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1、血小板GP IIb/IIIa受体拮抗剂临床应用新视点上海交通大学附属胸科医院心内科仇兴标IIb/IIIa受体拮抗剂的作用机制Pharmacologic Intervention in ThrombosisUFH=unfractionated heparin.LMWH=low-molecular-weight heparinADP=adenosine diphosphate.TFPI=tissue factor pathway inhibitor Selwyn A.Am J Cardiol.2003;91:3H-11H.Coagulation cascadePlateletsLMWHThieno
2、pyridinesGP IIb/IIIa inhibitorsThrombolyticsLMWHUFHLMWHUFHDirect thrombininhibitorsTissue factorFactor XaProthrombinThrombinPlateletsA2 vWF ADPActivated plateletsFibrinogen cross-linkingPlatelet aggregationAspirinFibrinogenFibrinFibrindegradationCollagenLeukocytesTFPIAnti-thrombinAnti-thrombinThromb
3、oxanePlasminThrombusPharmaHalf-lifeRenal Adj.DosageAbciximab(ReoPro)Fab portion ofchimeric monoclonalantibody30minsNo0.25 mcg/kg bolusfollowed by0.125 mcg/kg/min drip(max 10 mcg/min)forup to 12 hoursTirofiban(Aggrastat)Synthetic non-peptide1.8hrsYes0.4 mcg/kg/min for 30minutes followed by0.1 mcg/kg/
4、min dripfor 48-96 hours25 mcg/kg for 3minutes followed by0.15 mcg/kg/min dripfor up to 18 hoursEptifibatide(Integrilin)Cyclic heptapeptide2.5hrsYes180 mcg/kg bolus(x2)followed by 2.0mcg/kg/min drip for12-18 hoursGP IIb/IIIa InhibitorsIIb/IIIa受体拮抗剂在PCI患者中的应用Kong D,et al.Am J Cardiol.2003;92:651-655.P
5、lacebo BetterIIb/IIIa BetterTrialControlTreatmentN0.1110RESTORE1.1%0.9%12,940EPILOG1.2%0.9%4891RAPPORT1.3%1.0%5374CAPTURE1.3%1.0%6639EPIC1.7%1.5%20991.3%IMPACT I1.0%67891.2%IMPACT II0.9%10,799ESPRIT1.0%0.8%17,403ISAR-21.1%0.8%17,804ADMIRAL1.2%0.8%18,104EPISTENT1.1%0.8%15,3391.3%CADILLAC 0.9%20,186Od
6、ds Ratio and 95%CI0.73(0.55,0.96)P=0.024Meta-analysis of Survival with Platelet GP IIb/IIIa Antagonists for PCIFavors ControlFavors TreatmentYearCAPTURE1997RESTORE1998EPISTENT19991997CADILLAC-P2002ADMIRAL2001RAPPORT1998Petronio2002CADILLAC-S20020.010.1110100StudyERASER1999ISAR-22000EPICRisk Ratio an
7、d 95%CIRR 0.79Z=-2.272P=0.023EPILOG1999ESPRIT2002OverallTamburino2002N126521411603209910463004838910362254012792206415,651107Karvouni E,et al.J Am Coll Cardiol.2003;41:26-32.Intravenous GP IIb/IIIa Receptor Antagonists Reduce Mortality after PCIISAR-REACTp=NSp=NSp=NSp=NS0.3%3.8%4.0%0.6%0.3%3.7%4.0%0
8、.9%0%5%10%DeathMIDeath/MIUrg RevacPlaceboAbciximabISAR-REACT low-risk PCI-30 days outcomep=0.06p=0.03p=0.34p=0.641.6%10.5%11.5%1.2%1.1%8.1%8.6%1.0%0%5%10%DeathMIDeath/MIUrg RevacPlaceboAbciximabISAR-REACT 2 high-risk PCI-30 days outcomeIn patients undergoing elective PCI treated with UFH and,it is r
9、easonable to administer a GP IIb/IIIa inhibitor(abciximab,double-bolus eptifibatide,or high-bolus dose tirofiban).I IIa IIb III In patients undergoing elective PCI it might be reasonable to administer a GP IIb/IIIa inhibitor(abciximab,double-bolus eptifibatide,or high-bolus dose tirofiban).I IIa IIb
10、 IIIIIb/IIIa受体拮抗剂在NSTE-ACS患者中的应用STEMIClinical findingEKGSerum markersRisk assessmentNon-cardiacchest painStableanginaUANSTEMINegativePositiveST-T wave changesST elevationLowprobabilityMedium-high riskThrombolysisPrimary PCIAspirin+GP IIb/IIIa inhibitor clopidogrel+heparin/LMWH+anti-ischemic RxEarly
11、invasive RxDischargeNegativeDiagnostic rule out MI/ACS pathwaySTEMI NegativeAtypical painLow riskAspirin,heparin/low-molecular-weight heparin(LMWH)+clopidogrelAnti-ischemic Rx Early conservative therapyOngoing painDM=diabetes mellitus.Cannon,Braunwald.Heart Disease.2001.Rest pain,Post-MI,DM,Prior As
12、pirinExertional painThe Spectrum of ACSPRISM(3232)7.1%5.8%0.800.60-1.06PRISM-PLUS(1915)12.0%8.7%0.700.50-0.98 PARAGON-A(2282)11.7%(l)10.3%0.870.58-1.29(h)12.3%1.060.72-1.55PURSUIT(10,948)15.7%14.2%0.890.79-1.00 PARAGON-B(5225)11.4%10.6%0.920.77-1.09GUSTO-IV(7800)8.0%(24h)8.2%1.020.83-1.24 (48h)9.1%1
13、.150.94-1.39Odds RatioPlaceboIV GP IIb/IIIa95%CI*With/without heparin.Without heparin.(l)=low dose.(h)=high-dose.Adapted from:Boersma E,et al.Lancet.2002;359:189-198.Placebo BetterGP IIb/IIIa BetterOdds Ratio(95%CI)0.01.02.0Study(n)GP IIb/IIIa Inhibitors in UA/NSTEMI:Death or MI at 30 DaysBenefit of
14、 GP IIb/IIIa Blockade in ACSMeta-Analysis of Six Major Trials(31,402 Patients)All patients with ACSPatients with ACS,undergoing PCI within 5 daysBoersma E et al.Lancet 20020.50.60.71.1Anti GPIIb/IIIa better0.80.91.0Relative 30-Day Risk of Death and MIIIb/IIIa ACS Meta-analysisIIb/IIIa ACS 30-day Dea
15、th or MI Early PCIIIb/IIIa ACS 30-day Death or MI No Early PCIACUITY:Ischemic Composite EndpointEARLY-ACS studyACC/AHA 2012年UA/NSTEMI指南n预行PCI的中、高危UA/NSTEMI患者，与阿司匹林联合应用GPb/受体拮抗剂，开始于术前(I/B)或术中(I/A)nBivalirudin作为术中抗凝时可不用GPb/a受体拮抗剂n对于选择保守策略的UA/NSTEMI患者，可应用依替巴肽或替罗非班进行抗栓治疗(b/B)n预行PCI的高危UA/NSTEMI且非高出血风险患者，
16、与双联抗血小板药联合上游应用GPb/受体拮抗剂(b/B)n阿昔单抗不应当应用于不准备行PCI的患者（/A）n预行PCI的低危UA/NSTEMI患者或高出血风险患者，不推荐与双联抗血小板药联合上游应用GPb/受体拮抗剂(/B)In UA/NSTEMI patients (e.g.,elevated troponin level)and,it is useful to administer a GP IIb/IIIa inhibitor(abciximab,double-bolus eptifibatide,or high-bolus dose tirofiban)in patients treated with UFH.I IIa IIb III In UA/NSTEMI patients (e.g.,elevated troponin level)treated with UFH and adequately pretreated with clopidogrel,it is reasonable to administer a GP IIb/IIIa inhibitor(abcixi
