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1、那些病人能从GPIIb/IIIaInhibitors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,CharacteristicsofGPIIb/IIIaInhibitorsGPIIb/IIIaInhibitorsinACSGPIIb/IIIaInhibitorsinSTEMIGPIIb/IIIaInhibitorsandPCI,一、CharacteristicsofGPIIb/IIIaInhibitors,WhiteHD.AmJCardiol.1997;80(4A):2B-10B.,GPIIb/IIIa受体拮抗剂作用机制,Restingplatelet,Pl
2、aqueruptureandplateletadhesion,Plateletactivation,Preventionofplateletaggregation,GPIIb/IIIaexpression,Fibrinogen,GPIIb/IIIainhibitor,vWF,vWF,vWF,Agonists,released,VesselWall,三种静脉GPb/a受体抑制剂的比较,二、GPIIb/IIIaInhibitorsinACS,GPIIb/IIIaInhibitorsinACS,ThePrism-PlusInvestigators.NEJM1998;338:1488-97,-Deat
3、horMIat30days-,OR0.700.51,0.96P=0.03,ThePURSUITInvestigators.NEJM1998;339:436-43,OR0.900.75,0.98P=0.04,16.7%,15.6%,14.5%,11.6%,0%,5%,10%,15%,20%,Heparin,Eptifibatide+Heparin,ImpactofEarlyPCIon30DayDeath/MI,10.2%,10.1%,7.8%,5.9%,0%,5%,10%,15%,Heparin,Tirofiban+Heparin,PRISMPlus,PURSUIT,DM,Non-DM,5%,1
4、0%,6.2%,Placebo,GPIIb/IIIaInhibitor,4.6%,P=0.007,3.0%,3.0%,P=NS,GPIIb/IIIaInhibitorsinACS30-DaymortalityresultsofaMeta-analysis*,Circulation2001;104:2767-71,*PRISM,PRISM-PLUS,PARAGONA104:2767-2771,30-DayMortalityofaMeta-analysis*,n=1,279,n=5,179,*PRISM,PRISM-PLUS,PARAGONA357:1915-24,P=0.664,P=0.235,
5、P=0.190,GUSTO-IV30-Dayoutcomes,Lancet2001;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,Abciximab24h,Abciximab48h,Death,MI,*p0.05,vsplacebo,*,*,*,*,100,000perL,50,000perL,GUSTO-IVsafetyoutcomes,Lancet2001;357:1915-24,*,BenefitsofGPIIb/IIIaInhibitorsbyTr
6、oponinStatusinClinicalTrials,Circulation2001;103:2891-96,TnT-Negative,TnT-Positive,PARAGON-B,PRISM,CAPTURE,Combined,0.125,1,2,0.5,0.125,1,2,0.5,GPIIb/IIIaBetter,GPIIb/IIIaWorse,GPIIb/IIIaBetter,GPIIb/IIIaWorse,ISAR-REACT2Death,MI,orurgentTVRinSubsetsWithandWithoutElevatedTroponinLevels(0.03g/L),0,5,
7、10,15,20,25,30,DaysAfterRandomization,PlaceboGroup(N=1010)AbciximabGroup(N=1012),Troponin0.03g/LLog-Rankp=0.02,Troponin0.03g/LLog-Rankp=0.98,JAMA2006;295:1531-38,%,早期应用有效降低住院死亡率NRMI注册研究,NRMI-NSTEMIRiskScore,N=60770NSTEMI患者,住院死亡率%,NRMI=NationalRegistryofMyocardialInfarction.PetersonE,etal.JAmCollCard
8、iol.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/IIIaVS安慰剂,JAMA.2000;284:1549-1558,2009年中国PCI治疗指南GPb/a受体拮抗剂推荐,三、GPIIb/IIIaInhibitorsinSTEMI,%,GPIIb/IIIaInhibitorsinSTEMI,AbciximabandPCIinSTEMITrials30DayEndpoint(D,Re-MI,u-TVR),p=0.023,p0.05,p=0.005,PTCAN=483,StentN=401
9、,StentN=301,PTCAorStentN=2082,StentN=400,p=0.038,p=0.01,RAPPORTAbciximabinprimaryPTCAforSTEMI,9.9%,3.3%,5.0%,2.1%,5.4%,1.2%,P=0.003,p=0.098,P=0.01,Circulation1998;98;734-741,7-dayOutcome,RAPPORT,11.2%,5.8%,5.8%,4.6%,6.6%,1.7%,P=0.03,P=0.52,P=0.006,30Dayfollow-up,Circulation.1998;98:734-741,28.1%,28.
10、2%,17.8%,11.6%,11.2%,8.7%,P=0.9,P=0.048,P=0.36,Circulation.1998;98:734-741,RAPPORT6monthfollow-up,PrimaryPTCA(n=518),MultiLinkstent+Abciximab(n=524),PrimaryPTCA+Abciximab(n=528),MultiLinkstent(n=512),randomization,CADILLAC,AMI12h,cardiogenicshockexcludedN=208276centersinN.A.S.A.andEurope,NEnglJMed20
11、02;346:957-966,CADILLACKaplan-MeierEstimatesoftheClinicalOutcomesat30Daysand6Months,NEnglJMed2002;346:957-966,CADILLAC30dayacutethrombosis,P=0.05,P=0.03,NEnglJMed2002;346:957-966,CADILLACthrombocytopeniaandbleedingevnts,PTCAPTCA/AbcxStentStent/AbcxpBleeding-sever0.6%0.2%0.4%0.8%0.58-moderate2.5%2.3%
12、4.3%2.5%0.18-intrcranial0%0%0%0.2%0.99thrombocytopenia1.4%4.0%2.6%4.0%0.02Blood-productintrafusion3.7%5.1%4.1%5.0%0.62,NEnglJMed2002;346:957-966,ADMIRAL研究,300患者，AMI12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,Circulation2001;103:2328-2335,PRISM-PLUSAngiographicSubstudy:TirofibanIncreasedPerfu
13、sionStatus,P=0.002fortrendbyproportionaloddsmodel,ZhaoX-Q,etal.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数,2
14、009年中国PCI治疗指南GPb/a受体拮抗剂推荐,四、GPIIb/IIIaInhibitorsandPCI,Placebobetter,GPIbetter,0,0.5,1,1.5,2,0.62(0.55,0.71)p0.000000001,16,770,8.8%,5.6%,GPIIb/IIIaInhibitorsandPCImeta-Analysis,30-dayMI/death,EPISTENT1-yearresultsindiabetes,*P0.11,*P0.005,*P0.022,*P0.035,P0.440,P0.290,P0.389,P0.546,stent+placeboVSangiolpasy+abciximab*stent+placeboVSstent+abciximab,Lancet1999;354:2019-24,EPISTENT,Lancet1999;354:2019-24,1-yearmortality,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
