1、5/98Acute Coronary Syndrome5/98Worldwide StatisticsEach year:4 million patients are admitted with unstable angina and acute MI 900,000 patients undergo PTCA with or without stent5/98Myocardial Ischemia Spectrum of presentation silent ischemia exertion-induced angina unstable angina acute myocardial
2、infarction5/98Cumulative 6-month mortality from ischemic heart disease0 1 2 3 4 5 65100152025Months after hospital admissionDeaths/100 pts/monthAcute MIUnstable anginaStable anginaDuke Cardiovascular DatabaseN=21,761;1985-1992Diagnosis on adm to hosp5/98Ischemic Heart Diseaseevaluation Based on the
3、patients history/physical exam electrocardiogram Patients are categorized into 3 groups non-cardiac chest pain unstable angina myocardial infarction5/98Acute Coronary SyndromeIschemic DiscomfortUnstable SymptomsNo ST-segmentelevation ST-segmentelevationUnstable Non-QQ-Waveangina AMI AMIECGAcuteReper
4、fusionHistoryPhysical Exam5/98Acute 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 plaque5/98Unstable Angina-Definition angina at rest(20 minutes)new-onset(2 months)e
5、xertional angina(at least CCSC III in severity)recent(90%4h after infusion discontinuation 30%50%Bleeding-time prolongationat steady state 5x 5x6h after infusion discontinuation 1x 1.4x5/98Fibanincidence of intracranial bleeding Treatment(%)StudyCompound Placebo ActiveHeparinRESTORETirofiban 0.3 0.1
6、EPICAbciximab 0.3 0.1 0.4EPILOGAbciximab 0.0 0.1IMPACT IIIntegrelin 0.07 0.07 0.15The EXCITE Trial InvestigatorsBolusLow doseHigh doseBolus+Infusion5/98Unstable AnginaAnti-platelet Therapy Summary the four“P trials”(PRISM,PRISM-PLUS,PARAGON,PURSUIT)all show reduction of death rate between1.3%and 3.4
7、%-in addition to the benefit of aspirin useful in the management of patients with unstable angina and MI without ST elevation5/98Unstable 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,M
8、D5/98Unstable 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 normal1.Ci
9、rculation 1994;89:81-882.JAMA 1996;276:811-8155/98Unstable AnginaAnti-coagulant Therapy Low-molecular-weight heparinadvantages 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(subc
10、utaneous-qd or bid)no need for monitoring5/98Unstable 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 refract
11、ory ischemia as compared to standard heparinN Eng J Med 1997;337:447-4525/98ESSENCE Trialincidence of death,MI,or recurrent anginaN Eng J Med 1997;337:447-45205101520250510152025heparin Lovenoxheparin Lovenoxn=1564 n=1607n=1564 n=160719.8%16.6%P=0.01923.3%19.8%P=0.016Day 14Day 305/98Unstable Angina
12、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 yearCirculati
13、on 1994;89:1545-15565/98Unstable 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;338:1785-17925/98Unstable
14、 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 groupJ Am Col Cardiol 1996;26:1381-65/98Trials Underway GUSTO-IV(abciximab vs placebo)EXCIT
15、E(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)5/98ReferencesAcute Coronary Syndromes:Unstable angina and Non-Q-wave MI.Pierre Theroux and
16、Valentin Fuster.Circulation 1998:97:1195-1206Aspirin,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 Grou
17、p.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;313:1369-1375.5/98ReferencesAntiplatelet treatmen
18、t 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 thera
19、py in unstable rest angina and non-Q-wave infarction in nonprior aspirin users.Antithrombotic Therapy in Acute Coronary Syndromes Research Group.Circulation 1994;89;81-88Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patient s with unstable angina.Oler S,et al.
20、JAMA 1996;276:811-8155/98ReferencesLow molecular weight heparin versus unfractionated heparin for unstable angina and non-Q wave myocardial infarction.Efficacy and Safety of Subcutaneous Enoxaparin in non-Q-Wave Coronary Events Study Group.N Engl J Med 1997;337:447-452.A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina.PRISM-The Platelet Receptor Inhibition in Ischemic Syndrome Management Study Invistigators N Engl J Med 1998;338:1498-505
