RMGH NEWSLETTER

{mosimage}Guidelines for the Management of Post-MI Patients in the Outpatient Settings
Ramaz Mitaishvili, MD
Gina Gagua, LAc, PhD

Introduction
Compelling clinical trial evidence exists that antiplatelet, ß-blocker, angiotensin-converting enzyme (ACE) inhibitor, and lipid-lowering therapies reduce the risk of recurrent cardiovascular events, hospitalization, and heart failure and substantially improve survival in Post MI patients. Despite this evidence as well as clinical guidelines recommending these cardiovascular protective treatments in Post MI patients, a number of studies have documented low treatment rates in this patient population. The conventional approach to the initiation of lipid-lowering therapy was to not start therapy in the hospital for patients with acute MI; instead, the many practitioners recommended waiting a period of time until the patient was metabolically stable as an outpatient. 

 {mospagebreak}

Potential Organizational Barriers to Implementation
Potential barriers to the implementation of the guideline would be as follows:
     Lack of resources and facilities.
     Lack of access to diagnostic equipment including electrocardiogram machine within some outpatient’s clinics.
     Lack of specialist-generalist communication; passing on of responsibility.
     Increased prescribing costs. Inadequate prescription-medication benefits, restrictive formularies.
     Focus of physicians on acute problems.
     Time constraints and lack of incentives, including lack of reimbursement.
     Lack of physician training, including inadequate knowledge of benefits and lack of prescription experience.
     Guidelines that call for delaying.

Cardiovascular Risk Following MI
The cardiovascular risk after acute MI remains substantial. Patients with a prior history of MI are five to seven times more likely to sustain a cardiovascular event than are individuals without clinically evident atherosclerotic vascular disease. These post-infarction patients remain at risk for recurrent events even if they are entirely asymptomatic, have no demonstrated ischemia on stress testing, and have undergone complete revascularization. Patients after acute MI thus constitute a very high-risk group for recurrent cardiovascular events, hospitalizations, heart failure, and cardiovascular mortality. One of the major cause of  Sudden Cardiac Death are SCD to tachyarrhythmic events after a recent myocardial infarction (MI). Another cause of recurrent events is patients non-compliance due to post-MI depression, and other disorders (primary or secondary).

Criteria for Specialist Referral
Outpatient practitioner must be ready for specialist referral and develop individual strategy for each post-MI patient.  

1. Patients who have had a recent onset chest pain in the last 2 – 4 weeks should be referred to the Hospital.
2. Patients who have had previous assessment of chest pain in either the Cardiology clinic, A & E department or as an inpatient or outpatient, should be referred to the Cardiology Outpatient clinic in the normal way.
3. Patients suspected of having acute and severe pain in the background of stable angina should be referred to the A & E department as they could be
suffering from MI/unstable angina.
4. Except under exceptional circumstances, women under 40 and men under 30 should not be referred to the Hospital, because the probability of coronary heart disease in these groups is extremely low.
5. Patients with abnormal ECG’s are at greatest risk and should be considered for specialist referral.
6. Patients with chest pain and murmurs suggesting aortic stenosis should be considered for specialist referral.
7. Patients where clinical condition gives rise for concern, e.g. failure to respond to management/ treatment outlined in this guideline, pain at rest or at night, concurrent illnesses, particularly diabetes, should be considered for specialist referral.
8. Patient with signs and symptoms of post-MI Depression should be considered for specialist referral.

Indications for ICD therapy from the ACC/AHA Task Force on Practice Guidelines and endorsed by the North American Society for Pacing and Electrophysiology
    Cardiac arrest due to VF or VT not due to transient or reversible causes
    Spontaneous, sustained VT with structural heart disease
    Syncope with inducible, sustained, hemodynamically significant VT of VF, when drug therapy is not effective, tolerated, or preferred
    Nonsustained VT with coronary artery disease, prior MI, LV dysfunction, and inducible VF or sustained inducible VT not suppressible with a class I antiarrhythmic
    Spontaneous, sustained VT without structural heart disease, not amenable to other treatments
Treatment and Follow-up of the Post-MI patients

The Aims of the Outpatient practitioner
     To achieve and maintain patients’ BP at or less than 140/85 mmHg
     To achieve and maintain optimum control of blood pressure and glucose for diabetic patients
     To achieve and maintain patients’ total cholesterol level at or less than 100 mg/dL
     To achieve and maintain 100% of patients not smoking
     To advise on lifestyle modification, eg. Diet, management of obesity, alcohol consumption, exercise, and community physical activity programs, reinforced with appropriate literature
     To make referrals to specialist services where appropriate, eg. Dietitian, smoking
       cessation clinics
     To check compliance and patients’ understanding of current pharmacological
      intervention (see recommendations below)
     To check and discuss general health issues with patients

{mospagebreak}

Pharmacological Intervention
Today, post-MI patients are typically treated with thrombolytic therapy and revascularization procedures. Recovery is usually followed by cardiac rehabilitation, counseling on diet and lifestyle changes, and pharmacologic therapy, including aspirin, statins, blockers, angiotensin-converting enzyme (ACE) inhibitors and, in some cases, antiarrhythmic agents. Current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines recommend class 1 indications for aspirin therapy in all post-MI patients; statins in all patients with low-density lipoprotein cholesterol greater than 100 mg/dL; ßblocker therapy in all but either the lowest-risk patients or those with a clear contraindication; and ACE inhibitors in patients with prior MI and either ejection fraction (EF) less than 40% or congestive heart failure.

     Aspirin should be given routinely to and continued for life in patients A with CHD – a dose of 75-150 mg aspirin per day is recommended in post MI patients
     Clopidogrel (75 mg/day) is an effective alternative in patients A with contraindications to aspirin, or who are intolerant of aspirin.
     Caution should be exercised in the use of Clopidogrel, which can A cause GI upset in some patients.
     β-blocker therapy should be given to patients following myocardial infarction unless there are contraindications
     Long term ACE inhibitor therapy should be given to patients A following MI with or without left ventricular dysfunction, unless there are contraindications
     In post MI patients with left ventricular dysfunction, ACE inhibitor A therapy should be considered within 48 hours of the onset of symptoms – refer to guidelines for the management of heart failure
     Caution should be exercised in the use of ACE inhibitors in patients  who are hypotensive, who have moderate renal failure, or who are known to have renal artery stenosis.
     The initiation of Statin therapy should be considered in accordance of guidelines.

Benefits of Cardiovascular Protective Medications
As stated above, compelling evidence exists that antiplatelet therapy, ßblockers, ACE inhibitors, and lipidlowering therapy each reduce the risk of recurrent cardiovascular events, hospitalizations, heart failure, and mortality in patients following MI.
Each of these therapies individually has been demonstrated to have early as well as long-term benefits in patients presenting with MI.

Lipidlowering Medications Side Effect
We received tenth of adverse reports of patients receiving Lipidlowering medications. Statins can cause chronic aches and pains, liver inflammation, myopathy, numbness, weakness, confusion, fatigue, statin amnesia and other forms of memory dysfunction, hostility, aggression and profound depression, loss of libido and impotence, shortness of breath and even heart failure.
This chapter describes possible adverse of statins. Reports about adverse effects of statins are increasing dramatically, but they still vast minority. More reports have praised statins. We don’t have to speculate by reporting about negative or positive sides of  cholesterol lowering medications.  Another medications described above also characterized by some adverse effects, but they are minor compare to advantages. With lipidlowering drugs, each case must be evaluated individually, because cholesterol lowering medications can be replaced by some supplements. We strongly recommend to all outpatient physicians do not ignore any negative reports from post-MI patients about prescribed medications, because physicians have such a difficult time believing that their physical problems might be an adverse effect of those drugs. There will be no “conflict of interest” with guidelines, because we all have only interest- to help patients fight them condition. In addition be aware, that almost all lipidlowering medications are statins (different countries have different names for their statin drugs and many statins will become combined with other chemicals in the near future and assume even different names for patent protection and greater marketability), so replacing one medication by another can only aggravate the condition.
{mospagebreak}
 Conclusions
Despite compelling scientific evidence of the benefits of antiplatelet, ß-blocker, ACE inhibitor, and lipidlowering therapy, a substantial proportion of patients after acute MI are not on treatment with these evidence-based, guideline-recommended therapies. It has been clearly documented that not enough has been done to change this situation. Over half of the patients discharged after MI and lacking relevant contraindications or intolerance were not treated with all four of the key classes of medications. Under conventional management, less than 20% of patients discharged without one or more of the cardiovascular protective medications will be started on these drugs on an outpatient basis. The evidence from recent trials and clinical studies provides a compelling argument for prescribing a combination of cardiovascular protective medications in the hospital as part of a systematic approach to prevent remodeling and address the underlying atherosclerotic vascular disease process. Outpatient-based systems to ensure initiation of cardiovascular protective therapies have been demonstrated to improve treatment rates, long-term patient compliance, and clinical outcomes in patients with acute MI. Widespread application of outpatient-based cardiovascular protective treatment–initiation programs for acute MI could dramatically increase treatment rates with these proven, cost-effective therapies and thus substantially reduce the risk of recurrent cardiovascular events, heart failure, and hospitalizations in the large number of patients hospitalized with acute MI and save  many additional lives every year.

Main Points
    Following acute myocardial infarction (MI), patients face a high risk of recurrent cardiovascular events, hospitalizations, heart failure, and mortality.
    Antiplatelet therapy, ß-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins all reduce cardiovascular risks following acute MI, and their effects are additive.
    In-hospital initiation of aspirin, ß-blocker, ACE inhibitor, and lipid-lowering therapy has been shown to improve treatment rates, long-term patient compliance, and clinical outcomes in patients with acute MI and is now recommended as the standard of care in patients with coronary heart disease.
    Despite these findings and national guidelines, a substantial proportion of post-MI patients is not receiving these medications.
    Reasons for the under-use of these medications include the reluctance of physicians to prescribe ß-blockers to post-MI patients with left ventricular dysfunction and/or symptoms of heart failure; however, recent studies suggest that the ß-blocker carvedilol is safe and effective in these patients.
    Widespread implementation of hospital-based cardiovascular protective treatment–initiation programs for acute MI could dramatically increase treatment rates with these therapies and thus substantially reduce the risk of recurrent cardiovascular events, heart failure, and hospitalizations in the large number of patients admitted for acute MI every year.
{mospagebreak}

References and Recommended Reading
1.    A comparison of anti-arrhythmic drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular tachyarrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators [no authors listed]. N Engl J Med 1997, 337:1576-1583.
2.    Adams JE, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury: is MB creatine kinase the choice for the 1990s? Circulation 1993;88:750–63.
3.    Adult Treatment Panel II. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015–3023.
4.    Adult Treatment Panel III. Executive summary of The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486–2497.
5.    American Heart Association. Heart Disease and Stroke Statistics—2003 Update. Dallas, TX: American Heart Association, 2002.
6.    Anderson HV, Cannon CP, Stone PH, et al. One-year results of the Thrombolysis In Myocardial Infarction (TIMI) IIIB clinical trial: a randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol 1995;26:1643–50.
7.    Aronow HD, Topol EJ, Roe MT, et al. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study. Lancet. 2001;357:1063–1068.
8.    Bigger J, et al.: The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. Circulation 1984, 69:250-258.
9.    Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2002;106:1893–1900.
10.    Braunwald E, Mark DB, Jones RH, et al. Unstable angina: diagnosis and management. Rockville, MD: Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, US Public Health Service, US Department of Health and Human Services; 1994:1; AHCPR Publication No 94-0602.
11.    Burkart F, et al.: Effect of antiarrhythmia therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 1990, 16:1711-1718.
12.    Butler J, Arbogast PG, BeLue R, et al. Outpatient adherence to beta-blocker therapy after acute myocardial infarction. J Am Coll Cardiol. 2002;40:1589–1595.
13.    Buxton A: A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999, 341:1882-1890.
14.    Cairns J, et al.: Randomized trail of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarizations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997, 349:675-682.
15.    Cannon CP, McCabe CH, Bentley J, et al. Early statin therapy is associated with markedly lower mortality in patients with acute coronary syndromes: observations from OPUS-TIMI-16. J Am Coll Cardiol. 2001;35:334A.
16.    Connolly S, et al.: Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000, 101:1297-1302.
17.    Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357: 1385–1390.
18.    Debusk RF, Miller NH, Superko HR, et al. A case-management system for coronary risk factor modification after acute myocardial infarction. Ann Intern Med. 1994;120: 721–729.
19.    Dorian P, et al.: A randomized clinical trial of a standardized protocol for the prevention of inappropriate therapy in a dual chamber implantable cardioverter defibrillator [abstract]. Circulation 1999, 100:I-786.
20.    Echt D, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991, 324:781-788.
21.    Ellerbeck EF, Jencks SF, Radford MJ, et al, for the Cooperative Cardiovascular Project. Quality of care for Medicare patients with acute myocardial infarction: a four-state pilot study. JAMA. 1995;273:1509–1514.
22.    EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries; principal results from EUROASPIRE II Euro Heart Survey Program. Eur Heart J. 2001;22:554–572.
23.    Fonarow GC. Statin therapy after acute myocardial infarction: are we adequately treating high risk patients? Curr Athero Report. 2002;4:99–106.
24.    Fonarow GC, Ballantyne CM. In-hospital initiation of lipid lowering therapy for patients with coronary heart disease: the time is now. Circulation. 2001;103:2768–2770.
25.    Fonarow GC, French WJ, Parsons LS, et al, for the National Registry of Myocardial Infarction Participants. Use of lipid-lowering medications at discharge in patients with acute myocardial infarction: data from the National Registry of Myocardial Infarction 3. Circulation. 2001;103:38–44.
26.    Fonarow GC, Gawlinski A. Rationale and design of the Cardiac Hospitalization Atherosclerosis Management Program at the University of California Los Angeles. Am J Cardiol. 2000;85:10A–17A.
27.    Fonarow GC, Gawlinski A, Moughrabi S, et al. Improved treatment of cardiovascular disease by implementation of a cardiac hospitalization atherosclerosis management program: CHAMP. Am J Cardiol. 2001;87:819–822.
28.    Fonarow GC, Gawlinski A, Watson KA, Moughrabi S. Sustained Improvement in the treatment of Cardiovascular Hospitalization Atherosclerosis Management Program: CHAMP. Circulation. 2001;104:II-711.
29.    Gold M, et al.: Advanced rhythm discrimination for implantable cardioverter defibrillators using electrogram vector timing and correlation . J Cardiovasc Electrophysiol 2002, 13:1092-1097.
30.    Gregoratos G, et al.: ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 2002, 106:2145-2161.
31.    Guidant Corporation: ICD Therapy and Sudden Cardiac Death Prevention: A Decade of Clinical Evidence. A Background Report Prepared for the Medicare Coverage Advisory Committee; 2003.
32.    Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebocontrolled trial. Lancet. 2002;360:7–22.
33.    Higgins S, et al.: One VF induction is adequate for ICD implant: a subanalysis from the Low Energy Safety Study (LESS) [abstract]. PACE 2002, 22:549.
34.    Holdright D, Patel D, Cunningham D, et al. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994;24:39–45.
35.    Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288:462–467.
36.    Julian D, et al.: Randomized trial of the effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarction Amiodarone Trial Investigators. Lancet 1997, 349:667-674.
37.    Khalil ME, Basher AW, Brown EJ Jr, Alhaddad IA. A remarkable medical story: benefits of angiotensin-converting enzyme inhibitors in cardiac patients. J Am Coll Cardiol. 2001;37:1757–1764.
38.    Krum H, Roecker EB, Mohacsi P, et al. Effects of initiating carvedilol in patients with severe chronic heart failure: results from the COPERNICUS Study. JAMA. 2003;289:712–718.
39.    Krumholz HM, Radford MJ, Wang Y, et al. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project. JAMA. 1998;280:623–629.
40.    Kuck K: Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study of Hamburg (CASH). Circulation 2000, 102:748-754.
41.    Kupersmith J, et al.: Cost- effectiveness analysis in heart disease. Part III: ischemia, congestive heart failure and arrhythmias. Prog Cardiovasc Dis 1995, 37:307-346.
42.    LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282:2340–2346.
43.    Latini R, Tognoni G, Maggioni AP, et al. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group. J Am Coll Cardiol. 2000;35:1801–1807.
44.    Leclercq C: Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol 2002, 39:194-201.
45.    McCarthy M. US heart-guidelines program makes a promising start. Lancet. 2001;358:1618.
46.    35. Mehta RH, Montoye CK, Gallogly M, et al. Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative. JAMA. 2002;287:1269–1276.
47.    Moss A, et al.: Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996, 335:1993-1940.
48.    Moss A, et al.: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. Multicenter Automatic Defibrillator Implantation Trial II Investigators. N Engl J Med 2002, 346:877-883.
49.    Mushlin A, et al.: The cost effectiveness of automatic implantable cardiac defibrillators: results from MADIT. Circulation 1997, 97:2129-2135.
50.    Naccarelli G, et al.: A decade of clinical trial developments in postmyocardial infarction, congestive heart failure, and sustained ventricular tachyarrhythmia patients: from CASR to AVID and beyond. J Cardiovasc Electrophysiol 1998, 9:864-891.
51.    Neri SG, Gensini GF, Poggesi L, et al. Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina [erratum appears in Lancet 1990;335:868]. Lancet 1990;335: 615–8.
52.    Olatidoye AG, Wu AH, Feng YJ, Waters D. Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies. Am J Cardiol 1998;81:1405–10.
53.    Pacifico A: Implantable Defibrillator Therapy: A Clinical Guide. Boston: Kluwer Academic Publishers; 2002.
54.    Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–1658.
55.    Pearson RR, Horne BD, Maycock CA, et al. An institutional discharge medication program reduces future cardiovascular readmissions and mortality: an analysis of 43,841 patients with coronary artery disease. J Am Coll Cardiol. 2002;39:452A.
56.    Pearson TA, Laurora I, Chu H, et al. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000; 160:459–467.
57.    Pratt C: Can antiarrhythmic drugs survive survival trials? Am J Cardiol 1998, 81:24D-34D.
58.    Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol. 2000;36:2056–2063.
59.    Ruskin J, et al.: Implantable cardioverter defibrillator utilization based on discharge diagnoses from medicare and managed care patients. J Cardiovasc Electrophysiol 2002, 13:38-43.
60.    Schaumann A, et al.: Empirical versus tested antitachycardia pacing in implantable cardioverter defibrillators: a prospective study including 200 patients. Circulation 1998, 97:66-74.
61.    Sim I: Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Circulation 1997, 96:2823-2829.
62.    Smith SCJ, Blair SN, Bono RO, et al. AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update. Circulation. 2001;104:1577–1579.
63.    Spencer FA, Meyer TE, Gore JM, Goldberg RJ. Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure: the National Registry of Myocardial Infarction. Circulation. 2002;105:2605–2610.
64.    Stanton M: Economic outcomes of implantable defibrillators. Circulation 2000, 101:1067-1074.
65.    Stenestrand U, Wallentin L, for the Swedish Register of Cardiac Intensive Care (RIKS-HIA). Early statin treatment following acute myocardial infarction and 1-year survival. JAMA. 2001;285:430–436.
66.    Sueta CA, Chowdhury M, Boccuzzi SJ, et al. Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1999;83:1303–1307.
67.    Schwartz GG, Olsson AG, Ezekowitz MD, et al.Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–1718.
68.    Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993;88:2045– 8.
69.    Tsung SH. Several conditions causing elevation of serum CK-MB and CK-BB. Am J Clin Pathol 1981;75:711–5.
70.    Wathen M, et al.: Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. Circulation 2001, 104:796-801.
71.    Williams DO, Kirby MG, McPherson K, Phear DN. Anticoagulant treatment of unstable angina. Br J Clin Pract 1986;40:114–6.
72.    Wood D, Durrington P, Poulter N, McInnes G, Rees A and Wray R. Joint British recommendations on prevention of coronary heart disease in clinical practice. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, Diabetes UK. Heart 1998;80 (Suppl 2): S1-S29.
73.    Yusuf S. Two decades of progress in preventing vascular disease. Lancet. 2002;360:2–3.
74.    Yusuf S, Peto R, Lewis J, et al. Beta blocker during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–371.
75.    Yusuf S, Sleight P, Pogue J, et al. Effects of 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.
76.    Zaacks SM, Liebson PR, Calvin JE, Parrillo JE, Klein LW. Unstable angina and non–Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol 1999;33: 107–18.
77.    27th Bethesda Conference. Matching the Intensity of Risk Factor Management with the Hazard for Coronary Disease Events. J Am Coll Cardiol. 1996;27:957–1047.
{mospagebreak}
Definition of Related Terminology
Acute coronary syndrome—any constellation of clinical
signs or symptoms suggestive of AMI or UA. This
syndrome includes patients with AMI, STEMI,
NSTEMI, enzyme-diagnosed MI, biomarker-diagnosed
MI, late ECG-diagnosed MI, and UA. This term is
useful to generically refer to patients who ultimately prove
to have 1 of these diagnoses to describe management
alternatives at a time before the diagnosis is ultimately
confirmed. This term is also used prospectively to identify
those patients at a time of initial presentation who should
be considered for treatment of AMI or UA. Probable
acute coronary syndrome is a term that is commonly
used, and this represents the primary consideration of
patients on initial presentation. Possible acute coronary
syndrome is useful as a secondary diagnosis when an
alternate diagnosis seems more likely but an acute ischemic
process has not been excluded as a possible cause of
the presenting symptoms.
Acute myocardial infarction—an acute process of myocardial ischemia with sufficient severity and duration to
result in permanent myocardial damage. Clinically, the
diagnosis of permanent myocardial damage is typically
made when there is a characteristic rise and fall in cardiac
biomarkers indicative of myocardial necrosis that may or
1040 Braunwald et al. JACC Vol. 36, No. 3, 2000
ACC/AHA Guidelines for Unstable Angina September 2000:970–1062
may not be accompanied by the development of Q waves
on the ECG. Permanent myocardial damage may also be
diagnosed when histological evidence of myocardial necrosis
is observed on pathological examination.
Angina pectoris—a clinical syndrome typically characterized
by a deep, poorly localized chest or arm discomfort
that is reproducibly associated with physical exertion or
emotional stress and relieved promptly (i.e., ,5 min) with
rest or sublingual NTG. The discomfort of angina is often
hard for patients to describe, and many patients do not
consider it to be “pain.” Patients with UA may have
discomfort with all the qualities of typical angina except
that episodes are more severe and prolonged and may
occur at rest with an unknown relationship to exertion or
stress. In most, but not all, patients, these symptoms
reflect myocardial ischemia that results from significant
underlying CAD.
Angiographically significant coronary artery disease—
CAD is typically judged “significant” at coronary angiography
if there is $70% diameter stenosis, assessed visually,
of $1 major epicardial coronary segments or $50%
diameter stenosis of the left main coronary artery. The
term “significant CAD” used in these guidelines does not
imply clinical significance but refers only to an angiographically
significant stenosis.
Coronary artery disease—although a number of disease
processes other than atherosclerosis can involve coronary
arteries, in these guidelines, the term “CAD” refers to the
atherosclerotic narrowing of the major epicardial coronary
arteries.
Enzyme- or biomarker-diagnosed acute myocardial
infarction—diagnostic elevation of cardiac enzymes or
biomarkers (e.g., troponin) that indicates definite myocardial
injury in the absence of diagnostic ECG changes
(Q waves or ST-segment deviation).
Ischemic heart disease—a form of heart disease with
primary manifestations that result from myocardial ischemia
due to atherosclerotic CAD. This term encompasses
a spectrum of conditions, ranging from the asymptomatic
preclinical phase to AMI and sudden cardiac death.
Likelihood—used in these guidelines to refer to the
probability of an underlying diagnosis, particularly significant
CAD.
Myocardial ischemia—a condition in which oxygen delivery to and metabolite removal from the myocardium
fall below normal levels, with oxygen demand exceeding
supply. As a consequence, the metabolic machinery of
myocardial cells is impaired, leading to various degrees of
systolic (contractile) and diastolic (relaxation) dysfunction.
Ischemia is usually diagnosed indirectly through
techniques that demonstrate reduced myocardial blood
flow or its consequences on contracting myocardium.
Non–Q-wave myocardial infarction—an AMI that is
not associated with the evolution of new Q waves on the
ECG. The diagnosis of non–Q-wave MI is often difficult
to make soon after the event and is commonly made only
retrospectively on the basis of elevated cardiac enzyme
levels.
Non–ST-segment elevation myocardial infarction—
NSTEMI is an acute process of myocardial ischemia with
sufficient severity and duration to result in myocardial
necrosis (see Acute Myocardial Infarction). The initial
ECG in patients with NSTEMI does not show STsegment
elevation; the majority of patients who present
with NSTEMI do not develop new Q waves on the ECG
and are ultimately diagnosed as having had a non–Qwave
MI. NSTEMI is distinguished from UA by the
detection of cardiac markers indicative of myocardial
necrosis in NSTEMI and the absence of abnormal
elevation of such biomarkers in patients with UA.
Post–myocardial infarction angina—UA occurring
from 1 to 60 days after an AMI.
Reperfusion-eligible acute myocardial infarction—a
condition characterized by a clinical presentation compatible
with AMI accompanied by ST-segment elevation or
new LBBB or anterior ST-segment depression with
upright T waves on ECG.
Unstable angina—an acute process of myocardial ischemia
that is not of sufficient severity and duration to result
in myocardial necrosis. Patients with UA typically do not
present with ST-segment elevation on the ECG and do
not release biomarkers indicative of myocardial necrosis
into the blood.
Variant angina—a clinical syndrome of rest pain and
reversible ST-segment elevation without subsequent enzyme
evidence of AMI. In some patients, the cause of this
syndrome appears to be coronary vasospasm alone, often
at the site of an insignificant coronary plaque, but a
majority of patients with variant angina have angiographically
significant CAD.

Abbreviations
AAFP  American Academy of Family
Physicians
ACC  American College of Cardiology
ACE  angiotensin-converting enzyme
ACEP   American College of Emergency
Physicians
ACEI  angiotensin-converting enzyme
inhibitor
ACIP   Asymptomatic Cardiac Ischemia
Pilot
ACP-ASIM   American College of Physicians–
American Society of Internal
Medicine
ACS  acute coronary syndrome
ACT   activated clotting time
JACC Vol. 36, No. 3, 2000 Braunwald et al. 1041
September 2000:970–1062 ACC/AHA Guidelines for Unstable Angina
ADP   adenosine diphosphate
AHA   American Heart Association
AHCPR   Agency for Health Care Policy
and Research
AMI   acute myocardial infarction
aPTT   activated partial thromboplastin
time
ASA   aspirin
ATACS   Antithrombotic Therapy in
Acute Coronary Syndromes
AV   atrioventricular
BARI   Bypass Angioplasty
Revascularization Investigation
CABG   coronary artery bypass graft
surgery
CABRI  Coronary Angioplasty versus
Bypass Revascularisation
Investigation
CAD   coronary artery disease
CAPRIE   Clopidogrel versus Aspirin in
Patients at Risk of Ischaemic
Events
CAPTURE   c7E3 Fab Antiplatelet Therapy
in Unstable Refractory Angina
CARS   Coumadin Aspirin Reinfarction
Study
CASS   Coronary Artery Surgery Study
CCS   Canadian Cardiovascular Society
CHAMP   Combination Hemotherapy And
Mortality Prevention
cGMP   cyclic guanosine monophosphate
CHF  congestive heart failure
CI    confidence interval
CK    creatine kinase
CLASSICS   CLopidogrel ASpirin Stent
International Cooperative Study
COPD   chronic obstructive pulmonary
disease
CRP   C-reactive protein
cTnI  cardiac-specific TnI
cTnT   cardiac-specific TnT
CURE   Clopidogrel in Unstable angina
to Prevent ischemic Events
DANAMI   DANish trial in Acute
Myocardial Infarction
DATA   Diltiazem as Adjunctive Therapy
to Activase
DAVIT   Danish Study Group on
Verapamil in Myocardial Infarction
DRS   Diltiazem Reinfarction Study
DTS   Duke Treadmill Score
EAST   Emory Angioplasty versus
Surgery Trial
ECG   12-lead electrocardiogram,
electrocardiographic
ED   emergency department
EF   ejection fraction (left ventricle)
EPIC   Evaluation of c7E3 for the
Prevention of Ischemic
Complications
EPILOG Evaluation of PTCA to Improve
Long-term Outcome by c7E3
GPIIb/IIIA receptor blockade
EPISTENT   Evaluation of Platelet IIb/IIIa
Inhibitor for STENTing
ESSENCE   Efficacy and Safety of
Subcutaneous Enoxaparin in
Non–Q wave Coronary Events
FRAXIS   FRAxiparine in Ischaemic
Syndrome
FRIC   FRagmin In unstable Coronary
artery disease study
FRISC   Fragmin during Instability in
Coronary Artery Disease
FRISC II   Fast Revascularization During
Instability in Coronary Artery
Disease
GABI   German Angioplasty Bypass
Surgery Investigation
GISSI-1   Gruppo Italiano per lo Studio
della Sopravvivenza nell’Infarto-1
GISSI-3   Gruppo Italiano per lo Studio
della Sopravvivenza nell’infarto
Miocardico
GP   glycoprotein
1042 Braunwald et al. JACC Vol. 36, No. 3, 2000
ACC/AHA Guidelines for Unstable Angina September 2000:970–1062
GUSTO-II   Global Use of Strategies to Open
Occluded Coronary Arteries-II
HDL   high-density lipoprotein
HERS   Heart and Estrogen/progestin
Replacement Study
HINT   Holland Interuniversity Nifedipine/
metoprolol Trial
HOPE   Heart Outcomes Prevention
Evaluation
HRT   hormone replacement therapy
IABP   intra-aortic balloon pump
IMPACT   Integrilin to Minimise Platelet
Aggregation and Coronary
Thrombosis
IV   intravenous
ISIS   International Study of Infarct
Survival
LAD   left anterior descending coronary
artery
LBBB   left bundle-branch block
LDL   low-density lipoprotein
LMWH   low-molecular-weight heparin
LV   left ventricular, left ventricle
MATE   Medicine versus Angiography in
Thrombolytic Exclusion
MDPIT Multicenter Diltiazem Postinfarction
Trial
MET   metabolic equivalent
MB   cardiac muscle isoenzyme of
creatine kinase
MI   myocardial infarction
MM   skeletal muscle isoenzyme of
creatine kinase
MR   mitral regurgitation
MV˙ O2  myocardial oxygen consumption
NCEP   National Cholesterol Education
Program
NHAAP   National Heart Attack Alert
Program
NHLBI   National Heart, Lung, and Blood
Institute
NSTEMI non–ST-segment elevation
myocardial infarction
NTG   nitroglycerin
OASIS   Organization to Assess Strategies
for Ischemic Syndromes
OR odds ratio
PCI   percutaneous coronary
intervention
PR ECG   PR segment
PRISM   Platelet Receptor Inhibition in
Ischemic Syndrome Management
PRISM-PLUS   Platelet Receptor Inhibition in
Ischemic Syndrome Management
in Patients Limited by Unstable
Signs and Symptoms
PTCA   percutaneous transluminal
coronary angioplasty
PURSUIT   Platelet Glycoprotein IIb/IIIa in
Unstable Angina: Receptor
Suppression Using Integrilin
Therapy
RESTORE   Randomized Efficacy Study of
Tirofiban for Outcomes and
REstenosis
RISC   Research Group in Instability in
Coronary Artery Disease
RITA   Randomized Intervention
Treatment of Angina
RR   relative risk
SHEP   Systolic Hypertension in the
Elderly Program
SHOCK  SHould we emergently
revascularize Occluded
Coronaries for cardiogenic shocK
STEMI   ST-segment elevation myocardial
infarction
STS   Society of Thoracic Surgeons
SVG   saphenous vein graft
TIMI   Thrombolysis In Myocardial Infarction
TIMI 9A and 9B   Thrombolysis and Thrombin
Inhibition in Myocardial Infarction
TnC   troponin C
TnI   troponin I
TnT   troponin T
JACC Vol. 36, No. 3, 2000 Braunwald et al. 1043
September 2000:970–1062 ACC/AHA Guidelines for Unstable Angina
TTP   thrombotic thrombocytopenia
purpura
UA   unstable angina
UFH   unfractionated heparin
UKPDS   UK Prospective Diabetes Study
VA   Veterans Administration
VANQWISH   Veterans Affairs Non–Q-Wave
Infarction Strategies in Hospital
WISE   Women’s Ischemia Syndrome
Evaluation
©Copyright 2003 by RAMAZ MITAISHVILI. All rights reserved. This article may not be reproduced by any means without the prior written permission of the author.