1、急性心肌梗塞治疗的进展,急性心肌梗塞治疗的进展,急性心肌梗塞治疗的目标:,缩小梗塞面积保护心功能防治併发症降低死亡率,心肌梗塞治疗的关键：,迅速、完全、持续 开通梗塞相关血管,一、再灌注治疗,急性心肌梗塞的再灌注治疗:,溶栓治疗,THROMBOLYTIC THERAPY,Rationale - atherosclerotic plaque rupture; - thrombus formation; - total or subtotal occlusion; - slow spontaneous lysis; - fibrinolysis,ISIS-2试验,The ISIS-2 collab
2、orative group. Lancet 1988; ii: 34960,溶栓是最佳选择,急性心肌梗塞治疗的进展,Thrombolytic therapywell documented benefit from thrombolytic therapy ISIS GUSTO GISSI SAMI-ECSG TAMI WWICST ASSET APSAC AMIS EMIP,FTT试验年龄相关溶栓与死亡率的关系,FTT Collaborative Group. Lancet. 1994;343:311-322.,THROMBOLYTIC THERAPY,Benefit - 1/3 reduct
3、ion in overall mortality - 40-50 fewer death / 1000 patients treated - Less remodelling / dilatation of LV better LV function - Less arrhythmia - Improved short- and long-term survival,急性心肌梗塞治疗的进展,Greater Benefit from earlier treatment,急性心肌梗塞治疗的进展,Clear benefit up to 12 hrs from symptom onset,急性心肌梗塞
4、治疗的进展,Lack of difference in net clinical outcome with different thrombolytic regimens,冠心病诊断和治疗新进展,急性心肌梗死治疗的溶栓治疗有效性已被很多的大规模、多中心的实验证实（GISSI-1、ISIS-2、ASSET）时间=心肌=生命没有某种溶栓剂明显优于其它溶栓剂GUSTO：加速tPA6.3%，链激酶7.3%,冠心病诊断和治疗新进展,溶栓治疗时间窗扩大：LATE试验显示612小时内溶栓，死亡率下降25%，1224小时则无效院前使用,急性心肌梗塞治疗的进展,P=0.001,急性心肌梗塞治疗的进展,*GUST
5、O Angiographic Investigators: N Engl J Med 1993;329:1615-22,P=0.001,P=NS,急性心肌梗塞治疗的进展,Coronary artery patency at 90 min and 30-day mortality in GUSTO-1,*p0.05 relative to TIMI grade 0-1,再灌注治疗策略：溶栓治疗,溶栓治疗不足之处再通率为6080%且残留狭窄再通者中达TIMI血流3级者约为5060%再通者中，TIMI血流2级者再梗塞率高临床缺少可靠再灌注指标不是全部AMI患者都适合于溶栓(约25%)12%出血并发症
6、心肌缺血发生率高心源性休克效果差,溶栓治疗的好处有效对设备和人员培训要求低方便，迅速应用广泛应用,急性心肌梗塞的再灌注治疗:,二、直接PCI治疗,Treatment = Reperfusion,PAMI试验结果,PAMI试验：395例入选，AMI发病6小时以内,r-tPA（ %） PTCA（%）,死亡率 6.5 2.6高危者死亡率 10.4 2.6再梗/院内死亡 12.0 5.1颅内出血 0.5 0,Primary PTCA vs Thrombolysis PAMI Trial: in-hospital mortality,P=0.01,P65,P=0.03,P=0.01,GUSTO IIb试
7、验,对比直接PTCA与溶栓治疗对AMI的临床疗效，入选1138例发病后12小时内的AMI患者，观察30天内死亡、再次MI和致残性卒中的联合发生率结论：在有经验的临床中心，直接PTCA的近中期疗效优于t-PA溶栓,死亡 再次MI 卒中 联合发生率,P=0.37 P=0.13 P=0.11 P=0.033,N Engl L Med, 1997,336:1621-1628,PCI是最佳选择,STOPAMI试验,Schomig et al. N Engl J Med 2000;343:385-91Kastrati et al. Lancet 2002;359:920-25,CADILLAC:MACE
8、- 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,Primary PTCA vs Thrombolytic Therapy,For every 1000 pts treated, PTCA compared with lytic therapy:20 lives saved43 re-MI prevented13
9、 ICH prevented,Meta-analysis of 23 trials suggests that primary PTCA is preferred over lytic therapy,Keely et al. Lancet 2003,直接PTCA的优点,成功率高，9095%降低脑卒中的发生率降低反复心肌缺血减低再次住院和死亡缩短住院时间增加EF,Cardiogenic shock and Primary PTCA,SHOCK Trial: ERV 组 Med 组 p病例数 152 15030天死亡率 46.7% 56% 0.1160天死亡率 50.3% 63.1% 0.27
10、75 y 效果更差,AMI的直接PCI治疗：高危患者获益更大,四个亚组疗效优于溶栓组心源性休克前壁心梗心衰老年人70岁,直接PCI与溶栓治疗：长期疗效,直接PTCA对设备和医生的要求：,图象质量极佳的X光设备操作者技术优良工作人员快速反应：门口气囊时间最好小于1小时，不能大于2小时对AMI能快速作出诊断最好能备有 GPb/a受体拮抗剂,再灌注治疗策略：直接PCI,不足之处对设备和人员培训要求高治疗廷迟(平均医院-气囊时间为120分钟)没有被广泛应用,好处更有效，更高的再灌注率(80%以上达TIMI3级)颅内出血少早期了解冠脉病理解剖和左室功能,Reperfusion Therapy in Pa
11、tients with STEMIin Registry Studies 1999-2003,0%,10%,20%,30%,40%,50%,60%,70%,80%,Sweden,RIKS-HIA,Italy,BLITZ,USA,NRMI-4,Euro Heart,Survey,ENACT,GRACE,Int.,Thrombolysis,Primary PCI,急性心肌梗塞的再灌注治疗:,三、溶栓失败后补救性PCI治疗,补救性PCI 2年存活随访,Gibson et al. Circulation 2002;105:1909-13,Ellis SG, et al. Circulation. 19
12、94;90:2280-2284.,The Rescue Trial,151 pts with first anterior MI treated with fibrinolytic therapySubsequently randomized to conservative therapy (ASA, heparin, vasodilator) vs therapy plus PTCAPTCA vs conservative therapy92% technical success with PTCAExercise LV function improved (43% + 15% vs 38%
13、 + 13%, P=0.04)Mortality reduced by 50% in the PTCA-treated group (5% vs 10%; P=0.18)Mortality and severe heart failure reduced by 64% in PTCA-treated group (6% vs 17%; P=0.05),A.II.030,Resue PTCA after failed fibrinolysis RESCUE I trial,PTCA,No PTCA,P=0.001,12,6,0,62,36,24,48,0.6,0.7,0.8,0.9,1.0,Ti
14、me,(weeks),Ellis, Am Heart J 2000; 139:1046,A.II.030,% Survival,四、首诊到基层医院的AMI病人，应采取何种再灌注策略：溶栓治疗？直接PCI？,AMI:转院进行直接PCI？,存在溶栓禁忌，梗塞面积较大 -YES！溶栓失败，12小时内 -YES！心源性休克，36小时内 -YES！没有溶栓禁忌，时间窗以内 -？,The PRAGUE Study (N=300),p0.001,23.0%,15.0%,8.0%,The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2),A to
15、tal of 1900 patients with ST-elevation myocardialinfarction are to be randomized 800 patients will be admitted to invasive hospitals 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to
16、 be treated with primary angioplasty.,STEMI随机,溶栓组（100mg tPA）,直接PCI组,Anderson HR, et al. N Engl J Med. 2003; 349: 733742,DANAMI 2,5,400,000人5个PCI中心24家医院占丹麦总人口的62%转运距离最远95公里平均31公里,Anderson HR, et al. N Engl J Med. 2003; 349: 733742,支持转院行PCI,DANAMI 2,Anderson HR, et al. N Engl J Med. 2003; 349: 733742,
17、支持转院行PCI,The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2),p=0.002,P=0.05,DANAMI 2,Anderson HR, et al. N Engl J Med. 2003; 349: 733742,支持转院行PCI,The PRAGUE-2 Study (N=850),胸痛12h溶栓组n=421转院PCI n=429主要终点：30天死亡率次要终点：30天死亡/再梗/中风距离3小时病人死亡率,-6项对比研究-3750例病人-转院时间3小时,溶栓Vs转院PCI:荟萃分析,结论：转院PCI优于当地溶栓,P=
18、0.08,P=.015,P.001,P.001,转院的可行性和安全性 PRAGUE 1 + 2试验,共转运626 例病人转运距离: 5 120 km共死亡2 例(0.3%)转运期间共5例 发生VFs (0.8%)因此，转院是安全、可行的,支持转院行PCI,再灌注策略危险和获益,静脉溶栓 直接PCI,时间 时间,讨论,转院途中的安全性 -死亡率低，50%使用6个月，EF50%长期使用-受体阻滞剂：可使再梗塞下降30%他丁类降胆固醇药物：多个试验证实有效AABC方案,冠心病诊断和治疗新进展,药物治疗硝酸酯类药物：ISIS-4试验、GISSI-3试验结果阴性抗心律失常药物治疗：CAST实验：c类抗心
19、律失常药物使死亡率增加,急性心肌梗塞治疗的进展,其它药物硝酸酯类药物：ISIS 4、GISSI 3钙拮抗剂：双氢吡啶类可增加死亡率抗心律失常药：CAST试验镁剂：ISIS 4,三、高危病人的诊断与治疗,四、未来发展趋势,急性心肌梗塞治疗的进展,未来展望血管再通最佳方法：溶栓治疗？直接PTCA？超级溶栓剂？,STEMI的现代再灌注治疗,救护系统：救护车配备心电图机,ECG明确STEMI:ASA+UFH+PLAVIX与PCI中心联系运送病人过程中导管室做好准备,直接送达导管室（不经过急诊室或CCU),直接行CAG和PCI,STEMI治疗的区域系统,救护车,非PCI医院,PCI医院,建立起区域性的绿
20、色通道,小结,迅速、完全、持久开通IRA是心梗治疗的关键直接PCI临床疗效优于溶栓治疗，但目前在我国溶栓治疗仍是主导治疗方法AABC可改善心梗病人预后今后应研究理想的溶栓药物,谢谢,AMI treatment: Reperfusion therapy,Thrombolytic therapyDirect angioplastyRescue angioplastyTransfer angioplasty,THROMBOLYTIC THERAPY,Rationale - atherosclerotic plaque rupture; - thrombus formation; - total or
21、 subtotal occlusion; - slow spontaneous lysis; - fibrinolysis,急性心肌梗塞治疗的进展,Thrombolytic therapywell documented benefit from thrombolytic therapy ISIS GUSTO GISSI SAMI-ECSG TAMI WWICST ASSET APSAC AMIS EMIP,THROMBOLYTIC THERAPY,1/3 reduction in overall mortality40-50 fewer death / 1000 patients treate
22、dLess remodeling / dilatation of LV better LV functionLess arrhythmia Improved short- and long-term survival,急性心肌梗塞治疗的进展,Greater Benefit from earlier treatment,-有效性已被很多的大规模、多中心的实验证实（GISSI-1、ISIS-2、ASSET） -时间=心肌=生命 -没有某种溶栓剂明显优于其它溶栓剂GUSTO：加速tPA6.3%，链激酶7.3%,急性心肌梗死治疗的溶栓治疗,AMI的溶栓治疗,时间窗扩大：LATE试验显示612小时内溶栓
23、，死亡率下降25%，1224小时则无效院前使用,Coronary artery patency at 90 min and 30-day mortality in GUSTO-1,*p3小时的病人,小结2,将AMI病人集中到大医院治疗是未来国际上的重大趋势应重新思考我国城市/城市邻近地区的AMI再灌注治疗模式应进一步PCI前是否需联合用药，Lysis? GPII/bIIIa? 其他?,谢谢！,急性心肌梗塞的介入治疗,支架 PTCA6个月无心脏事件率 95% 80%再次心梗 1% 7% TVR 4% 17%24个月随访 12% 30%死亡、心梗及TVR棗Circulation 1998；97：1
24、202-5,H. Suryapranata：,急性心肌梗塞治疗的进展,Cumulative in-hospital outcome differences between patients treated with stents and those treated with PTCA during AMI,Activation Multiple agonists generated at the site of vascular injury induce platelet activation, which cause GP IIb/IIIa receptors to change to a
25、 fibrinogen binding-receptive state.,急性心肌梗塞治疗的进展,30-day outcomes with bailout stenting in glycoprotein b/a inhibitor trials,AMI 12小时内发病，ECG见ST，或LBBB,Aspirin 300mg，Betaloc， 肝素？,紧急冠脉造影及PTCA,使用溶栓剂,CCU,反复胸痛血流动力学不稳定,休克或肺水肿,溶栓禁忌,适合溶栓,.急性心肌梗塞的治疗程序,急性心肌梗塞治疗的进展,急性心肌梗塞治疗的进展,急性心肌梗塞治疗的进展,TIMI-14 chest pain 12hrs 99(21):2720-32,+,+,急性心肌梗塞治疗的进展,*Antman EM: Circulation 1999;99(21):2720-32,急性心肌梗塞治疗的进展,*Antman EM: Circulation 1999;99(21):2720-32,P=0.009,P=0.02,急性心肌梗塞治疗的进展,TIMI-14结论 ReoPro 可增加rtPA疗效ReoPro及tPA与极小剂量肝素合用，出血并发症低（1%）,
