have greater in-hospital and long term benefits with benefits with The elderly have greater in-hospital of an an early invasive strategy 75-79.. In some trials, all the benefits of an an early invasive strategy 75-79 In some early invasive strategy were in the elderly rather than in younger patients 75. However there is an increased risk of major bleeding 80. 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, B B
I, I, A A I, I, B B
I, I, A A
CliniCal PraCtiCe Guidelines on manaGement of unstable anGina/non st elevationinvasivestrategy were ininthe elderly rather than in2011 early invasive strategy were in the elderly rather than in younger early invasive strategy were early myoCardial infarCtion (ua/nstemi) in younger the elderly rather than
patients 7575However there isisan increased risk of major bleeding 80. . patients 75.. . Howeverthere is an increased risk of major bleeding 80 patients However there an increased risk of major bleeding When selecting patients for an early invasive strategy, the risk When selecting patients for an early invasive strategy, the risk When selecting patients for an early invasive strategy, benefit ratio must be considered. For patients with multi vessel benefit ratio must be considered. For patients with multi vessel benefit ratio must be considered. For patients with multi disease and not suitable for CABG, partial revascularization of the disease and not suitable for CABG, partial revascularization of the disease and not suitable for CABG, partial revascularization culprit lesion may be a aconsideration. culprit lesion may be a consideration. culprit lesion may be consideration. Long term management post discharge should include Long term management post discharge should include Long term management post discharge should medications that have been proven beneficial in secondary medications that have been proven beneficial in secondary medications that have been proven beneficial in secondary prevention. prevention. prevention. 9.2 9.2 UA/NSTEMI in Women UA/NSTEMI in Women UA/NSTEMI in Women
Women develop CAD about a adecade later than men at aatime when Women developCAD about a decade later than men at a time when develop CAD about decade later than men at time they are older and have more co-morbidity such as obesity, diabetes, they are olderand have more co-morbidity such as obesity, diabetes, older and have more co-morbidity such as obesity, diabetes, hypertension and osteoarthritis 8181. However gender is not an hypertension and osteoarthritis 81. However gender is not an hypertension and osteoarthritis . However gender is not independent predictor ofof11year survival. independent predictor of 1 year survival. independent predictor year survival. 9.2.1 Clinical Presentation 9.2.1 Clinical Presentation Clinical Presentation Women presenting with ACS often have atypical symptoms such Women presenting with ACS often have atypical symptoms such Women presenting with ACS often have atypical symptoms as neck and shoulder ache and dyspnoea. Often, women have asneck and shoulder ache and dyspnoea. Often, women have neck and shoulder ache and dyspnoea. Often, women non specific ECG changes such as TTwave changes even in the nonspecific ECG changes such as T wave changes even in the specific ECG changes such as wave changes even absence ofofheart disease, thus making the diagnosis of CAD absence of heart disease, thus making the diagnosis of CAD absence heart disease, thus making the diagnosis of difficult. difficult. difficult. 9.2.2 9.2.2 9.2.2 Management Management Management
InIn general,there are no gender specific differences in the efficacy general, there are no gender specific differences in the efficacy general, there are no gender specific differences in the efficacy ofofthe commonly used drugs in ACS. The following are some the commonly used drugs in ACS. The following are some the commonly used drugs in ACS. The following are important differences: important differences: important differences:
I, B B I,
Prasugrel associated with more bleeding in individuals Prasugrel isisassociated with more bleeding in individuals who Prasugrel is associated with more bleeding in individuals who are less than 60kg weight . are less than 60kg ininweight 3131. are less than 60kg in weight 31. meta-analysis indicates lack of benefit of GPIIb/IIIa A A meta-analysis indicates aa lack of benefit of GPIIb/IIIa meta-analysis indicates a lack of benefit of GPIIb/IIIa inhibitors women The bleeding risk also higher. inhibitors inin women82.. The bleeding risk isis alsohigher. inhibitors in women 8282.The bleeding risk isalso higher. There conflicting data regarding the benefits of an There isisconflicting data regarding the benefits of an early There is conflicting data regarding the benefits of an early invasive strategy women with UA/NSTEMI 66,84-86 Until invasive strategy ininwomen with UA/NSTEMI 66,84-86. ..Until this invasive strategy in women with UA/NSTEMI 66,84-86 Until this issue isisresolved ininrandomized controlled trials, an invasive issue is resolved in randomized controlled trials, an invasive issue resolved randomized controlled trials, an invasive strategy isisbest reserved for women with ongoing ischemia and strategy is best reserved for women with ongoing ischemia and strategy best reserved for women with ongoing ischemia raised troponins. raised troponins. raised 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 Gault formula (Appendix VI, pg 56). Drug doses should be adjusted according to renal function.
I, B B I,
IIa, A A IIa,
9.3
I, B
9.3
CliniCal Chronic Kidney Disease (CKD) UA/NSTEMI in PraCtiCe Guidelines 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 Cr Cl 50 ml/min Cr Cl <<50 ml/min 36 Tirofiban IV infusion 0.4 mcg/kg/min IV infusion 0.05 mcg/kg/min if if Tirofiban IV infusion 0.4 mcg/kg/min IV infusion 0.05 mcg/kg/min for 30 mins Cr Cl <30 ml/min for 30 mins Cr Cl <30 ml/min * * Modifiedfrom 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 J Am CollCardiol 2007; 50:1-157. 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. The mortality following an ACS 94,95. The Diabetics have an 35 glucose level at admission has been shown to be aasignificant significant glucose level at admission has been shown to be
Fondaparinux Avoid if Cr Cl < 30 ml/min Avoid if Cr Cl <mcg/kg/min if Eptifibatide 180 mcg/kg IV Infusion 1.0 30 ml/min Eptifibatide 180 PraCtiCe Guidelines ml/min IV Infusion on mcg/kg/min if CliniCal mcg/kg Cr Cl < 50 1.0 Tirofiban IV infusion 0.4 mcg/kg/min Cr infusion ml/minst IV Cl < 50 0.05 manaGement of unstable anGina/non mcg/kg/min if Tirofiban IV infusion 0.4 mcg/kg/min IV infusionml/min for 30 mins infarCtion Cr Cl <30 0.05 mcg/kg/min if elevation myoCardial (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. * Am Coll Cardiol 2007; 50:1-157. J Modified from ACC/AHA 2007 Guidelines for the Management of Patients with UA/NSTEMI.
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. The Diabetics have an increased mortality shown an ACS 94,95. The glucose level at admission has been followingto be a significant glucose level yearadmission with abeen shown to equivalent to LV predictor of 1 at mortality has predictive value be a significant predictor of 1 year mortality with a predictive value equivalent to LV systolic dysfunction 96,97. 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 found and more effective in diabetics Prasugrel has been aspirinto be clopidogrel or prasugrel. 31. 31 Prasugrel has been found contemporary trial indicated only GP IIb/IIIa inhibitors a to be more effective in diabetics . a 98,99 GP IIb/IIIa inhibitors a contemporary trial indicated only a modest reduction in adverse events 98,99. . modest reduction in adverse events Early invasive approach diabetics are however at higher risk Early invasive approachthan non diabetics. diabetics are however at higher risk of contrast nephropathy of contrast nephropathy than non diabetics. There is still a lack of consensus on the optimal management of There is still during the acute event. Intensive insulin therapy to blood sugars a lack of consensus on the optimal management of blood sugars during the the acute setting has insulin therapy to achieve normoglycemia inacute event. Intensive not been shown to achieve normoglycemia in the acute setting has not been episodes reduce mortality and is associated with an increase in the shown to reduce mortality and is associated with an is to keep the episodes of hypoglycemia100. A general consensus increase in blood sugars of hypoglycemia100.in the acute setting and to keep blood optimal less than 8mmol/l A general consensus is then aim for sugars less than 8mmol/l in the control following discharge.acute setting and then aim for optimal 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 acute phase of of ischaemic is usually STEMI months. The risk of recurrence UA/NSTEMI events, 1 to 3 or death is risk of during this period. Following this, most patientsdeath is highest recurrence of ischaemic events, STEMI or assume highest during this period. Following this, most patients assume a clinical course similar to that of patients with chronic stable a clinical course similar to that of patients with chronic stable angina. angina. lifestyle modification measures and drug therapies have Several Several lifestyle modification measures and drug therapies have been shown to be effective 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 PraCtiCe Guidelines on CliniCal safe use. 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
CliniCal PraCtiCe Guidelines patients with -blockers should be continued indefinitely in on

reduced LV of unstable anGina/non st manaGementfunction, with or without symptoms of heart 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 7: Recommended dosages of ACE-I in UA/NSTEMI Table 7: Recommended dosages of ACE-I in UA/NSTEMI Table 7: Recommended dosages of ACE-I in UA/NSTEMI Type Initiation dose Target dose Type Initiation dose Target dose Type Initiation dose Target dose Captopril 6.25 mg bd-tds 25-50 mg tds Captopril 6.25 mg bd-tds 25-50 mg 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 mg od 20 mg bd Enalapril 2.5-5 mg od 20 mg 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 od 8-10 mg od Perindopril 2-2.5 mg od 8-10 mg od Perindopril 2-2.5 mg od 8-10 mg 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 Blockers (ARBs) (Table 8, pg 39) 10.1.5 Angiotensin-Receptor Blockers (ARBs) (Table 8, pg 39) 10.1.5 Angiotensin-Receptor Blockers (ARBs) (Table 8, pg 39) I, A ARBs should be substituted for patients with ACE-I I, A ARBs should be substituted for patients with ACE-I I, A ARBs should intolerance 125-127. be substituted for patients with ACE-I 125-127 I, A ARBs should intolerance 125-127. be substituted for patients with ACE-I intolerance 125-127. intolerance . Table 8: Recommended dosages of ARB in UA/NSTEMI Table 8: Recommended dosages of ARB in UA/NSTEMI Table 8: Recommended dosages of ARB in UA/NSTEMI Table 8: Recommended dosages of ARB in UA/NSTEMI Type Initiation dose Target dose Type Initiation dose Target dose Type Initiation dose Target dose Type Initiation dose Target dose Valsartan 40-80 mg od 160 mg od Valsartan 40-80 mg od 160 mg od Valsartan 40-80 mg od 160 mg od Valsartan 40-80 mg od 160 mg od 10.1.6 Aldosterone receptor antagonist 10.1.6 Aldosterone receptor antagonist 10.1.6 Aldosterone receptor antagonist 10.1.6 Aldosterone receptor antagonist Long-term aldosterone receptor blockade should be considered I, B Long-term aldosterone receptor blockade should betreated with Long-term who are in heart failure and already considered in patients aldosterone receptor blockade should be considered I, B I, B Long-term aldosterone receptor blockade should betreated with considered in patients -blockers.in heartagents include spironolactone with ACE-I and who are These failure and already in patients who are in heart failure and already treated and I, B in patients -blockers.in heartagents include spironolactone with who failure and already treated 128,129are ACE-I and -blockers. These agents include spironolactone and epleronone ACE-I and 128,129. These and 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 should be taken in patients with renal dysfunction and hyperkalaemia. taken in patients with renal dysfunction and Care should be Care should be taken in patients with renal dysfunction and hyperkalaemia. hyperkalaemia. 10.1.7 hyperkalaemia. Anti Anginal Therapy 10.1.7 Anti Anginal Therapy 10.1.7 Anti Anginal Therapy 10.1.7 Anti Anginal Therapy required for patients with successful Anti anginals are not I, C Anti anginals are not required for patients with successful revascularization and no required ischaemia. Anti anginals are not residual for patients with successful I, C I, C Anti anginals are not for patients with successful revascularization and no required ischaemia. I, C revascularization and no residual ischaemia. residual 10.2 Follow-up investigations (Fig 1,ischaemia. revascularization and no residual pg 5) 10.2 Follow-up investigations (Fig 1, pg 5) 5) 10.2 Follow-up investigations (Fig 1, pg UA/NSTEMI patients, the In the Follow-up investigations (Fig 1, pg 5) outpatient evaluation of low risk 10.2 following investigations maybe of low risk UA/NSTEMI patients, the In the outpatient evaluation of low risk UA/NSTEMI patients, the In the outpatient evaluation considered: 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 Echocardiogram test Echocardiogram to assess LV function to assess LV function Stress echocardiogram treadmill or pharmacological stress Echocardiogram test Treadmill stress test Treadmill stress to assess LV function Nuclear perfusion study treadmill or pharmacological stress Treadmill stress test Stress echocardiogram Stress echocardiogram treadmill or pharmacological stress MRI stress MRI for ischaemia and perfusion MRI for viability Stress echocardiogram treadmill or pharmacological stress Nuclear perfusion study Nuclear perfusion study 40 Nuclear perfusion study MRI stress MRI for ischaemia and perfusion MRI for viability MRI stress MRI for ischaemia and perfusion MRI for viability MRI stress MRI for ischaemia and perfusion MRI for viability 40
39
40 40
Low risk patients with significant demonstrable ischaemia and all Low risk patients with significant demonstrable ischaemia and all Low risk patients with significant be considered for revascularization. intermediate/high risk patients should demonstrable ischaemia and all intermediate/high risk patients should be considered for revascularization. intermediate/high risk patients should be considered for revascularization. Key messages Key messages Key messages Patients should be on optimal medical therapy at discharge. This Patients should be on optimal medical therapy at discharge. This Patients should , clopidogrel (for at least a monthdischarge. This be on optimal medical therapy at includes ASA I,A, clopidogrel (for at least a month and ideally for includes ASA I,A,I,B includesa year) I,B, -blockers I,B at CCBsa month and or ARBfor ASA I,A clopidogrel (for + least I,C, ACE-I I,A ideally for and ideally I,B at least at least a year) I,B, -blockers I,B + CCBs I,C, ACE-I I,A or ARB I,B at least a year) , -blockers I,B + CCBs I,C, ACE-I I,A or ARB I,B I,A and statins I,A. (Table 1, pg 4) and statins I,A. (Table 1, pg 4) and statins . (Table 1, pg 4) These drugs should be uptitrated during outpatient visits to the These drugs should be uptitrated during outpatient visits to the These drugs should be doses I,C. during outpatient visits to the uptitrated recommended tolerated doses I,C. recommended tolerated recommended tolerated doses I,C. Low risk patients should be assessed non-invasively for Low risk patients should be assessed non-invasively for Low risk I,C. (Fig 1, pg 5) patients should be assessed non-invasively for ischaemia I,C ischaemia I,C. (Fig 1, pg 5) ischaemia . (Fig 1, pg 5) 11. Cardiac Rehabilitation/Secondary prevention 11. Cardiac Rehabilitation/Secondary prevention Cardiac rehabilitation is aimed at improving the physical and psychological Cardiac rehabilitation is aimed has been shown to reduce mortality by well being of the patient. It at improving the physical and psychological well being of 20%-25% 130-132.has been shown to reduce mortality by approximately the patient. It There was also a trend towards reduction 130-132 There follow-up of 12 months 133reduction approximately 20%-25%over a .median was also a trend towards . in non-fatal recurrent MI 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 factors such as high blood pressure, Helping the patient modify risk Helping the patient modify risk factors such inactivity, obesity and smoking, high blood cholesterol, physical as high blood pressure, smoking, high blood cholesterol, physical inactivity, obesity and diabetes diabetes vocational guidance to enable the patient to return to work Providing Providing vocational guidance to enable the patient to return to work Supplying information on physical limitations Supplying information on physical limitations Supplying information on physical limitations Educating and ensuring compliance to medications Educating and ensuring compliance to medications Educatingemotional support Providing and ensuring compliance to medications Providing emotional support Providing emotional support Cardiac rehabilitation/secondary prevention programs are generally Cardiac rehabilitation/secondary prevention programs are generally Cardiac rehabilitation/secondary prevention programs are generally divided into 3 main phases: divided into 3 main phases: divided into 3 main phases: Phase 1: Inpatient CR (also known as Phase 1 CR): a program that Phase 1: Inpatient CR (also known as Phase 1 CR): a program that Phase 1: Inpatient CR (also known as Phase to CR): a program that delivers preventive and rehabilitative services to hospitalized patients delivers preventive and rehabilitative services 1 hospitalized patients following ACS delivers preventive and rehabilitative services to hospitalized patients following ACS following ACS Phase 2: Early outpatient CR (also known as Phase 2 CR): generally Phase 2: Early outpatient CR (also known as Phase 2 CR): generally within 2: first to 6 months but continuing up to 1 year Phasethe Early3outpatient CR (also known as Phase 2 CR): generally within the first 3 to 6 months but continuing up to 1 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) or Phase Phase 3: Long-term outpatient CR (also known as Phase 3 2011
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 Elevations of cardiac troponin the absence of Appendix II:II: Elevationsof cardiac troponin inin the absence of overt ischaemic heart disease* overt ischaemicheart disease* Damage related secondary myocardial ischaemia (MI type Damage related to to secondarymyocardial ischaemia (MI type 2) 2)
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 heart failure without significant concomitant coronary artery disease (CAD) disease (CAD) cardiomyopathy Hypertrophic Hypertrophicvasculitis, e.g. systemic lupus erythematosus, Kawasaki syndrome Coronary cardiomyopathy Coronary vasculitis, e.g. systemic withouterythematosus, Kawasaki syndrome Coronary endothelial dysfunction lupus significant CAD, 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 Cardiac contusion with surgery 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 groupsurface body Indeterminant or multifactorial
Indeterminant or multifactorial group Apical ballooning syndrome

Severe pulmonary embolism or pulmonary hypertension
Apical ballooning syndrome Peripartum cardiomyopathy Severe pulmonary embolism or pulmonary hypertension Renal failure Severe cardiomyopathy Peripartumacute neurological diseases, e.g. stroke, trauma 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 Extreme exertion failure Frequent defibrillator shocks Sepsis Acute respiratory failure *Thygesen K, Mair J,Katus H et Frequent defibrillator shocksal for Study Group on Biomarkers in Cardiology of the ESC
*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 III: Likelihood That Signs and Symptoms Represent an ACS Appendix III: Likelihood That Symptoms Represent an ACS secondary to CAD secondary CAD Greater Likelihood Greater Likelihood History History Chest or left arm pain or discomfort as Chest or left arm pain or discomfort chief symptom reproducing prior chief symptom reproducing prior documented angina documented angina Known history of CAD, including MI Known history of CAD, including New chest or left arm pain or discomfort New chest or left arm pain or as chief symptom as chief symptom Age greater than 70 years Age greater than 70 years Male sex Male sex Diabetes mellitus Diabetes mellitus Examination Examination Transient MR murmur, hypotension, Transient MR murmur, hypotension, diaphoresis, pulmonary edema, or rales diaphoresis, pulmonary edema, Extracardiac vascular disease Extracardiac vascular disease ECG ECG New, or presumably new, transient STNew, or presumably new, transient T-wave attening or inversion T-wave attening or inversion segment deviation (1 mm or greater) or T- less than 1 mm in leads with segment deviation (1 mm or greater) less than 1 mm in leads with wave inversion in multiple pre-cordial wave inversion in multiple pre-cordial dominant R waves dominant R waves leads leads Normal ECG Normal ECG Cardiac Biomarkers Cardiac Biomarkers Elevated cardiac TnI, TnT, or CK-MB Elevated cardiac TnI, TnT, or markers markers Normal Normal Chest discomfort reproduced Chest discomfort reproduced by palpation by palpation Chest pains in the absence of Chest pains in the absence of any of the greater likelihood any of the greater likelihood characteristics characteristics Recent cocaine use Recent cocaine use Lower Likelihood Lower Likelihood
Modified from Braunwald E, et al. Unstable Angina: Diagnosis and Management. 1994;3-1Modified from Braunwald E, et al. Unstable Diagnosis and Management. 1994;3-1AHCPR Publication No 94-0602:1-154. AHCPR Publication No 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 risk or older At least 3 65 y factors for CAD ( family history of premature CAD, At least 3 risk factors for CAD family history diabetes) hypertension,elevated cholesterols,(active smoker,of premature CAD, 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 deviation (>0.5mm) on ST-segmentaspirin in prior 7 days ECG ST-segment deviation (>0.5mm) h At least 2 anginal episodes in prior 24 on 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 Low Risk: < 2 point Moderate Risk :3-4 points HighModerate Risk: 3-4 points Risk : >5 points High Risk : >5 points
Adapted from : Adapted from : Cohen M, Bernink PJ, et al. The TIMI risk score for unstable Antman EM,
Antman elevation MI: a Bernink prognostication TIMI risk score for unstable angina/non-ST EM, Cohen M,method forPJ, et al. The and therapeutic decision angina/non-ST elevation MI: . making. JAMA 2000; 284 : 83542 a method for prognostication and therapeutic decision making. Morrow DA, : 83542 Sabatine MS,JAMA 2000; 284Giugliano . RP, et al. Implications of upstream Sabatine MS, Morrow and coronary artery al. Implications of upstream glycoprotein IIb/IIIa inhibition DA, Giugliano RP, et stenting in the invasive glycoprotein IIb/IIIa angina/non ST elevation myocardial infarction. A management of unstable inhibition and coronary artery stenting in the invasive management of unstable angina/non Infarction (TIMI) IIIB trial infarction. A comparison of the Thrombolysis in Myocardial ST elevation myocardial and the Treat comparison of the Thrombolysis in Myocardial Infarction (TIMI) Invasive or the angina with Aggrastat and determine Cost of Therapy with IIIB trial and Treat angina with Aggrastat and trial. Circulation 2004; 109 : with Invasive or Conservative Strategy (TACTICS)-TIMI 18determine Cost of Therapy 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 NOMOGRAM APPENDIX GRACE PREDICTION SCORE CARD AND 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 VI: VI: Calculation Of Creatinine Clearance APPENDIX Calculation Of Creatinine Clearance APPENDIX VI: Calculation Of Creatinine Clearance APPENDIX VI: Calculation Of Creatinine Clearance Estimated GFR (ml/min) = (140-age) x weight Estimated GFR (ml/min) = (140-age) x weight or or (140-age) 1.2 1.2 (140-age) Estimated Estimated GFR (ml/min) = (140-age) x weight1.2 (140-age) (140-age) GFR (ml/min) = (140-age) x weight or or 1.2 (0.814 x SCr [mol/L ]) ]) (0.814 x SCr [mol/L SCr [mol/L ] SCr [mol/L ] ]) S] (0.814 x S(0.814 x SCr [mol/LSCr [mol/L Cr [mol/L ] Cr [mol/L ]) SCr : SCr : serum creatinine serum creatinine SCr : serum creatinine creatinine SCr : serum For women multiply by 0.850.85 For women multiply by For women multiply by 0.85 by 0.85 For women multiply Severity Of CKD* Severity Of CKD* Severity Of CKD* Of CKD* Severity SEVERITY OF CKD SEVERITY OF CKD CREATININE CLEARANCE CREATININE CLEARANCE SEVERITY OF CKD OF CKD SEVERITY CREATININE CLEARANCE CREATININE CLEARANCE Normal to mild mild Normal to >60 >60 ml/min ml/min Normal toNormal to mild mild >60 ml/min >60 ml/min Moderate Moderate 30-59 ml/min 30-59 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 Kidney Foundation. K/DOQI clinical practice guidelines for chronic * National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney National Kidney Foundation. K/DOQI and disease: evaluation, classification, stratification. Am Jchronicfor J * kidney disease: Foundation. K/DOQI clinical and clinicalstratification. Am Kidney chronic National *Kidney evaluation, classification, practice guidelines guidelines Kidney practice for Dis.2002;kidney disease: evaluation, classification, and stratification. Am J Kidney 39 (suppl 1): S1S226 kidneyDis.2002; 39evaluation,S1S226 disease: (suppl 1): classification, and stratification. Am J Kidney Dis.2002; 39 (suppl 1): S1S226 S1S226 Dis.2002; 39 (suppl 1):
APPENDIX VII: Prevention of Contrast Induced Nephropathy APPENDIX VII: Prevention of Contrast Induced Nephropathy APPENDIX VII: Prevention of Contrast Induced Nephropathy APPENDIX VII: Prevention of Contrast Induced Nephropathy ACC/ESC ACC/ESC Classification Classification ACC/ESCACC/ESC Classification Classification Contrast Agent Contrast Agent - Isomolar agent Agent - Isomolar agent I, A I, A Contrast Agent Contrast - Low Low Isomolar agents - osmolar osmolar agent IIa, B B I, A - Isomolar -agent agents I, A IIa, - use minimalagents - Low - use Lowvolume agents osmolar osmolar - minimal volume IIa, I, C I, C B B IIa, - use minimal volume volume - use minimal I, C I, C Avoid nephrotoxic agents eg eg Avoid nephrotoxic agents I, C I, C NSAIDS,metforminagents egagents eg NSAIDS,metformin Avoid nephrotoxic Avoid nephrotoxic I, C I, C NSAIDS,metformin NSAIDS,metformin Saline Infusion Saline Infusion I, C I, C Saline Infusion Infusion Saline I, C I, C Sodium Bicarbonate Sodium Bicarbonate IIa, B B IIa, Sodium Bicarbonate Sodium Bicarbonate IIa, B IIa, B Acetylcysteine Acetylcysteine IIb, B B IIb, 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 / FLOW RATE CONCENTRATION DOSE / FLOW RATE Rate 1.0-1.5 ml/kg/hr for Rate ofof 1.0-1.5 ml/kg/hrfor 3h-12h before and 6h-24h 3h-12h before and 6h-24h after the procedure ensuring after the procedure ensuring a a urine flow rate of 150 urine flow rate of 150 ml/hour ml/hour Reduce rate to 0.5 ml/kg/hr Reduce rate to 0.5 ml/kg/hr ifif 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 infusionafter the procedure of 1 ml/kg/hr for 6 hours hours after the procedure
Sodium Chloride* 0.9% solution Sodium Chloride* 0.9% 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 mlmEq/l of of 1000 1000 mEq/l of sodium bicarbonate sodium bicarbonate + 850 ml of 5% + 850 ml of 5% Dextrose) Dextrose)
1200 mg twice daily, one day 1200 mgand one day one day before twice daily, after the before and one day after the contrast contrast
2006; 6929. 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 C, Colombo A, Violante A et al. Standard vs double dose of : 206-211. ** Briguori contrast agent associated nephrotoxicity. Eur Heart J 2004; 25 N-acetylcysteine to prevent contrast agent associated nephrotoxicity. Eur Heart J 2004; 25 : 206-211. *** Tepel M, Van der Giet M, Schwarzfeld C et al. Prevention of radiographic-contrastTepel M, Van der Giet in Schwarzfeld by al. Prevention of radiographic-contrast*** agent-induced reductions M, renal functionC etacetylcysteine. N Engl J Med. 2000; 343: 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 PA, Bertrand ME, with JA, Stacul contrast media. J Am Coll Cardiol. of * McCulloughiodixanol comparedBrinkerlow-osmolar F. A meta-analysis of the renal safety 48:
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ACKNOWLEDGMENTS ACKNOWLEDGMENTS The committee of this guideline would like to express their gratitude and The committee the this guidelinetheir contribution: appreciation to of following for would like to express their gratitude and appreciation to the following for their contribution: Technical Advisory Committee, Clinical Practice Guidelines, Ministry of Technical Advisory Committee, Clinical Practice Guidelines, Ministry of Health for their valuable input and feedback Healthof external reviewers who reviewed the draft Panel for their valuable input and feedback Panel of external reviewers who reviewed the draft Secretarial assistance from 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) Sdn Bhd. Sanofi-Aventis made possible Sanofi-Aventis guideline. Bhd. content of this (M) Sdn content of this guideline.
by an unrestricted educational grant from by an unrestricted educational grant from The funding body 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 Rajadurai Rajadurai Dr. Jeyamalar

mad Nizar Dr. Ahmad Nizar

uar Rapaee Dr. Anuar Rapaee Chandran Chandran Dr. Aris

ar IsmailOmar Ismail Dr.

h Maskon Dr. Oteh Maskon

e Raman Dr. Sree Raman

Kui Dr. Sim Kui Hian Hian

n Azman Dr. Wan Azman

bayaah Zambahari Zambahari Dr. Robayaah

Dr. Chan Hiang Chuan Dr. Chan Hiang Chuan

Dr. Jeyaindran Sinnadurai Dr. Jeyaindran Sinnadurai

Dr. Lee Chuey Yan Dr. Lee Chuey Yan

Dr. Lee Fatt Soon Fatt Soon Dr. Lee

Dr. Kim Tan Kim Tan Dr.

Dr. V Paranthaman Dr. V Paranthaman

Dr. Santha Kumari Kumari Dr. Santha

Dr. Tee Lian Kim Lian Kim Dr. Tee

Dr. Wong Kai Wong Kai Fatt Dr. Fatt

Dr. Zurkarnai Yusof Dr. 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

10 30-60mg, 2 3 times 20 mg daily, ( max 120 mg ) daily

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

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

CliniCal Chronic Kidney Disease (CKD) UA/NSTEMI in PraCtiCe Guidelines on

UA/NSTEMI in Diabetes UA/NSTEMI in Diabetes

10.1.1 Antiplatelet agents

ASA should be prescribed at 75-150 mg daily unless

Patients given sublingual nitrates should be instructed in its

Sodium Sodium Bicarbonate Bicarbonate