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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,5/98,MedS,Acute Coronary Syndrome,5/98,MedS,Acute Coronary Syndrome5/98Med,Worldwide Statistics,Each year:, 4 million patients are admitted with unstable angina and acute MI, 900,000 patients undergo PTCA with or without stent,5/98,MedS,Worldwide StatisticsEach year:,Myocardial Ischemia,Spectrum of presentation,silent ischemia,exertion-induced angina,unstable angina,acute myocardial infarction,5/98,MedS,Myocardial IschemiaSpectrum of,Cumulative 6-month mortality from ischemic heart disease,0 1 2 3 4 5 6,5,10,0,15,20,25,Months after hospital admission,Deaths / 100 pts / month,Acute MI,Unstable angina,Stable angina,Duke Cardiovascular Database,N = 21,761; 1985-1992,Diagnosis on adm to hosp,5/98,MedS,Cumulative 6-month mortality,Ischemic Heart Diseaseevaluation,Based on the patients,history / physical exam,electrocardiogram,Patients are categorized into 3 groups,non-cardiac chest pain,unstable angina,myocardial infarction,5/98,MedS,Ischemic Heart Diseaseevaluat,Acute Coronary Syndrome,Ischemic DiscomfortUnstable Symptoms,No ST-segmentelevation,ST-segmentelevation,Unstable Non-QQ-Waveangina AMI AMI,ECG,AcuteReperfusion,HistoryPhysical Exam,5/98,MedS,Acute Coronary SyndromeIschemi,Acute Coronary Syndrome,The spectrum of clinical conditions ranging from:,unstable angina,non-Q wave MI,Q-wave MI,characterized by the common pathophysiology of a disrupted atheroslerotic plaque,5/98,MedS,Acute Coronary SyndromeThe spe,Unstable Angina - Definition,angina at rest ( 20 minutes),new-onset ( 2 months) exertional angina (at least CCSC III in severity),recent (90%,4h after infusion discontinuation 30% 50%,Bleeding-time prolongation,at steady state 5x 5x,6h after infusion discontinuation 1x 1.4x,5/98,MedS,Platelet Inhibition and Bleedi,Fibanincidence of intracranial bleeding,Treatment (%),StudyCompound Placebo ActiveHeparin,RESTORETirofiban 0.3 0.1,EPICAbciximab 0.3 0.1,0.4,EPILOGAbciximab 0.0 0.1,IMPACT IIIntegrelin 0.07 0.07 0.15,The EXCITE Trial Investigators,Bolus,Low dose,High dose,Bolus + Infusion,5/98,MedS,Fibanincidence of intracrania,Unstable AnginaAnti-platelet Therapy,Summary,the four “P trials”,(PRISM, PRISM-PLUS, PARAGON, PURSUIT),all show reduction of death rate between,1.3%,and,3.4%,- in addition to the benefit of aspirin,useful in the management of patients with unstable angina and MI without ST elevation,5/98,MedS,Unstable AnginaAnti-platelet,Unstable AnginaAnti-platelet Therapy,Summary,The question is no longer,“Is there a reason to use GP IIb/IIIa inhibitors?” but “Is there a reason not to use them?”,Eric Topol, MD,5/98,MedS,Unstable AnginaAnti-platelet,Unstable AnginaAnti-coagulant Therapy,Heparin,recommendation is based on documented efficacy in many trials of moderate size,meta-analyses,(1,2),of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding,titrate PTT to 2x the upper limits of normal,1. Circulation 1994;89:81-88,2. JAMA 1996;276:811-815,5/98,MedS,Unstable AnginaAnti-coagulant,Unstable AnginaAnti-coagulant Therapy,Low-molecular-weight heparin,advantages over heparin:,better bio-availability,higher ratio (3:1) of anti-Xa to anti-IIa activity,longer anti-Xa activity, avoid rebound,induces less platelet activation,ease of use (subcutaneous - qd or bid),no need for monitoring,5/98,MedS,Unstable AnginaAnti-coagulant,Unstable Angina Anti-coagulant Therapy,Low-molecular-weight heparin,ESSENCE Trial,(Efficacy and Safety of Subcutaneous Enoxaparin in non-Q-Wave Coronary Events Study),at 30days, there was a relative risk reduction of,15% -16%,in the rate of death, MI, or refractory ischemia as compared to standard heparin,N Eng J Med 1997;337:447-452,5/98,MedS,Unstable Angina Anti-coagulan,ESSENCE Trial,incidence of death, MI, or recurrent angina,N Eng J Med 1997;337:447-452,heparin Lovenox,heparin Lovenox,n=1564 n=1607,n=1564 n=1607,19.8%,16.6%,P=0.019,23.3%,19.8%,P=0.016,Day 14,Day 30,5/98,MedS,ESSENCE Trialincidence of dea,Unstable Angina Coronary Interventions,TIMI 3B,early intervention vs conservative strategy(coronary angiography within 24-48 hrs, followed by angioplasty or bypass surgery),1473 patients with UA or non-Q-wave MI were randomized, there were no difference between the groups in the rates of death or MI at 1 year,Circulation 1994;89:1545-1556,5/98,MedS,Unstable Angina Coronary Inte,Unstable Angina Coronary Interventions,VANQWISH,(Veteran Affairs non-Q-Wave Infarction Strategies in Hospital),better outcome with initial conservative therapy with lower rates of death and MImedicalinvasiveHosp discharge 3% 8%One year 18.5% 24%,NEJM 1998;338:1785-1792,5/98,MedS,Unstable Angina Coronary Inte,Unstable Angina role of non-ionic contrast,Ionic contrast media seem to perform better in ACS,prospective, randomized control trial of 211 patient,a much greater need for CABG was seen in the non-ionic contrast medium group,J Am Col Cardiol 1996; 26:1381-6,5/98,MedS,Unstable Angina role of non-i,Trials Underway,GUSTO-IV,(abciximab vs placebo),EXCITE,( Eval of Oral Xemilofiban in Controlling Thrombotic Events),OPUS,(Orofiban in Patients with Unstable Coronary Syndromes),SYMPHONY,(Sibrafiban vs Aspirin to Yield Maximum Protection from Ischemic Events Post ACS),5/98,MedS,Trials UnderwayGUSTO-IV (abcix,References,Acute Coronary Syndromes: Unstable angina and Non-Q-wave MI. Pierre Theroux and Valentin Fuster.,Circulation 1998:97:1195-1206,Aspirin, heparin, or both to treat acute unstable angina.TherouxP, et al.,N Eng J Med. 1988;319:1105-1111.,Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary disease. The RISC Group.,Lancet 1990;336:827-830.,Protective effects of aspirin against myocardial infarction and death in men with unstable angina.Lewis HD, et al.,N Eng J Med. 1983;309:396-403.,Aspirin, sulfinpyrazone, or both in unstable angina.Cairns JA, et al.,N Eng J Med. 1985;313:1369-1375.,5/98,MedS,ReferencesAcute Coronary Syndr,References,Antiplatelet treatment with ticlopidine in unstable angina: a controlled multicenter clinical trial. Balsano F, et al.,Circulation 1990;82:17-26.,A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events.CAPRIE Steering Committee.,Lancet 1996;348:1329-1339.,Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users.Antithrombotic Therapy in Acute Coronary Syndromes Research Group.,Circulation 1994;89;81-88,Adding heparin to aspirin reduces the incidence of myocard
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