氯吡格雷与血小板反应

1 CLEARPLATELETS ClopidogrelLoadingwithEptifibatidetoArresttheReactivityofPlatelets 2 Introduction Wehavepreviouslyreportedasignificantincidenceofclopidogrelresistanceinpatientspost electivecoronarystentingtreatedwithastandard300 mgloadingdose1 31 at24hours Patientswithclopidogrelresistance highpost stentplateletreactivitymaybeatgreatestriskofSATandischemicevents2 4Relationofperi proceduralplateletreactivitytomyocardialnecrosishasneverbeenprospectivelystudiedThesedatasuggestthat300mgclopidogrel 75mgqddoesnotprovidesufficientinhibitioninsomepatientsundergoingelectivecoronarystenting 1 Gurbeletal Circulation 2003 107 2908 2 Mulleretal ThrombHaemost 2003 89 783 3 Barraganetal CatheterCardiovascInterv 2003 59 295 4 Matetzkyetal Circulation 2004 109 3171 3 Introduction cont d Mechanismsofclopidogrelnonresponse resistanceareincompletelydefined Studyof30pts n 10forticlodipine n 10forclopidogrel300mg n 10forclopidogrel600mg suggestedbetterinhibitionwith600mgat4hoursbutnodifferenceat24hourswith600 mgdose1 1 Mulleretal Heart 2001 85 92 4 Introduction cont d Alargeprospectivepharmacodynamicstudyofclopidogrel300mgvs600mgisnotavailableTheeffectofaddingeptifibatidetotheseregimensisunknownISARREACTsuggestednobenefitofaddingabciximabtopatientsloadedwith600mgclopidogrel1Patientsallpretreatedfor 2hours median7 4hours RiskofbleedingwithCABGinpatientsonclopidogreltherapy2Low riskgroup 1 Kastratietal NEnglJMed 2004 350 232 2 Hongoetal JAmCollCardiol 2002 40 231 5 ObjectivesofCLEARPLATELETSTrial Compareplateletreactivityfollowing4treatmentsinlow tomoderate riskpatientsundergoingelectivestentingWithoutpretreatment CRUSADE coronaryanatomyunknownpriortoprocedureDOSING600mgClopidogrel600mgClopidogrel eptifibatide300mgClopidogrel300mgClopidogrel eptifibatideAnalyzetherelationofplateletreactivitytopostproceduralmyocardialnecrosisAnalyzetherelationofplateletreactivitytopostproceduralinflammation Gurbeletal Circulation 2005 111 1153 6 Methods ConsecutivepatientsundergoingelectivecoronarystentingExclusioncriteriaChestpain1 5 Platelets4 0mg dLThienopyridineorGPIIb IIIause ElevatedcardiacmarkersCVA 3moVisiblethrombusHct 30 Bleedingdiathesis Gurbeletal Circulation 2005 111 1153 7 Clopidogrel300mg n 60 Clopidogrel600mg n 60 Eptifibatide n 30 Eptifibatide n 30 Eptifibatide n 30 Eptifibatide n 30 HeparinperESPRITdosingClopidogrel75mgqdASA325mgqd Methods cont d Treatmentregimens 2 2factorialstudy Gurbeletal Circulation 2005 111 1153 8 Results Demographics CAD coronaryarterydisease MI myocardialinfarction Gurbeletal Circulation 2005 111 1153 9 Results Demographics cont d Gurbeletal Circulation 2005 111 1153 10 Results AngiographicData Gurbeletal Circulation 2005 111 1153 11 Results ClinicalOutcomes 24hours TIMIcriteria Gurbeletal Circulation 2005 111 1153 12 RESULTS PLATELETREACTIVITY P 0 001forC300 EandC600 EvsC300aloneandC600alone P 0 001forC600alonevsC300alone P 0 01forC600alonevsC300alone Gurbeletal Circulation 2005 111 1153 RelativeInhibition 13 Results PlateletReactivity Clopidogrel300mgClopidogrel300mg eptifibatideClopidogrel600mgClopidogrel600mg eptifibatide 5 MADP P 0 001forC300 EandC600 EvsC300aloneandC600alone P 0 001forC600alonevsC300alone Gurbeletal Circulation 2005 111 1153 14 Results PlateletReactivity cont d 0 09 20 MADP 05 Hours Relativeinhibition Clopidogrel300mgClopidogrel300mg eptifibatideClopidogrel600mgClopidogrel600mg eptifibatide P 0 001forC300 EandC600 EvsC300aloneandC600alone P 0 01forC600alonevsC300alone Gurbeletal Circulation 2005 111 1153 15 PositiveCells P 0 02vsbaseline P 0 03vsC600alone C600 EandC300 E Gurbeletal Circulation 2005 111 1153 Results StimulatedP Selectin 5uMADP 16 Results StimulatedP Selectin 5 MADP Positivecells 0 10 20 30 40 50 60 70 Baseline 18 24hpoststenting Clopidogrel300mg Clopidogrel600mg Clopidogrel300mg eptifibatide Clopidogrel600mg eptifibatide P 0 02vsbaseline P 0 03vsC600alone C600 EandC300 E Gurbeletal Circulation 2005 111 1153 17 RelationofPlateletReactivitytoNecrosisMarkerRelease 5 MADP P 0 001 P 0 15 P 0 001 Meanplateletreactivity CKMB 3 ULN CKMB 1 3 ULN CKMB normal Gurbeletal Circulation 2005 111 1153 18 NoMI MI 5 MADP InducedAggregation Meanplateletreactivity P 0 01 RelationofMeanPosttreatmentAggregationtoOccurrenceofMI n 120 NoMI MI 20 MADP InducedAggregation Meanplateletreactivity P 0 01 Gurbeletal Circulation 2005 111 1153 19 CKMB 1 3XULN Patients CKMB 3XULN P 0 05forC300 EandC600 EvsC300aloneandC600alone Gurbeletal Circulation 2005 111 1153 RELATIONOFPLATELETREACTIVITYTOMYOCARDIALNECROSIS 20 CKMB 1 3 ULN CKMB 3 ULN Patients RelationofPlateletReactivitytoMyocardialNecrosis 0 10 20 30 P 0 05forC300 EandC600 EvsC300aloneandC600alone Gurbeletal Circulation 2005 111 1153 21 Patients Troponin I ULN Myoglobin 2XULN P 0 08 P 0 04 P 0 006 P 0 09 Gurbeletal Circulation 2005 111 1153 EARLYCLINICALRELEVANCEOFPLATELETREACTIVITY MYOCARDIALINFARCTION 22 Troponin I ULN Myoglobin 2 ULN P 0 08 P 0 04 P 0 006 P 0 09 Patients EarlyClinicalRelevanceofPlateletReactivity MyocardialInfarction 0 10 20 30 40 50 Gurbeletal Circulation 2005 111 1153 0 0 23 Conclusions PlateletreactivitycorrelatesstronglywiththedevelopmentofperiproceduralmyocardialnecrosisinelectivestentingWhenclopidogrelpretreatmentisnotpossibleorwhenthedurationofpretreatmentisinadequate astrategyofeptifibatideadministrationshouldbeconsideredsinceitisassociatedwithsuperiorplateletinhibitionandlowermyocardialnecrosisthaneither300mgor600mgclopidogrelaloneIntheabsenceofeptifibatide astrategyofclopidogrel600mgclearlyprovid