急性心肌梗死治疗进展霍勇

急性心肌梗死治疗进展,北京大学第一医院 霍勇 2007年11月23日,急性心肌梗塞治疗的进展,心肌梗塞治疗的关键：,迅速、完全、持续 开通梗塞相关血管,Primary PTCA vs Thrombolysis PAMI Trial: in-hospital mortality,P=0.01,P0.07,65,P=0.03,P=0.01,评估STEMI再灌注方式 -ACC/AHA 2004 STEMI Guidelines,步骤1：评估时间和危险性 症状发作后的时间 STEMI危险分层 溶栓风险 转运至熟练PCI导管室所需时间,JACC August 4, 2004;44:671-719,再灌注策略危险和获益,静脉溶栓 直接PCI,时间 时间,评估STEMI再灌注方式 -ACC/AHA 2004 STEMI Guidelines,步骤2：决定应首选溶栓还是PCI 如果时间少于3小时，且介入治疗无耽搁，溶栓和PCI首选哪种都可以。,JACC August 4, 2004;44:671-719,评估STEMI再灌注方式 -ACC/AHA 2004 STEMI Guidelines,溶栓首选，如果： 早期就诊（症状发作在3小时内，行介入治疗有耽搁） 不适合选择介入治疗 导管室被占用或不能用 血管入路困难 缺乏熟练PCI操作相关工作人员 介入治疗时间耽搁 运输时间延长 Door-to-balloon比door-to-needlle时间超过1小时 或door-to-balloon时间超过90分钟,JACC August 4, 2004;44:671-719,评估STEMI再灌注方式 -ACC/AHA 2004 STEMI Guidelines,PCI首选，如果： 熟练PCI操作相关人员及有心外科支持 Door-to-balloon时间3小时 不能确定STEMI诊断,JACC August 4, 2004;44:671-719,2004年ESC的PCI指南中的AMI再灌注策略,STEMI 病人中ASA+溶栓剂治疗增加的效果,ISIS-2 Collaborative Group. Lancet 1988;2:349-60,在17187例STEMI病人中进行的RCT比较: 链激酶(SK) 、 ASA 1月 、 SK+ASA 、 安慰剂治疗,安慰剂: 588/4300 (13.2%),0,0,血管性死亡的累积病例数,随机分组后的天数,7,14,21,28,35,100,200,300,400,500,600,Aspirin: 461/4295 (10.7%),Streptokinase: 448/4300 (10.4%),Streptokinase aspirin: 343/4292 (8.0%),主要终点指标: 动脉闭塞 (或动脉造影/出院前发生死亡/心梗),Placebo,Clopidogrel,P=0.00000036,Odds Ratio 0.64 (95% CI 0.53-0.76),1.0,0.4,0.6,0.8,1.2,1.6,Clopidogrel better,Placebo better,n=1752,n=1739,36% Odds Reduction,Sabatine et al. NEJM 2005; 352: 1179,COMMIT: 主要终点死亡,0,7,14,21,28,0,1,2,3,4,5,6,7,8,9,Days (up to 28 days),Clopidogrel (7.5%),Placebo (8.1%),RRR=7% p=0.03,Mortality (%),Chen ZM et al. Oral presentation, ACC 2005. Available at: URL: . Accessed April 2005.,STEMI 6 小时符合溶栓指征,医生根据情况选择溶栓剂 (TNK,TPA, rPA, SK),普通肝素 60 U/kg 负荷剂量 12 U/kg/h 维持 48 小时以上,依诺肝素 75 y : 30 mg 负荷剂量 皮下 1.0 mg/kg q12h (出院) 75 y : 无负荷剂量 皮下 0.75 mg/kg q12h (出院) CrCl 30: 1.0 mg/kg q24 h,双盲双模拟期,30天随访 主要有效性终点：死亡或非致命性心梗 主要安全性终点：TIMI严重出血事件,阿司匹林 (ASA),97 % 在溶栓治疗开始30min内接受了研究药物治疗， 中位住院时间10天,N=20,506,TNK: Tenecteplase; TPA: Tissue plasminogen activator; rPA: Reteplase; SK: Streptokinase; UFH: Unfractionated heparin; CrCl: Creatinine clearance,STEMI: ST-segment elevation myocardial infarction; MI:Myocardialinfarction; TIMI:Thrombolysis in Myocardial Infarction,Primary End Point (ITT) Death or Nonfatal MI,Primary End Point (%),ENOX,UFH,Relative Risk 0.83 (0.77 to 0.90) P0.0001,Days,9.9%,12.0%,Lost to follow up = 3,17% RRR,在预先定义的各个亚组中， 依诺肝素组显示出一致的疗效,0.5,1 相对风险,2,依诺肝素更优,普通肝素更优,风险降低（）,依诺肝素,普通肝素,The overall treatment effect of enoxaparin versus UFH is shown with the diamond symbol (left and right edges represent 95% confidence interval) and the dotted vertical line,出现终点事件的患者 (%),30天结果: 氯吡格雷联合依诺肝素疗效更好,事件发生率（）,12.2,11.4,绝对风险下降15,绝对风险下降24,P值,0.0005,0.0006,n=14,752(78%),n=5,727(28%),CADILLAC: MACE - 6 Months,0%,5%,10%,15%,20%,0,30,60,90,120,150,180,Days to event,15.2%,19.3%,10.8%,10.9%,Stone GR, et al. Presented at the AHA 72nd Scientific Sessions. 1999 A.II.030,TLR、TVR、MACE和TVF的发生危险分别下降：61%、62%、59%和53%.,OAT Trial: Study Design,Primary Endpoints: Death, MI, or NYHA class IV heart failure,PCI with stenting n=1082,Medical Therapy n=1084,2166 patients with angiography on day 3-28 post-MI revealing total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and meeting a criterion for increased risk: defined as ejection fraction 50%, proximal occlusion of a major epicardial vessel with a large risk region, or both,OAT研究引起的思考,Randomized,OAT Trial: Primary Endpoint,Primary Endpoint of death, reinfarction, NYHA class IV heart failure (% patients) Hazard Ratio 1.16, p=0.20,Hochman JS et al. N Engl J Med. 2006; 355(23):2395-407. Presented at AHA 2006,OAT研究结果质疑,入选时间过长，入选患者人数较少导致研究效力下降 入选的患者仅仅占众多AMI患者的极小一部分 研究长期临床随访率较低:8% Slow/No-Reflow发生率高达18： 研究对象多为存活心肌较少的患者 仅有8的患者使用了药物洗脱支架。,Cardiac Cell Therapy and STEAMI,Randomized-controlled BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial,Intracoronary autologous BMC transfer improves echocardiographic parameters of diastolic function in patients after AMI.,Circulation. 2006 Mar 14;113(10):1287-94.,Cardiac Cell Therapy and STEAMI,ASTAMI TRIAL,No effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.,N Engl J Med 2006; 355: 11991209.,Cardiac Cell Therapy and STEAMI,REPAIR-AMI TRIAL,Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction.,N Engl J Med 2006; 355: 1210 1221,Cardiac Cell Therapy and STEAMI,Intracoronary infusion of PBMNCs in patients with AMI is associated with improved global LV contractile function.,Cell therapy preferentially improves LV function in patients with early reperfusion,Circulation Journal Vol.71, August 20