Terapêutica Farmacológica IAM SEM SUPRA ST Terapêutica Farmacológica

Terapêutica Farmacológica Antiagregantes plaquetários; Heparinas: HNF e HBPM; Beta-bloqueadores; Bloqueadores dos canais de cálcio; Nitratos; Hipolipemiantes.

Infarto Agudo do Miocárdio Aspirina na SCA 17.1 6.5 Plac. ASA 5 10 15 20 % of Patients Angina Instável Infarto Agudo do Miocárdio 25 11 Plac. ASA 10 20 30 3.3 1.9 Plac. ASA 1 2 3 4 15 11.8 9.4 10 5 Plac. ASA RISC Group. Lancet Roux et al. JACC ISIS-2. L ancet ISIS-2. Lancet 1990;336:827-30. 1992;19:671-7. 1988;2:349-60. 1988;2:349-60.

Eficácia das doses de Aspirina nos eventos vasculares em pctes de alto risco. Aspirin Dose # Trials OR* (%) Odds Ratio 500–1500 mg 34 19 160–325 mg 19 26 75–150 mg 12 32 <75 mg 3 13 Any aspirin 65 23 The Antithrombotic Trialists’ Collaboration compared data from 65 aspirin trials to examine the effects of aspirin dose on vascular events in high-risk patients (in some trials, the doses of aspirin used were in more than one of the comparisons).[1] Serious vascular events (the primary measure of outcome) included nonfatal MI, nonfatal stroke, death from vascular causes, and death from unknown causes. They found that all doses of aspirin studied reduced the risk for vascular events. The greatest number of trials (34) examined high aspirin doses (500 mg to 1500 mg) and revealed a proportional reduction in vascular events of 19%. Aspirin doses of 160 mg to 325 mg were associated with a 26% proportional reduction in vascular events, whereas 75 mg to 150 mg and <75 mg were associated with reductions of 32% and 13%, respectively. Antithrombotic Trialists’ collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71-86. 0.5 1.0 1.5 2.0 Antiplatelet Better Antiplatelet Worse *Odds reduction. Treatment effect P < 0.0001. Adapted . Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.

Aspirina + HNF vs Aspirina na SCA sem SST Incidência de morte ou IAM – 5 primeiros dias % de pacientes Cohen et al. Circulation 1994;89:81-88. Theroux et al. N Engl J Med 1988;319:1105-1111. RISC Group. Lancet 1990;336:827-830. Meta-análise RR = 0,44 (0,21-0,93)

Incidência de IAM e óbito 30 d. (%) SCA sem supradesnível de ST Benefício da terapêutica tradicional Redução do risco ~50% Redução adicional ~40% Incidência de IAM e óbito 30 d. (%) 20 a 30% 10 a 15% 8% Adaptado de Theroux & Cairns. In: Yusuf et al, eds. Evidence Based Cardiology. London:BMJ Books, 1998:395-

Clopidogrel preveniu 26% mais eventos isquêmicos* do que aspirina** Clopidogrel: Evidência Clínica da Eficácia 25 Clopidogrel preveniu 26% mais eventos isquêmicos* do que aspirina** 26% 20 15 *(MI, ischemic stroke,and vascular death) **Based on the CAPRIE trial 1CAPRIE Steering Committee. Lancet 1996;348:1329-1339. 2Antiplatelet Trialists’ Collaboration. BMJ 1994; 308:81-106. Events Prevented/Year/1,000 Patients 19 24 10 Slide 19L In the CAPRIE study, clopidogrel was compared to aspirin and found to be more effective than aspirin, with an 8.7% relative risk reduction in favor of clopidogrel.1 This is in addition to the 25% risk reduction accepted to be provided by aspirin.2 Clopidogrel prevents 26% more ischemic events* than aspirin.** *(MI, ischemic stroke and vascular death) **Based on the CAPRIE trial and Antiplatelet Trialists’ Collaboration meta-analysis, aspirin can be expected to prevent 19 ischemic events* for every 1,000 patients treated per year.1,2 In contrast, clopidogrel can be expected to prevent 24 ischemic events* for every 1,000 patients treated per year, a 26% difference. 1. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-1339. 2. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106. 5 Aspirin1,2 Clopidogrel1,2 19L 29

CURE – Principais resultados de eficácia Desfecho principal Morte CV, IM, AVC % de pacientes com evento isquêmico recorrente* 10 14 12 4 8 6 2 Os benefícios foram observados em algumas horas e continuaram a aumentar durante os 12 meses RRR de 20% p=0,00009 n=12.562 Tratamento padrão‡ Clopidogrel + tratamento padrão‡ 1 2 3 4 5 6 7 8 9 10 11 12 Meses de seguimento *morte cardiovascular, IM, ou AVC Pesquisadores do CURE. N Eng J Med August 2001

CURE : Resultados de Sangramentos em 1 Ano Eventos Clopidogrel + ASA* n = 6259 Placebo + ASA* n = 6303 P value Sang. maior † 3.7% 2.7% 0.001 Sang. c/ risco vida 2.2% 1.8% 0.13 Outros Sang. maiores 1.6% 1.0% 0.005 Sang. menores 5.1% 2.4% <0.001 The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: < or =100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and > or =200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]).2 The risk of major or minor bleeding was increased for the clopidogrel and aspirin (ASA) group compared with the placebo plus ASA group (major bleeding: 3.7% versus 2.7%, respectively, P = 0.001; minor bleeding 5.1% versus 2.4%, respectively, P < 0.001).1 Major bleeds were increased both early (<30 days) and late (>30 days). The principal sites for major bleeding included gastrointestinal and at arterial-puncture sites.2 The percentage of patients receiving transfusions of 2 or more units of blood was higher in the clopidogrel plus ASA group (2.8% vs 2.2%, P = 0.02).2 Plavix® (clopidogrel sulfate) Prescribing Information. The CURE Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. *Other standard therapies were used as appropriate. †Life-threatening and other major bleeding. The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

Resultados globais a longo prazo † PCI-CURE Resultados globais a longo prazo † Composto de morte cardiovascular ou IM, da randomização ao fim do seguimento † 0.15 Razões de risco cumulativo 12,6% 0,10 0,05 0,0 10 40 100 200 300 400 RRR de 31% p =0,002 n=2658 Dias de seguimento a b a = tempo mediano da randomização à ICP (10 dias) b = 30 dias após tempo mediano de ICP Tratamento padrão ‡ Clopidogrel + tratamento padrão Pesquisadores do CURE. Lancet August 2001 † até 12 meses com AAS 8,8%