替格瑞洛ChampionPhoenixIII期臨床試驗(yàn)結(jié)果系列

替格瑞洛ChampionPhoenixIII期臨床試驗(yàn)結(jié)果系列第1頁/共40頁Dr.Bhatt–AdvisoryBoard:MedscapeCardiology;BoardofDirectors:BostonVAResearchInstitute,SocietyofChestPainCenters;Chair:AmericanHeartAssociationGetWithTheGuidelinesScienceSubcommittee;Honoraria:AmericanCollegeofCardiology(Editor,ClinicalTrials,Cardiosource),DukeClinicalResearchInstitute(clinicaltrialsteeringcommittees),SlackPublications(ChiefMedicalEditor,CardiologyTodayIntervention),WebMD(CMEsteeringcommittees);Other:SeniorAssociateEditor,JournalofInvasiveCardiology;ResearchGrants:Amarin,AstraZeneca,Bristol-MyersSquibb,Eisai,Ethicon,Medtronic,SanofiAventis,TheMedicinesCompany;UnfundedResearch:FlowCo,PLxPharma,Takeda.Thispresentationincludesoff-labeland/orinvestigationalusesofdrugs,includingclopidogrelandcangrelor.TheCHAMPIONPHOENIXtrialwasfundedbyTheMedicinesCompany.Disclosures第2頁/共40頁AntiplateletTherapyAntiplatelettherapyisacriticalpartofcontemporaryPCI.Intheeraofaspirinandunfractionatedheparin,intravenousglycoproteinIIb/IIIainhibitionsignificantlyreducedimportantperiproceduralischemicevents,butsignificantlyincreasedbleeding.ADPreceptorantagonismwithoralagentswasalsoshowntoreduceischemiceventsinPCIandespeciallyACS.However,availableoralagentsarelimitedbytheirrelativelylongdurationofactionandbioavailability,whichmightbealiability:ifgivenpriortocoronaryangiographyandurgentoremergentCABGisdeemednecessary,insituationswhereabsorptionmaybeproblematic,suchaswithrapidtimestoPCI,inpatientswhoareintubated,nauseated,withSTEMI,orshock.HarringtonRA,etal.PURSUIT.NEJM1998DesaiNandBhattDL.PeriproceduralAntiplateletTherapy.JACCIntervention2010第3頁/共40頁CangrelorCangrelorisanintravenousADPreceptorantagonistthatisrapidlyacting,potent,andreversible,withreturnofnormalplateletfunctionwithinanhour.CangrelorwasstudiedpreviouslyintwolargePhase3PCItrials,CHAMPIONPCIandCHAMPIONPLATFORM.Neitherstudymetitsprimaryendpoint,butthesecondaryendpointofstentthrombosisat48hourswassignificantlyreducedinCHAMPIONPLATFORMandinaprespecifiedpooledanalysisofthetwotrials.Therewasnoexcessinseverebleeding.ThepotentialefficacysignalpromptedustolaunchtheCHAMPIONPHOENIXtrial.HarringtonRA,etal.CHAMPIONPCI.NEJM2009BhattDL,etal.CHAMPIONPLATFORM.NEJM2009WhiteHD,etal.Meta-AnalysisofCHAMPIONPCIandPLATFORM.AHJ2012第4頁/共40頁CHAMPIONPHOENIXExecutiveCommitteeDeepakL.Bhatt,M.D.,M.P.H.(Co-PrincipalInvestigator)

VABostonHealthcareSystem,BrighamandWomen'sHospital,andHarvardMedicalSchoolBoston,MARobertA.Harrington,M.D.(Co-PrincipalInvestigator)

DepartmentofMedicine,StanfordUniversity,Stanford,CAC.MichaelGibson,M.S.,M.D. BethIsraelDeaconessMedicalCenter,DivisionofCardiology,Boston,MAChristianW.Hamm,M.D.

KerckhoffHeartandThoraxCenter,BadNauheim,GermanyKennethW.Mahaffey,M.D.

DukeClinicalResearchInstitute,Durham,NCMatthewJ.Price,M.D. ScrippsClinicandScrippsTranslationalScienceInstitute,LaJolla,CAPh.GabrielSteg,M.D. INSERMU-698,UniversitéParis-Diderot,andH?pitalBichat,Assistance-Publique-H?pitauxdeParis,Paris,FranceGreggW.Stone,M.D.

ColumbiaUniversityMedicalCenterandtheCardiovascularResearchFoundation,NewYork,NYHarveyD.White,D.Sc.

AucklandCityHospital,Auckland,NewZealand第5頁/共40頁CHAMPIONPHOENIXDSMBFransVandeWerf,M.D.(Chair)

UniversitairZiekenhuisGasthuisberg,BelgiumDavidP.Faxon,M.D.

Brigham&Women’sHospital,Dept.ofMedicine,Boston,MAE.MagnusOhman,M.D.

DukeUniversityMedicalCenter,Durham,NCFreekW.A.Verheugt,M.D.

HeartcenterUniversityMedicalCenter,AmsterdamW.DouglasWeaver,M.D.

HenryFordHospital,Detroit,MIJanG.P.Tijssen,Ph.D.(Statistician)

DepartmentofCardiology,AcademicMedicalCenter-UniversityofAmsterdam,TheNetherlands第6頁/共40頁CHAMPIONPHOENIXCECDukeClinicalResearchInstituteREVIEWERSPhase1LucianaAmaganijan

BrazilMoniqueAndersonNC AkshayBagaiNCRobertW.HarrisonNCPedroG.MelodeBarrosESilvaBrazilPhase2J.MatthewBrennanNCRenatoD.Lopes

NCChiaraMelloniNCPierluigiTricociNCLEADERSHIPKennethW.Mahaffey(Chair)SergioLeonardi(co-Chair)DianneGallup(LeadStatistician)MatthewD.Wilson(ProjectLeader)OPERATIONSStaceyMangum(Coordinator)LindaDowd(LeadCDA)DimitriosStournaras(LeadCDS)SachinVyas(LeadCTA)第7頁/共40頁CHAMPIONPHOENIXAngiographicCoreLabCardiovascularResearchFoundationMariaAlfonsoAntoinetteAllenGerardCondittRosaDeJesusChampikaDjurkovicSharwatJahanGregKaluzaElenaKonovalovaMitchellLustreKatharineLymberisDuvalMichelSofiaPapamitrouNicolettaPavloviciKharyPerrySairaPunjwaniConnieQiuRaquelSanchezEliasSanidasShawnaleeVassellDoueyWrightReviewersandDataEntryStaffLeadershipPhilippeGénéreux

(Director)SorinBrener LauraLasalle第8頁/共40頁12Countries│153SitesUSAPolandGermanyAustriaThailandRussiaGeorgiaBulgariaBrazilCzechRepublicUSAPolandGermanyNewZealandAustriaItalyThailandRussiaGeorgiaBulgariaBrazilCHAMPIONPHOENIX–AGlobalTrial第9頁/共40頁CHAMPIONPHOENIXStudyDesignRandomized,double-blind,double-dummy,superiorityPrimaryefficacyendpoint:Death/MI/IDR/STat48hoursAdjustedfor600mgversus300mgclopidogreluseModifiedIntent-to-Treat(MITT)analysis(patientsactuallygotstudydrugandPCI)Keysecondaryendpoint:StentThrombosisat48hoursEfficacyendpointsalsoexaminedat30daysPrimarysafetyendpoint:GUSTOSevereBleedingat48hoursHarringtonRA,etal.CHAMPIONPCI.NEJM2009BhattDL,etal.CHAMPIONPLATFORM.NEJM2009WhiteHD,etal.Meta-AnalysisofCHAMPIONPCIandPLATFORM.AHJ2012第10頁/共40頁CHAMPIONPHOENIXStudyDesign12to4hours0Cangrelor2bolus&infusion(30ug/kg;4ug/kg/min)Clopidogrel600mgoralCHAMPIONPHOENIXN=10,900MITTSA/NSTE-ACS/STEMIPatientsrequiringPCI1P2Y12inhibitorna?veORPlacebo3oral(rightbeforePCIorrightafter,perphysician)Placebo2bolus&infusionPlacebooralPCI~30’ORClopidogrel3(600mgor300mgoral,perphysician)1RandomizationoccurredoncesuitabilityforPCIwasconfirmedeitherbyangiographyorSTEMIdiagnosis.Doubleblindstudymedicationwasadministeredassoonaspossiblefollowingrandomization.2StudydrugInfusion(cangrelorormatchingplacebo)wascontinuedfor2-4hoursatthediscretionofthetreatingphysician.Attheendoftheinfusionpatientsreceivedaloadingdoseofclopidogrelormatchingplaceboandweretransitionedtomaintenanceclopidogreltherapy.3Clopidogrelloadingdose(ormatchingplacebo)wasadministeredasdirectedbytheinvestigator.Atthetimeofpatientrandomization,aclopidogrelloadingdoseof600mgor300mgwasspecifiedbytheinvestigator.MITT=modifiedintent-to-treat;NSTE-ACS=non-ST-elevationacutecoronarysyndrome;PCI=percutaneouscoronaryintervention;SA=stableangina;STEMI=ST-elevationMI.Rand第11頁/共40頁Demographics,MITT

Cangrelor(N=5472)Clopidogrel(N=5470)Age,years6464Female28%27%Diabetesmellitus28%28%PatientType

Stableangina57%55%NSTE-ACS25%26%STEMI18%19%LoadingDose

300mgclopidogrel26%26%600mgclopidogrel74%74%Region

UnitedStates37%37%Othercountries63%63%第12頁/共40頁P(yáng)rimaryEfficacyOutcomesat48Hours,MITT

Cangrelor

(N=5472)Clopidogrel(N=5470)OR(95%CI)P-valuePrimaryAnalysisAdjusted1

Death/MI/IDR/ST

257/5470(4.7%)322/5469(5.9%)0.78(0.66,0.93)0.0051.Thelogisticmodelwasadjustedforbaselinestatusandclopidogreldose.Pvalueof0.006shownontheKMcurveislogrankpvalue.SecondaryEfficacyOutcomesat48Hours,MITTStentthrombosis(key

secondaryendpoint)46/5470(0.8%)74/5469(1.4%)0.62(0.43,0.90)0.01MI207/5470(3.8)255/5469(4.7)0.80(0.67,0.97)0.02Q-waveMI11/5470(0.2)18/5469(0.3)0.61(0.29,1.29)0.19IDR28/5470(0.5)38/5469(0.7)0.74(0.45,1.20)0.22Death18/5470(0.3)18/5469(0.3)1.00(0.52,1.92)>0.99CVDeath18/5470(0.3)18/5469(0.3)1.00(0.52,1.92)>0.99BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第13頁/共40頁

Death/MI/IDR/StentThrombosiswithin48HoursPatientatRiskHoursfromRandomizationCangrelor:547252335229522552235221522052175213Clopidogrel:547051625159515551525151515151475147cangrelorclopidogrel5.9%4.7%LogRankPValue=0.006EventRate(%)BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第14頁/共40頁cangrelorclopidogrelLogRankPValue=0.01PatientatRiskHoursfromRandomizationCangrelor:547254265421541954195418541754165414Clopidogrel:5470539253895388538653855385538353831.4%0.8%EventRate(%)StentThrombosiswithin48HoursBhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第15頁/共40頁EfficacyOutcomesat30Days,MITT

Cangrelor(N=5472)Clopidogrel(N=5470)OR(95%CI)PValueDeath/MI/IDR/ST(primaryendpoint,adjusted)326/5462(6.0%)380/5457(7.0%)0.85(0.73,0.99)0.03Stentthrombosis71/5462(1.3%)104/5457(1.9%)0.68(0.50,0.92)0.01MI225/5462(4.1%)272/5457(5.0%)0.82(0.68,0.98)0.03

Q-waveMI14/5462(0.3%)22/5457(0.4%)0.63(0.32,1.24)0.18IDR56/5462(1.0%)66/5457(1.2%)0.85(0.59,1.21)0.36Death60/5462(1.1%)55/5457(1.0%)1.09(0.76,1.58)0.64CVDeath48/5462(0.9%)46/5457(0.8%)1.04(0.69,1.57)0.84BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第16頁/共40頁OR[95%CI]P[Int]Overall

0.79(0.67,0.93)Age≥750.71(0.50,1.02)0.55Age<750.81(0.67,0.98)Male0.84(0.69,1.03)0.23Female0.67(0.50,0.92)Ethnicity:White0.80(0.67,0.95)0.72Ethnicity:Non-white0.70(0.35,1.41)UnitedStates0.70(0.53,0.92)0.26OtherCountries0.85(0.69,1.05)StableAngina0.78(0.63,0.95)0.98NSTE-ACS0.80(0.55,1.17)STEMI0.75(0.46,1.25)Weight>=600.79(0.66,0.94)0.89Weight<600.75(0.39,1.45)BiomarkerPositive0.90(0.64,1.27)0.35BiomarkerNegative0.75(0.61,0.91)DiabeticNo0.74(0.61,0.90)0.26DiabeticYes0.92(0.67,1.27)Insulin-DependentDiabetes:Yes0.74(0.42,1.31)0.82Insulin-DependentDiabetes:No0.79(0.66,0.94)PriorMI0.68(0.47,0.97)0.30NoPriorMI0.84(0.69,1.02)5.01.00.2Subgroups:Death/MI/IDR/STat48HoursCangrelorBetterClopidogrelBetter第17頁/共40頁OR[95%CI]P[Int]PriorTIA/Stroke0.78(0.37,1.63)0.97NoPriorTIA/Stroke0.79(0.66,0.94)HistoryofPAD0.36(0.21,0.63)0.003NoHistoryofPAD0.86(0.72,1.03)HistoryofCHF0.73(0.45,1.20)0.74NoHistoryofCHF0.80(0.67,0.96)Clopidogrel300mg0.84(0.62,1.14)0.62Clopidogrel600mg0.77(0.63,0.94)Bivalirudinonly0.69(0.47,1.01)0.51Heparinonly0.80(0.65,0.98)Femoral0.79(0.65,0.96)0.83Radial0.76(0.54,1.06)#vessels=10.80(0.66,0.97)0.51#vessels≥20.70(0.49,0.99)Drug-ElutingStent0.80(0.64,1.01)0.79Bare-MetalStent0.77(0.60,0.99)Aspirin≤100mg0.80(0.63,1.00)0.49Aspirin>100mg0.70(0.52,0.94)ClopidogrelLoadbeforePCIStart0.80(0.64,0.98)0.99ClopidogrelLoadafterPCIStart0.79(0.59,1.06)Cangrelorinfusion≤129minutes0.85(0.68,1.07)0.31Cangrelorinfusion>129minutes0.72(0.56,0.92)Subgroups:Death/MI/IDR/STat48Hours(continued)5.01.00.2CangrelorBetterClopidogrelBetter第18頁/共40頁Non-CABGBleedingat48Hours,SafetyBleedingScaleCangrelor(N=5529)Clopidogrel(N=5527)OR(95%CI)PValueGUSTOSevere9(0.16%)6(0.11%)1.50(0.53,4.22)0.44GUSTOModerate22(0.4%)13(0.2%)1.69(0.85,3.37)0.13GUSTOSevere+Moderate31(0.6%)

19(0.3%)1.63(0.92,2.90)0.09TIMIMajor5(0.1%)5(0.1%)1.00(0.29,3.45)>0.999TIMIMinor9(0.2%)3(0.1%)3.00(0.81,11.10)0.08TIMIMajor+Minor14(0.3%)8(0.1%)1.75(0.73,4.18)0.2AnyBloodTransfusion25(0.5%)16(0.3%)1.56(0.83,2.93)0.16ACUITYMajor235(4.3%)139(2.5%)1.72(1.39,2.13)<0.001ACUITYw/outhematoma42(0.8%)

26(0.5%)1.62(0.99,2.64)0.05BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第19頁/共40頁OR[95%CI]P[Int]Overall1.63(0.92,2.90)Age≥751.07(0.45,2.53)0.21Age<752.24(1.02,4.93)Male0.93(0.41,2.12)0.07Female2.75(1.16,6.51)Ethnicity:White1.86(0.97,3.56)0.40Ethnicity:Non-white1.02(0.29,3.56)UnitedStates1.34(0.56,3.18)0.55OtherCountries1.90(0.88,4.10)StableAngina1.45(0.59,3.56)0.93NSTE-ACS1.79(0.52,6.13)STEMI1.84(0.72,4.70)Weight>=601.52(0.80,2.86)0.71Weight<602.01(0.52,7.86)BiomarkerPositive1.51(0.64,3.53)0.79BiomarkerNegative1.76(0.81,3.82)DiabeticNo1.90(0.88,4.09)0.56DiabeticYes1.35(0.57,3.20)Insulin-DependentDiabetes:Yes3.56(0.40,32.00)0.45Insulin-DependentDiabetes:No1.52(0.83,2.76)PriorMI3.25(0.65,16.12)0.35NoPriorMI1.44(0.78,2.67)ClopidogrelBetterSubgroups:GUSTOSevere/ModerateBleeding,Safety5.01.00.2CangrelorBetter第20頁/共40頁Subgroups:GUSTOSevere/ModerateBleeding,Safety(continued)ClopidogrelBetter5.01.00.2CangrelorBetterOR[95%CI]P[Int]PriorTIA/Stroke0.92(0.13,6.55)0.54NoPriorTIA/Stroke1.72(0.94,3.13)HistoryofPADNA0.10NoHistoryofPAD1.55(0.84,2.87)HistoryofCHF2.13(0.39,11.70)0.85NoHistoryofCHF1.79(0.95,3.37)Clopidogrel300mg4.02(1.13,14.27)0.09Clopidogrel600mg1.19(0.61,2.31)Bivalirudinonly0.86(0.26,2.83)0.26Heparinonly1.89(0.91,3.93)Femoral1.68(0.90,3.11)0.81Radial1.37(0.31,6.11)#vessels=11.81(0.94,3.49)0.48#vessels≥21.12(0.34,3.68)Drug-ElutingStent1.26(0.57,2.77)0.35Bare-MetalStent2.17(0.93,5.03)Aspirin≤100mg1.58(0.52,4.85)0.93Aspirin>100mg1.49(0.74,3.03)ClopidogrelLoadbeforePCIStart1.24(0.58,2.66)0.25ClopidogrelLoadafterPCIStart2.53(0.98,6.54)Cangrelorinfusion≤129minutes1.71(0.81,3.59)0.85Cangrelorinfusion>129minutes1.52(0.62,3.73)第21頁/共40頁SummaryofTreatmentEmergent

AdverseEvents

AdverseEventCangrelor(N=5529)Clopidogrel(N=5527)PValuePatientswithatleastoneAE20.2%19.1%0.13PatientswithatleastoneAEcausingstudydrugdiscontinuation0.5%0.4%0.21Transientdyspnea1.2%0.3%<0.001BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第22頁/共40頁LimitationsAloadingdoseof600mghasbecomemorecommonthan300mgHowever,inthethreequartersofpatientswhoreceived600mg,thebenefitofcangrelorremainedstatisticallysignificantandwasnotattenuated.Itispossiblethebenefitswesawherewouldhavebeenattenuatedwithalongerdurationofpretreatment.Ofnote,theclopidogrelpretreatmentwasgiven“onthetable”asisconsistentwithmanypracticesaroundtheworldandinparticularintheUnitedStates.Importantly,prospectiverandomizedclinicaltrials,namelyCREDOandPRAGUE-8,didnotfindasignificantbenefitforclopidogrelpretreatment.Thebenefitsseenheremayalsohavebeenattenuatedhadprasugrelorticagrelorbeenusedinthecontrolarm.However,todate,thelargesttrialofprasugrelpretreatment,ACCOAST,wasterminatedbytheDSMBforlackofefficacyandexcessbleeding.Thus,oralpretreatment,whilebiologicallyappealingandintuitive,remainsunproveninprospectiverandomizedclinicaltrials.第23頁/共40頁ConclusionsInCHAMPIONPHOENIX,intravenousADPreceptorantagonismwithcangrelorsignificantly(p=0.005)reducedthecompositeofdeath,myocardialinfarction,ischemia-drivenrevascularization,orstentthrombosisat48hours,witha22%oddsreduction.Thekeysecondaryendpointofstentthrombosiswasalsosignificantlyreduced,witha38%oddsreduction.Thebenefitwassustainedthrough30days.Therewasnoexcessinseverebleedingortransfusions.IntravenouscangrelormaybeanattractiveoptionacrossthefullspectrumofPCI,includingstableangina,NSTEMI,andSTEMI.第24頁/共40頁ForFullDetails,PleaseGotowww.NEJM.orgBhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第25頁/共40頁THANKYOU!第26頁/共40頁BACKUPSLIDES第27頁/共40頁CangrelorDirectplateletP2Y12receptorantagonist

ATPanalogueMW=800DaltonsParenteraladministrationT1/2=3to6minutesOffset=60minutesNNNNNHSCF3OHOHOOPOOPPOOOClClOOOS4Na+AngiolilloDJ,SchneiderDJ,BhattDL,etal.Pharmacodynamiceffectsofcangrelorandclopidogrel:theplateletfunctionsubstudyfromthecangrelorversusstandardtherapytoachieveoptimalmanagementofplateletinhibition(CHAMPION)trials.JThrombThrombolysis2012;34:44-55.第28頁/共40頁CHAMPIONPCI|PLATFORMPCI|allcomersPCI|58%ACS|onclopidogrelallowed|clopidogrel600mgadministeredatthestartofPCIinthecontrolarmPLATFORM|allcomersPCI|65%ACS|clopidogrelna?ve

|clopidogrel600mgadministeredattheendofPCIinthecontrolarm

12hours0PCI~25’Cangrelor30g/kgthen4g/kg/minCangrelor30g/kgthen4g/kg/minClopidogrel600mgoralClopidogrel600mgoral

CHAMPIONPCIN=9000SA/UA/ACS/STEMIOnclopidogrelallowedCHAMPIONPLATFORMN=6400SA/UA/ACSNoclopidogrelallowedHarringtonRA,etal.NEJM2009BhattDL,etal.NEJM2009第29頁/共40頁48-HourEventsPLATFORMOR[95%CI]PvalueDeath/MI/IDR0.87(0.71,1.07)0.17Death/Q-MI/IDR0.55(0.33,0.93)0.02Death/Q-MI/ST0.38(0.20,0.72)0.003PCIDeath/MI/IDR1.05(0.89,1.24)0.57Death/Q-MI/IDR0.66(0.42,1.05)0.08Death/Q-MI/ST0.74(0.43,1.27)0.27POOLEDDeath/MI/IDR0.97(0.86,1.11)0.68Death/Q-MI/IDR0.61(0.43,0.86)0.005Death/Q-MI/ST0.55(0.36,0.83)0.004CangrelorBetter5.02.01.00.20.5ComparatorBetterSummaryofClinicalEfficacy1.BhattDL,LincoffAM,GibsonCM,etal.IntravenousplateletblockadewithcangrelorduringPCI.NEnglJMed2009;361:2330-41.2.HarringtonRA,StoneGW,McNultyS,etal.PlateletinhibitionwithcangrelorinpatientsundergoingPCI.NEnglJMed2009;361:2318-29.3.WhiteHD,ChewDP,DauermanHL,etal.AHJ2012.第30頁/共40頁CHAMPIONPHOENIXLessonsfromCHAMPIONPCI|PLATFORMTrialDesignImplementationPatientpopulationAllcomersPCIInclusionofpatientswithnormalcardiacmarkersatbaseline|est.65%trialpopulationP2Y12inhibitorna?vePatientsnotpre-treatedwithP2Y12inhibitorwithin7dayspriortoangiogramEndpointdefinitionsMIdefinition1UDMI|CentrallabtoassureconsistencyofCKMBmassassayglobally|angiographiccorelabtoconsistentlyassessevidenceofischemiaStentthrombosisdefinition2

ARCDefinitionincludes

occurrenceassociatedwithIDR|Death|MI|alsointra-proceduralstentthrombosismeasuredbyangiographiccorelab31.ThygesenK,AlpertJS,andWhiteHD,onbehalfoftheJointESC/ACCF/WHFTaskForcefortheRedefinitionofMyocardialInfarction.Universaldefinitionofmyocardialinfarction.EurHeartJ.2007;28:2525-2538.

2.CutlipDE,WindeckerS,MehranR,etal.Clinicalendpointsincoronarystenttrials:acaseforstandardizeddefinitions.Circulation2007;115:2344-2351.3.BrenerSJ,CristeaE,KirtaneAJ,etal.Intra-ProceduralStentThrombosis.JAmCollCardiolIntv

2013;6:36–43.第31頁/共40頁UniversalDefinitionofMI

ThygesenK,AlpertJS,andWhiteHD,onbehalfoftheJointESC/ACCF/WHFTaskForcefortheRedefinitionofMyocardialInfarction.Universaldefinitionofmyocardialinfarction.EurHeartJ.2007;28:2525-2538.BetterdiscriminationofMIwithconsiderationofmultiplecriteriaCKMBelevations|ischemicsymptoms|

angiographicevidence|ECGchangesDiagnosisofMIfromvariousperspectivesType1|spontaneousMIrelatedtoischemiaType2|MIsecondarytoischemia|changeinO2demand/supplyType3|suddenunexpectedcardiacdeathType4|associatedwithcoronaryangioplasty|stents

Type4a|MIassociatedwithPCIType4b|MIassociatedwithStentThrombosisType5|MIassociatedwithCABG第32頁/共40頁DefinitionofSTAngiographicEvidence:ARCST(AcademicResearchConsortium)1Acute(<24hourspost-procedure)Subacutestentthrombosis(>24hoursand≤30days)DefinitefromprobablestentthrombosisAdjudicatedbytheCECIPST(Intra-proceduralstentthrombosis)NeworworseningthrombusrelatedtothestentorAbruptclosuredueto

thrombosis1.CutlipDE,WindeckerS,MehranR,etal.Clinicalendpointsincoronarystenttrials:acaseforstandardizeddefinitions.Circulation2007;115(17):2344-2351.第33頁/共40頁SampleSizeEstimationEventrateof5.1%intheclopidogrelarmand3.9%inthecangrelorarm(24.5%reductioninoddsratio)N=10,900(powerof85%todetectthisdifferenceattheonesidedsignificancelevelof0.025)BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013at第34頁/共40頁MDCOClinical+DataOperationsLEADERSHIPJennaBisch(ProjectLead)TracySurvill(DataLead)Tiepu

Liu(Statistician)SteveElkin(Programming)MarkusDietrich(Medical)PROJECTMANAGEMENTDeniseEvansTaraRichardsonNitaWhyteIN-HOUSEOPERATIONSDanielBoisvertKathieVolcyLaurenEnsleyMariluMontalvoDATAMANAGEMENTCindyCleggKalpanaPullakhandamMichelleArthurGretchenCleggPamHoffmanKathleenTencerJuliaBaughSowersLucyWangunyuLindaConnollyCind