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CHAMPIONPHOENIXDeepakL.Bhatt,MD,MPH,GreggW.Stone,MD,KennethW.DeepakL.Bhatt,MD,MPH,GreggW.Stone,MD,KennethW.Mahaffey,MD,C.MichaelGibson,MS,MD,Ph.GabrielSteg,MD,Mahaffey,MD,C.MichaelGibson,MS,MD,Ph.GabrielSteg,MD,ChristianHamm,MD,MatthewPrice,MD,SergioLeonardi,MD,ChristianHamm,MD,MatthewPrice,MD,SergioLeonardi,MD,DianneGallup,MS,MeredithTodd,SimonaSkerjanec,PharmD,DianneGallup,MS,MeredithTodd,SimonaSkerjanec,PharmD,HarveyD.White,DSc,andRobertA.Harrington,MD,onbehalfofHarveyD.White,DSc,andRobertA.Harrington,MD,onbehalfoftheCHAMPIONPHOENIXInvestigatorstheCHAMPIONPHOENIXInvestigatorsCHAMPION PHOENIXDeepak L.BhatDr.BhattAdvisoryBoard: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.DisclosuresDr.Bhatt Advisory Board:MeAntiplateletTherapyAntiplatelettherapyisacriticalpartofcontemporaryPCI.Intheeraofaspirinandunfractionatedheparin,intravenousglycoproteinIIb/IIIainhibitionsignificantlyreducedimportantperiproceduralischemicevents,butsignificantlyincreasedbleeding.ADPreceptorantagonismwithoralagentswasalsoshowntoreduceischemiceventsinPCIandespeciallyACS.However,availableoralagentsarelimitedbytheirrelativelylongdurationofactionandbioavailability,whichmightbealiability:ifgivenpriortocoronaryangiographyandurgentoremergentCABGisdeemednecessary,insituationswhereabsorptionmaybeproblematic,suchaswithrapidtimestoPCI,inpatientswhoareintubated,nauseated,withSTEMI,orshock.HarringtonRA,etal.PURSUIT.NEJM1998DesaiNandBhattDL.PeriproceduralAntiplateletTherapy.JACCIntervention2010Antiplatelet TherapyAntiplatelCangrelorCangrelorisanintravenousADPreceptorantagonistthatisrapidlyacting,potent,andreversible,withreturnofnormalplateletfunctionwithinanhour.CangrelorwasstudiedpreviouslyintwolargePhase3PCItrials,CHAMPIONPCIandCHAMPIONPLATFORM.Neitherstudymetitsprimaryendpoint,butthesecondaryendpointofstentthrombosisat48hourswassignificantlyreducedinCHAMPIONPLATFORMandinaprespecifiedpooledanalysisofthetwotrials.Therewasnoexcessinseverebleeding.ThepotentialefficacysignalpromptedustolaunchtheCHAMPIONPHOENIXtrial.HarringtonRA,etal.CHAMPIONPCI.NEJM2009BhattDL,etal.CHAMPIONPLATFORM.NEJM2009WhiteHD,etal.Meta-AnalysisofCHAMPIONPCIandPLATFORM.AHJ2012CangrelorCangrelor is an intraCHAMPIONPHOENIXExecutiveCommitteeDeepakL.Bhatt,M.D.,M.P.H.(Co-PrincipalInvestigator)VABostonHealthcareSystem,BrighamandWomensHospital,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,UniversitParis-Diderot,andHpitalBichat,Assistance-Publique-HpitauxdeParis,Paris,FranceGreggW.Stone,M.D.ColumbiaUniversityMedicalCenterandtheCardiovascularResearchFoundation,NewYork,NYHarveyD.White,D.Sc.AucklandCityHospital,Auckland,NewZealandCHAMPION PHOENIX Executive ComCHAMPIONPHOENIXDSMBFransVandeWerf,M.D.(Chair)UniversitairZiekenhuisGasthuisberg,BelgiumDavidP.Faxon,M.D.Brigham&WomensHospital,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,TheNetherlandsCHAMPION PHOENIX DSMBFrans VanCHAMPIONPHOENIXCECDuke Clinical Research InstituteREVIEWERSPhase1LucianaAmaganijanBrazilMoniqueAndersonNCAkshayBagaiNCRobertW.HarrisonNCPedroG.MelodeBarrosESilvaBrazilPhase2J.MatthewBrennanNCRenatoD.LopesNCChiaraMelloniNCPierluigiTricociNCLEADERSHIPKennethW.Mahaffey(Chair)SergioLeonardi(co-Chair)DianneGallup(LeadStatistician)MatthewD.Wilson(ProjectLeader)OPERATIONSStaceyMangum(Coordinator)LindaDowd(LeadCDA)DimitriosStournaras(LeadCDS)SachinVyas(LeadCTA)CHAMPION PHOENIX CECDuke CliniCHAMPIONPHOENIXAngiographicCoreLabCardiovascular Research FoundationMariaAlfonsoAntoinetteAllenGerardCondittRosaDeJesusChampikaDjurkovicSharwatJahanGregKaluzaElenaKonovalovaMitchellLustreKatharineLymberisDuvalMichelSofiaPapamitrouNicolettaPavloviciKharyPerrySairaPunjwaniConnieQiuRaquelSanchezEliasSanidasShawnaleeVassellDoueyWrightReviewers and Data Entry StaffLeadershipPhilippeGnreux(Director)SorinBrenerLauraLasalleCHAMPION PHOENIX Angiographic 12Countries153SitesUSAPolandGermanyAustriaThailandRussiaGeorgiaBulgariaBrazilCzechRepublicUSAPolandGermanyNewZealandAustriaItalyThailandRussiaGeorgiaBulgariaBrazilCHAMPIONPHOENIXAGlobalTrial12 Countries 153 SitesUSAPolaCHAMPIONPHOENIXStudyDesignRandomized,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.AHJ2012CHAMPION PHOENIX Study DesignRCHAMPIONPHOENIXStudyDesign12to4hours0Cangrelor2bolus&infusion(30ug/kg;4ug/kg/min)Clopidogrel600mgoralCHAMPIONPHOENIXN=10,900MITTSA/NSTE-ACS/STEMIPatientsrequiringPCI1P2Y12inhibitornaveOR Placebo3oral(rightbeforePCIorrightafter,perphysician)Placebo2bolus&infusionPlacebooralPCI30OR Clopidogrel3(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.RandCHAMPION PHOENIX Study Design1Demographics,MITTCangrelor(N=5472)Clopidogrel(N=5470)Age,years6464Female28%27%Diabetesmellitus28%28%PatientTypeStableangina57%55%NSTE-ACS25%26%STEMI18%19%LoadingDose300mgclopidogrel26%26%600mgclopidogrel74%74%RegionUnitedStates37%37%Othercountries63%63%Demographics,MITTCangrelorClPrimaryEfficacyOutcomesat48Hours,MITTCangrelor(N=5472)Clopidogrel(N=5470)OR(95%CI)P-valuePrimaryAnalysisAdjusted1Death/MI/IDR/ST257/5470(4.7%)322/5469(5.9%)0.78(0.66,0.93)0.0051.Thelogisticmodelwasadjustedforbaselinestatusandclopidogreldose.Pvalueof0.006shownontheKMcurveislogrankpvalue.SecondaryEfficacyOutcomesat48Hours,MITTStentthrombosis(keysecondaryendpoint)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.NEJM2013atwww.nejm.orgPrimary Efficacy Outcomes at 4Death/MI/IDR/StentThrombosiswithin48HoursPatientatRiskHoursfromRandomizationCangrelor:547252335229522552235221522052175213Clopidogrel:547051625159515551525151515151475147cangrelorclopidogrel5.9%4.7%LogRankPValue=0.006EventRate(%)BhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgDeath/MI/IDR/Stent ThrombocangrelorclopidogrelLogRankPValue=0.01PatientatRiskHoursfromRandomizationCangrelor:547254265421541954195418541754165414Clopidogrel:5470539253895388538653855385538353831.4%0.8%EventRate(%)StentThrombosiswithin48HoursBhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgcangrelorclopidogrelLog Rank PEfficacyOutcomesat30Days,MITTCangrelor(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)0.03Q-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.NEJM2013atwww.nejm.orgEfficacy Outcomes at 30 Days,OR95%CIPIntOverall0.79(0.67,0.93)Age750.71(0.50,1.02)0.55Age=600.79(0.66,0.94)0.89Weight100mg0.70(0.52,0.94)ClopidogrelLoadbeforePCIStart0.80(0.64,0.98)0.99ClopidogrelLoadafterPCIStart0.79(0.59,1.06)Cangrelorinfusion129minutes0.85(0.68,1.07)0.31Cangrelorinfusion129minutes0.72(0.56,0.92)Subgroups:Death/MI/IDR/STat48Hours(continued)5.01.00.2CangrelorBetterClopidogrelBetterOR 95%CIP IntPrior TIA/StNon-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.NEJM2013atwww.nejm.orgNon-CABG Bleeding at 48 Hours,OR95%CIPIntOverall1.63(0.92,2.90)Age751.07(0.45,2.53)0.21Age=601.52(0.80,2.86)0.71Weight100mg1.49(0.74,3.03)ClopidogrelLoadbeforePCIStart1.24(0.58,2.66)0.25ClopidogrelLoadafterPCIStart2.53(0.98,6.54)Cangrelorinfusion129minutes1.71(0.81,3.59)0.85Cangrelorinfusion129minutes1.52(0.62,3.73)Subgroups:GUSTO Severe/ModeraSummaryofTreatmentEmergentAdverseEventsAdverseEventCangrelor(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.NEJM2013atwww.nejm.orgSummary of Treatment Emergent LimitationsAloadingdoseof600mghasbecomemorecommonthan300mgHowever,inthethreequartersofpatientswhoreceived600mg,thebenefitofcangrelorremainedstatisticallysignificantandwasnotattenuated.Itispossiblethebenefitswesawherewouldhavebeenattenuatedwithalongerdurationofpretreatment.Ofnote,theclopidogrelpretreatmentwasgiven“onthetable”asisconsistentwithmanypracticesaroundtheworldandinparticularintheUnitedStates.Importantly,prospectiverandomizedclinicaltrials,namelyCREDOandPRAGUE-8,didnotfindasignificantbenefitforclopidogrelpretreatment.Thebenefitsseenheremayalsohavebeenattenuatedhadprasugrelorticagrelorbeenusedinthecontrolarm.However,todate,thelargesttrialofprasugrelpretreatment,ACCOAST,wasterminatedbytheDSMBforlackofefficacyandexcessbleeding.Thus,oralpretreatment,whilebiologicallyappealingandintuitive,remainsunproveninprospectiverandomizedclinicaltrials.LimitationsA loading dose of 6ConclusionsInCHAMPIONPHOENIX,intravenousADPreceptorantagonismwithcangrelorsignificantly(p=0.005)reducedthecompositeofdeath,myocardialinfarction,ischemia-drivenrevascularization,orstentthrombosisat48hours,witha22%oddsreduction.Thekeysecondaryendpointofstentthrombosiswasalsosignificantlyreduced,witha38%oddsreduction.Thebenefitwassustainedthrough30days.Therewasnoexcessinseverebleedingortransfusions.IntravenouscangrelormaybeanattractiveoptionacrossthefullspectrumofPCI,includingstableangina,NSTEMI,andSTEMI.ConclusionsIn CHAMPION PHOENIXForFullDetails,PleaseGotowww.NEJM.orgBhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgFor Full Details,Please Go toTHANKYOU!THANK YOU!BACKUPSLIDESBACKUP SLIDESCangrelorDirectplateletP2Y12receptorantagonistATPanalogueMW=800DaltonsParenteraladministrationT1/2=3to6minutesOffset=60minutesNNNNNHSCF3OHOHOOPOOPPOOOClClOOOS4Na+AngiolilloDJ,SchneiderDJ,BhattDL,etal.Pharmacodynamiceffectsofcangrelorandclopidogrel:theplateletfunctionsubstudyfromthecangrelorversusstandardtherapytoachieveoptimalmanagementofplateletinhibition(CHAMPION)trials.JThrombThrombolysis2012;34:44-55.CangrelorDirect platelet P2Y12CHAMPIONPCI|PLATFORMPCI|allcomersPCI|58%ACS|onclopidogrelallowed|clopidogrel600mgadministeredatthestartofPCIinthecontrolarmPLATFORM|allcomersPCI|65%ACS|clopidogrelnave|clopidogrel600mgadministeredattheendofPCIinthecontrolarm12hours0PCI25Cangrelor30 g/kgthen4 g/kg/minCangrelor30 g/kgthen4 g/kg/minClopidogrel600mgoralClopidogrel600mgoralCHAMPIONPCIN=9000SA/UA/ACS/STEMIOnclopidogrelallowedCHAMPIONPLATFORMN=6400SA/UA/ACSNoclopidogrelallowedHarringtonRA,etal.NEJM2009BhattDL,etal.NEJM2009CHAMPION PCI|PLATFORMPCI|a48-HourEventsPLATFORMOR95%CIPvalueDeath/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.AHJ2012.48-Hour EventsOR 95%CIP valCHAMPIONPHOENIXLessonsfromCHAMPIONPCI|PLATFORMTrialDesignImplementationPatientpopulationAllcomersPCIInclusionofpatientswithnormalcardiacmarkersatbaseline|est.65%trialpopulationP2Y12inhibitornavePatientsnotpre-treatedwithP2Y12inhibitorwithin7dayspriortoangiogramEndpointdefinitionsMIdefinition1UDMI|CentrallabtoassureconsistencyofCKMBmassassayglobally|angiographiccorelabtoconsistentlyassessevidenceofischemiaStentthrombosisdefinition2ARCDefinitionincludesoccurrenceassociatedwithIDR|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;6:3643.CHAMPION PHOENIXLessons from CUniversalDefinitionofMIThygesenK,AlpertJS,andWhiteHD,onbehalfoftheJointESC/ACCF/WHFTaskForcefortheRedefinitionofMyocardialInfarction.Universaldefinitionofmyocardialinfarction.EurHeartJ.2007;28:2525-2538.BetterdiscriminationofMIwithconsiderationofmultiplecriteriaCKMBelevations|ischemicsymptoms|angiographicevidence|ECGchangesDiagnosisofMIfromvariousperspectivesType1|spontaneousMIrelatedtoischemiaType2|MIsecondarytoischemia|changeinO2demand/supplyType3|suddenunexpectedcardiacdeathType4|associatedwithcoronaryangioplasty|stentsType4a|MIassociatedwithPCIType4b|MIassociatedwithStentThrombosisType5|MIassociatedwithCABGUniversal Definition of MI ThyDefinitionofSTAngiographicEvidence:ARCST(AcademicResearchConsortium)1Acute(24hoursand30days)DefinitefromprobablestentthrombosisAdjudicatedbytheCECIPST(Intra-proceduralstentthrombosis)NeworworseningthrombusrelatedtothestentorAbruptclosureduetothrombosis1.CutlipDE,WindeckerS,MehranR,etal.Clinicalendpointsincoronarystenttrials:acaseforstandardizeddefinitions.Circulation2007;115(17):2344-2351.Definition of STAngiographic ESampleSizeEstimationEventrateof5.1%intheclopidogrelarmand3.9%inthecangrelorarm(24.5%reductioninoddsratio)N=10,900(powerof85%todetectthisdifferenceattheonesidedsignificancelevelof0.025)BhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgSample Size EstimationEvent raMDCOClinical+DataOperationsLEADERSHIPJennaBisch(ProjectLead)TracySurvill(DataLead)TiepuLiu(Statistician)SteveElkin(Programming)MarkusDietrich(Medical)PROJECTMANAGEMENTDeniseEvansTaraRichardsonNitaWhyteIN-HOUSEOPERATIONSDanielBoisvertKathieVolcyLaurenEnsleyMariluMontalvoDATAMANAGEMENTCindyCleggKalpanaPullakhandamMichelleArthurGretchenCleggPamHoffmanKathleenTencerJuliaBaughSowersLucyWangunyuLindaConnollyCindyLazosSITEMANAGEMENTCOLsPeterDjuricCynthiaShadeMohammadArifLindaTilbergKateyFoxCRAsChristinaGerhardtScottStephensLetiVillafrancaKareyCropperLindaWillitsValMorrowMDCO Clinical+Data OperationCHAMPIONPHOENIXAROsandCROsPartnersRoleAlmacIVRS/IWRSMergeeCRFQuestCKMBcentrallabBioclinicaWebportalforangiographicfilmuploadsCardiovascularResearchFoundationAngiographicCoreLabDukeClinicalResearchInstituteCECGreenLaneCoordinatingCenterSiteManagementNewZealandWorldwideClinicalTrialsSiteManagementROWexcl.US+NZMDCOSiteManagement-USCHAMPION PHOENIX AROs and CROsPatientDispositionEnrolledpatientswithStableAngina/NSTE-ACS/STEMIIndicatedforPCI(N=11,145)1:1RandomizationITTCANGRELOR(N=5581)ITTCLOPIDOGREL(N=5564)NoPCI(N=91)DidNotReceiveStudyDrug(N=52)NoPCI/NoStudyDrug(N=109)NoPCI(N=83)DidNotReceiveStudyDrug(N=37)NoPCI/NoStudyDrug(N=94)MITTCANGRELOR(N=5472)MITTCLOPIDOGREL(N=5470)Losttofollow-up(N=2)WithdrewConsent(N=1)48hourfollow-up(N=5470)48hourfollow-up(N=5469)Losttofollow-up(N=8)Losttofollow-up(N=9)30dayfollow-up(N=5462)30dayfollow-up(N=5457)PCIPCIPatient DispositionEnrolled paPrimaryEfficacyOutcomeat48Hours,MITTCangrelor(N=5472)Clopidogrel(N=5470)OR(95%CI)P-valuePrimaryAnalysisAdjusted1Death/MI/IDR/ST257/5470(4.7%)322/5469(5.9%)0.78(0.66,0.93)0.005ClopidogrelLoading300mg81/1405(5.8%)95/1401(6.8%)0.84(0.62,1.14)0.27600mg176/4065(4.3%)227/4068(5.6%)0.77(0.63,0.94)0.0091.Thelogisticmodelwasadjustedforbaselinestatusandclopidogreldose.BhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgPrimary Efficacy Outcome at 48EfficacyOutcomesat48Hours,ITTCangrelor(N=5581)Clopidogrel(N=5564)OR(95%CI)PValueDeath/MI/IDR/ST(primaryendpoint,adjusted)260/5573(4.7%)325/5561(5.8%)0.79(0.67,0.93)0.005Stentthrombosis(keysecondaryendpoint)46/5573(0.8%)74/5561(1.3%)0.62(0.43,0.89)0.01MI207/5573(3.7)255/5561(4.6)0.80(0.67,0.97)0.02Q-waveMI11/5573(0.2)18/5561(0.3)0.61(0.29,1.29)0.19IDR29/5573(0.5)38/5561(0.7)0.76(0.47,1.23)0.27Death20/5573(0.4)21/5561(0.4)0.95(0.51,1.75)0.87CVDeath20/5573(0.4)21/5561(0.4)0.95(0.51,1.75)0.87BhattDL,StoneGW,MahaffeyKW,etal.HarringtonRA.NEJM2013atwww.nejm.orgEfficacy Outcomes at 48 Hours,
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