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1、那些病人能从GP IIb/IIIa Inhibitors获益,中国医学科学院北京协和医学院心血管病研究所阜外心血管病医院袁晋青,主要内容,Characteristics of GP IIb/IIIa InhibitorsGP IIb/IIIa Inhibitors in ACSGP IIb/IIIa Inhibitors in STEMIGPIIb/IIIa Inhibitors and PCI,一、Characteristics of GP IIb/IIIa Inhibitors,Topol E,et al.Lancet.1999;353:227-231.,Abciximab,Eptifib
2、atide,Tirofiban,Fab fragment of a chimeric monoclonal antibodyMW 50,000 D,Nonpeptide tyrosine derivative MW 500 D,Cyclic heptapeptide MW 800 D,鼠源性单克隆抗体,合成非肽类,合成肽类,三种静脉GPb/a受体抑制剂的比较,White HD.Am J Cardiol.1997;80(4A):2B-10B.,GP IIb/IIIa 受体拮抗剂作用机制,Restingplatelet,Plaquerupture andplateletadhesion,Plate
3、letactivation,Prevention of plateletaggregation,GP IIb/IIIaexpression,Fibrinogen,GP IIb/IIIainhibitor,vWF,vWF,vWF,Agonists,released,Vessel Wall,三种静脉GPb/a受体抑制剂的比较,二、GP IIb/IIIa Inhibitors in ACS,GP IIb/IIIa Inhibitors in ACS,The Prism-Plus Investigators.NEJM 1998;338:1488-97,-Death or MI at 30 days-,
4、OR 0.700.51,0.96P=0.03,The PURSUIT Investigators.NEJM 1998;339:436-43,OR 0.900.75,0.98P=0.04,16.7%,15.6%,14.5%,11.6%,0%,5%,10%,15%,20%,Heparin,Eptifibatide+Heparin,Impact of Early PCI on 30 Day Death/MI,10.2%,10.1%,7.8%,5.9%,0%,5%,10%,15%,Heparin,Tirofiban+Heparin,PRISM Plus,PURSUIT,DM,Non-DM,5%,10%
5、,6.2%,Placebo,GPIIb/IIIa Inhibitor,4.6%,P=0.007,3.0%,3.0%,P=NS,GPIIb/IIIa Inhibitors in ACS30-Day mortality results of a Meta-analysis*,Circulation 2001;104:2767-71,*PRISM,PRISM-PLUS,PARAGON A&B,PURSUIT,GUSTO-IV,n=6,458,n=23,072,PCI,No PCI,5%,10%,4.0%,Placebo,GPIIb/IIIa Inhibitor,1.2%,P=0.002,6.7%,5
6、.5%,P=0.1,GPIIb/IIIa Inhibitors in Diabetic Patients with ACS,Circulation 2001;104:2767-2771,30-Day Mortalityof a Meta-analysis*,n=1,279,n=5,179,*PRISM,PRISM-PLUS,PARAGON A&B,PURSUIT,GUSTO-IV,GUSTO-IV Study Design,Non ST-segment elevation ACSMedical rx only planned(no angio or PCI)(n=7800),2590 ASA+
7、UFH+Abciximab24h,2598ASA+UFH or LMUH+placebo,2612 ASA+UFH+Abciximab48h,2598,2590,2612,Lancet 2001;357:1915-24,P=0.664,P=0.235,P=0.190,GUSTO-IV30-Day outcomes,Lancet 2001;357:1915-24,3.9%,5.1%,8.0%,8.2%,5.6%,3.4%,4.3%,5.9%,9.1%,0%,2%,4%,6%,8%,10%,Death,MI,placebo,Abciximab 24h,Abciximab 48h,Death,MI,
8、*p 0.05,vs placebo,*,*,*,*,100,000 per L,50,000 per L,GUSTO-IV safety outcomes,Lancet 2001;357:1915-24,*,Benefits of GP IIb/IIIa Inhibitors by Troponin Status in Clinical Trials,Circulation 2001;103:2891-96,TnT-Negative,TnT-Positive,PARAGON-B,PRISM,CAPTURE,Combined,0.125,1,2,0.5,0.125,1,2,0.5,GP IIb
9、/IIIaBetter,GP IIb/IIIaWorse,GP IIb/IIIaBetter,GP IIb/IIIaWorse,ISAR-REACT 2 Death,MI,or urgent TVR in Subsets With and Without Elevated Troponin Levels(0.03 g/L),0,5,10,15,20,25,30,Days After Randomization,Placebo Group(N=1010)Abciximab Group(N=1012),Troponin 0.03 g/LLog-Rank p=0.02,Troponin 0.03 g
10、/LLog-Rank p=0.98,JAMA 2006;295:1531-38,%,早期应用有效降低住院死亡率NRMI注册研究,NRMI-NSTEMI Risk Score,N=60770NSTEMI患者,住 院 死 亡 率%,NRMI=National Registry of Myocardial Infarction.Peterson E,et al.J Am Coll Cardiol.2003;42:45-53,30天死亡/心梗绝对下降(%),1.7%,2.3%,用 药 距 离 发 病 的 时 间,越早用药 绝对获益越大 PURSUIT研究：GPIIb/IIIa VS 安慰剂,JAMA.
11、2000;284:1549-1558,2009年中国PCI治疗指南GPb/a受体拮抗剂推荐,三、GP IIb/IIIa Inhibitors in STEMI,%,GP IIb/IIIa Inhibitors in STEMI,Abciximab and PCI in STEMI Trials30 Day Endpoint(D,Re-MI,u-TVR),p=0.023,p0.05,p=0.005,PTCA N=483,Stent N=401,Stent N=301,PTCA or Stent N=2082,Stent N=400,p=0.038,p=0.01,RAPPORTAbciximab
12、in primary PTCA for STEMI,9.9%,3.3%,5.0%,2.1%,5.4%,1.2%,P=0.003,p=0.098,P=0.01,Circulation 1998;98;734-741,7-day Outcome,RAPPORT,11.2%,5.8%,5.8%,4.6%,6.6%,1.7%,P=0.03,P=0.52,P=0.006,30 Day follow-up,Circulation.1998;98:734-741,28.1%,28.2%,17.8%,11.6%,11.2%,8.7%,P=0.9,P=0.048,P=0.36,Circulation.1998;
13、98:734-741,RAPPORT6 month follow-up,Primary PTCA(n=518),MultiLink stent+Abciximab(n=524),Primary PTCA+Abciximab(n=528),MultiLink stent(n=512),randomization,CADILLAC,AMI 12 h,cardiogenic shock excluded N=208276 centers in N.A.S.A.and Europe,N Engl J Med 2002;346:957-966,CADILLACKaplan-Meier Estimates
14、 of the Clinical Outcomes at 30 Days and 6 Months,N Engl J Med 2002;346:957-966,CADILLAC30 day acute thrombosis,P=0.05,P=0.03,N Engl J Med 2002;346:957-966,CADILLAC thrombocytopenia and bleeding evnts,PTCAPTCA/AbcxStentStent/AbcxpBleeding-sever0.6%0.2%0.4%0.8%0.58-moderate2.5%2.3%4.3%2.5%0.18-intrcr
15、anial0%0%0%0.2%0.99thrombocytopenia1.4%4.0%2.6%4.0%0.02Blood-product intrafusion3.7%5.1%4.1%5.0%0.62,N Engl J Med 2002;346:957-966,ADMIRAL研究,300 患者，AMI 12 小时在急诊支架置入前，随机接受阿昔单抗，并与安慰剂比较,P0.05,P=NS,P=NS,P0.05,Circulation 2001;103:2328-2335,PRISM-PLUS Angiographic Substudy:Tirofiban Increased Perfusion S
16、tatus,P=0.002 for trend by proportional odds model,Zhao X-Q,et al.Circulation.1999;100:1609-1615.,GPIIb/IIIa受体拮抗剂治疗建议,中高危NSTE-ACS患者(尤其TnT、ST或糖尿病)，可在氯吡格雷+ASA基础上，加用GPIIb/IIIa拮抗剂不建议STEMI患者溶栓时联合应用GPIIb/IIIa受体拮抗剂，尤其是年龄大于75岁的患者GPIIb/IIIa拮抗剂应在抗凝治疗基础上应用(UFH或LMWH)出血危险较高患者慎用或禁忌；若应用GPIIb/IIIa受体拮抗剂，应监测血红蛋白和血小板计
17、数,2009年中国PCI治疗指南GPb/a受体拮抗剂推荐,四、GPIIb/IIIa Inhibitors and PCI,Placebo better,GPI better,0,0.5,1,1.5,2,0.62(0.55,0.71)p 0.000000001,16,770,8.8%,5.6%,GPIIb/IIIa Inhibitors and PCImeta-Analysis,30-day MI/death,EPISTENT1-year results in diabetes,*P0.11,*P0.005,*P0.022,*P0.035,P0.440,P0.290,P0.389,P0.546,
18、stent+placebo VS angiolpasy+abciximab*stent+placebo VS stent+abciximab,Lancet 1999;354:2019-24,EPISTENT,Lancet 1999;354:2019-24,1-year mortality,0,30,60,90,120,150,180,210,240,270,300,330,360,p=0.037,1.0%,2.4%,2.1%,stent+placebo,stent+Abciximab,angioplasty+Abciximab,(days),Follow-up,Lancet 1999;354:
19、2019-24,*P0.156,*P0.001,*P0.002,*P0.369,P0.852,P0.084,P0.062,P0.014,EPISTENT1-year results in non-diabetes,stent+placebo VS angiolpasy+abciximab*stent+placebo VS stent+abciximab,N Engl J Med 2001;344:1888-94,TARGET Tirofiban vs Abciximab in PCI30-day results,0.0,0.5,1.0,1.5,2.0,1.26,2.43,1.26,1.27,1
20、.21,1.26,2.80,Tirofiban better,Abciximab better,TARGET Tirofiban vs Abciximab in PCI 6-month follow-up,N Engl J Med 2001;344:1888-94,ISAR-REACT abciximab in elective PCI,%,0.3,0.4,3.3,0.9,0.3,0.5,3.3,0.7,0,1,2,3,4,5,Death,Q-MI,NQ-MI,Urgent TVR,J Am Coll Cardiol 2004;44:2133-36,exclude recent MI,ACS,
21、diabetes,ALL=NS,abciximab,placebo,%,P=0.38,P=0.007,P=0.002,P=0.37,1.1,2.5,0.9,2.4,0.7,1.9,0,0.9,0,1,2,3,4,5,major bleeding,minor bleeding,transfusion,J Am Coll Cardiol 2004;44:2133-36,abciximab,placebo,thrombocytopenia,ISAR-REACT abciximab in elective PCIsafety outcomes,ASA,clopidogrel,randomization
22、 in cath lab,Placebo+Heparin 60U/kg bolus(ACT 200-300 sec),Eptifibatide180+180 g/kg bolus(boluses 10 min apart)2.0 g/kg-min infusion18-24o+Heparin 60 U/mg bolus(ACT 200-300sec),48 hour,30day,6 month,1 year follow-up,Elective PCI,VS.,Lancet 2000;356:2037-44,ESPRIT,RR=0.62,P=0.0014,6.4%,10.2%,ESPRIT e
23、ptifibatide in elective PCI 30-Day results,Lancet 2000;356:2037-44,Death or MI(%),Days following randomization,0%,2%,4%,6%,8%,10%,12%,10,20,30,Placebo,Eptifibatide,*p0.03,*,*,Major bleeding(TIMI),Lancet 2000;356:2037-44,*,*,ESPRIT30-Day Stroke and bleeding,%,p=.047,EPIC and EPILOG:30 day Events(D,MI
24、,uTVR),Abciximab in PCI:Complex Lesions,p=.001,p=.001,p=.001,p=.001,p=.078,p=.001,p=.001,p=.001,JACC 1998;32:1619-23,%,EPISTENT Abciximab for Complex Lesions,30 day D,MI,uTVR,p=0.17,p0.001,Lancet 1999;354:2019-24,2009年中国PCI治疗指南GPb/a受体拮抗剂推荐,小 结,血小板在ACS发病中起重要作用抗血小板治疗是ACS的关键治疗之一GPb/a拮抗剂尤其适宜于中高危行介入治疗的ACS患者三重抗血小板治疗在ACS伴TNI升高者中尤为重要,谢 谢！,
