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CHAMPIONPHOENIXDeepakL.Bhatt,MD,MPH,GreggW.Stone,MD,KennethW.Mahaffey,MD,C.MichaelGibson,MS,MD,Ph.GabrielSteg,MD,Chri

stianHamm,MD,MatthewPrice,MD,SergioLeonardi,MD,DianneGallup,MS,MeredithTodd,SimonaSkerjanec,PharmD,HarveyD.White,DSc,andRobertA.Harring

ton,MD,onbehalfoftheCHAMPIONPHOENIXInvestigatorsDr.Bhatt–AdvisoryBoard:MedscapeCardiology;BoardofDirectors:BostonVAResearchInstitute,

SocietyofChestPainCenters;Chair:AmericanHeartAssociationGetWithTheGuidelinesScienceSubcommittee;Honoraria:AmericanCollegeofCardiology

(Editor,ClinicalTrials,Cardiosource),DukeClinicalResearchInstitute(clinicaltrialsteeringcommittees),

SlackPublications(ChiefMedicalEditor,CardiologyTodayIntervention),WebMD(CMEsteeringcommittees);Other:SeniorAssociateEditor,Jou

rnalofInvasiveCardiology;ResearchGrants:Amarin,AstraZeneca,Bristol-MyersSquibb,Eisai,Ethicon,Medtronic,San

ofiAventis,TheMedicinesCompany;UnfundedResearch:FlowCo,PLxPharma,Takeda.Thispresentationincludesoff-labeland/orinve

stigationalusesofdrugs,includingclopidogrelandcangrelor.TheCHAMPIONPHOENIXtrialwasfundedbyTheMedicinesCompany.DisclosuresAntipla

teletTherapy►AntiplatelettherapyisacriticalpartofcontemporaryPCI.►Intheeraofaspirinandunfractionatedheparin,intrav

enousglycoproteinIIb/IIIainhibitionsignificantlyreducedimportantperiproceduralischemicevents,butsignificantlyincreasedblee

ding.►ADPreceptorantagonismwithoralagentswasalsoshowntoreduceischemiceventsinPCIandespeciallyACS.►However,availableoralagentsarelimite

dbytheirrelativelylongdurationofactionandbioavailability,whichmightbealiability:▪ifgivenpriortocoronaryangiographyandurgentoremergentCABGisdee

mednecessary,▪insituationswhereabsorptionmaybeproblematic,suchaswithrapidtimestoPCI,▪inpatientswhoareintubated,nauseated,withSTEMI,orshock

.HarringtonRA,etal.PURSUIT.NEJM1998DesaiNandBhattDL.PeriproceduralAntiplateletTherapy.JACCIntervention2010Cangrelor►CangrelorisanintravenousAD

Preceptorantagonistthatisrapidlyacting,potent,andreversible,withreturnofnormalplateletfunctionwithinanhour.

►CangrelorwasstudiedpreviouslyintwolargePhase3PCItrials,CHAMPIONPCIandCHAMPIONPLATFORM.Neitherstudymetitspri

maryendpoint,butthesecondaryendpointofstentthrombosisat48hourswassignificantlyreducedinCHAMPIONPLATFORMandinaprespecifiedpooledanalys

isofthetwotrials.Therewasnoexcessinseverebleeding.►ThepotentialefficacysignalpromptedustolaunchtheCHAMPIONPHOENIX

trial.HarringtonRA,etal.CHAMPIONPCI.NEJM2009BhattDL,etal.CHAMPIONPLATFORM.NEJM2009WhiteHD,etal.Meta-Analysi

sofCHAMPIONPCIandPLATFORM.AHJ2012CHAMPIONPHOENIXExecutiveCommitteeDeepakL.Bhatt,M.D.,M.P.H.(Co-PrincipalInvestigator)VA

BostonHealthcareSystem,BrighamandWomen'sHospital,andHarvardMedicalSchoolBoston,MARobertA.Harrington,M.D.(Co-PrincipalInvestiga

tor)DepartmentofMedicine,StanfordUniversity,Stanford,CAC.MichaelGibson,M.S.,M.D.BethIsraelDeaconessMedicalCenter,DivisionofCardiology,B

oston,MAChristianW.Hamm,M.D.KerckhoffHeartandThoraxCenter,BadNauheim,GermanyKennethW.Mahaffey,M.D.DukeClinicalResearchInstitute,Durh

am,NCMatthewJ.Price,M.D.ScrippsClinicandScrippsTranslationalScienceInstitute,LaJolla,CAPh.GabrielSteg,M.D.INSERMU-698,Un

iversitéParis-Diderot,andHôpitalBichat,Assistance-Publique-HôpitauxdeParis,Paris,FranceGreggW.Stone,M.D.ColumbiaUniversityMedicalCenterand

theCardiovascularResearchFoundation,NewYork,NYHarveyD.White,D.Sc.AucklandCityHospital,Auckland,NewZealandCHAMPIONPHOENIXDSMBFransVandeWerf,M.D.(Chai

r)UniversitairZiekenhuisGasthuisberg,BelgiumDavidP.Faxon,M.D.Brigham&Women’sHospital,Dept.ofMedicine,Boston,MAE.MagnusOh

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

AmsterdamW.DouglasWeaver,M.D.HenryFordHospital,Detroit,MIJanG.P.Tijssen,Ph.D.(Statistician)DepartmentofCardiol

ogy,AcademicMedicalCenter-UniversityofAmsterdam,TheNetherlandsCHAMPIONPHOENIXCECDukeClinicalResearchInstituteREVIEWERSPhase1Lucian

aAmaganijanBrazilMoniqueAndersonNCAkshayBagaiNCRobertW.HarrisonNCPedroG.MelodeBarrosESilvaBrazilPhase2J.MatthewBrenna

nNCRenatoD.LopesNCChiaraMelloniNCPierluigiTricociNCLEADERSHIPKennethW.Mahaffey(Chair)SergioLeonardi(co-Chair)DianneGallup(LeadStatistician)MatthewD.

Wilson(ProjectLeader)OPERATIONSStaceyMangum(Coordinator)LindaDowd(LeadCDA)DimitriosStournaras(LeadCDS)SachinVyas(LeadCTA)CHAM

PIONPHOENIXAngiographicCoreLabCardiovascularResearchFoundationMariaAlfonsoAntoinetteAllenGerardCondittRosaDeJesusChampikaDjurkovicShar

watJahanGregKaluzaElenaKonovalovaMitchellLustreKatharineLymberisDuvalMichelSofiaPapamitrouNicolettaPavloviciKharyPer

rySairaPunjwaniConnieQiuRaquelSanchezEliasSanidasShawnaleeVassellDoueyWrightReviewersandDataEntryStaffLeadershipPhilippeG

énéreux(Director)SorinBrenerLauraLasalle12Countries│153SitesUSAPolandGermanyAustriaThailandRussiaGeorgiaBulgariaBrazilCzechRepub

licUSAPolandGermanyNewZealandAustriaItalyThailandRussiaGeorgiaBulgariaBrazilCHAMPIONPHOENIX–AGlobalTrialCHAMPIONPHOENIXStudyDesign►Randomized,do

uble-blind,double-dummy,superiority►Primaryefficacyendpoint:Death/MI/IDR/STat48hours▪Adjustedfor600mg

versus300mgclopidogreluse▪ModifiedIntent-to-Treat(MITT)analysis(patientsactuallygotstudydrugandPCI)►K

eysecondaryendpoint:StentThrombosisat48hours►Efficacyendpointsalsoexaminedat30days►Primarysafetyendpoint:GUSTOSevereBleed

ingat48hoursHarringtonRA,etal.CHAMPIONPCI.NEJM2009BhattDL,etal.CHAMPIONPLATFORM.NEJM2009WhiteHD,etal.Meta-AnalysisofCHAMPIONPCIandPLATFORM.AHJ201

2CHAMPIONPHOENIXStudyDesign12to4hours0Cangrelor2bolus&infusion(30ug/kg;4ug/kg/min)Clopidogrel600mgoralCHAMPIONPHOENIXN=10,900MITTSA

/NSTE-ACS/STEMIPatientsrequiringPCI1P2Y12inhibitornaïveORPlacebo3oral(rightbeforePCIorrightafter,perphysician)P

lacebo2bolus&infusionPlacebooralPCI~30’ORClopidogrel3(600mgor300mgoral,perphysician)1Randomizationoccurr

edoncesuitabilityforPCIwasconfirmedeitherbyangiographyorSTEMIdiagnosis.Doubleblindstudymedicationwasadministeredassoonaspossi

blefollowingrandomization.2StudydrugInfusion(cangrelorormatchingplacebo)wascontinuedfor2-4hoursatthediscretionofthetreatingphy

sician.Attheendoftheinfusionpatientsreceivedaloadingdoseofclopidogrelormatchingplaceboandweretransitionedtomaintenanceclopidogreltherapy.3Clopido

grelloadingdose(ormatchingplacebo)wasadministeredasdirectedbytheinvestigator.Atthetimeofpatientrandomization,aclopidogrelload

ingdoseof600mgor300mgwasspecifiedbytheinvestigator.MITT=modifiedintent-to-treat;NSTE-ACS=non-ST-elevationacuteco

ronarysyndrome;PCI=percutaneouscoronaryintervention;SA=stableangina;STEMI=ST-elevationMI.RandDemographics,MITTCangrelor(N=5472)Clopidogrel(

N=5470)Age,years6464Female28%27%Diabetesmellitus28%28%PatientTypeStableangina57%55%NSTE-ACS25%26%STEMI18%19%LoadingDose300mgclop

idogrel26%26%600mgclopidogrel74%74%RegionUnitedStates37%37%Othercountries63%63%PrimaryEfficacyOutcomesat48Hours,MITTCan

grelor(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.Thelogistic

modelwasadjustedforbaselinestatusandclopidogreldose.Pvalueof0.006shownontheKMcurveislogrankpvalue.SecondaryEf

ficacyOutcomesat48Hours,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)0.22D

eath18/5470(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,St

oneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgDeath/MI/IDR/StentThrombosiswithin48HoursPatientatRiskHoursfromRando

mizationCangrelor:547252335229522552235221522052175213Clopidogrel:547051625159515551525151515151475147cangrelorclopidogrel5.9%4.7%LogR

ankPValue=0.006EventRate(%)BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgcangrelorclopidogrelLogRankPValue=0.01PatientatRi

skHoursfromRandomizationCangrelor:547254265421541954195418541754165414Clopidogrel:5470539253895388538653855385538353831.4%0.

8%EventRate(%)StentThrombosiswithin48HoursBhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgEfficacyOutcomesat30Days,MITTCangrelo

r(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)0.36Death

60/5462(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.orgOR[95%CI]P[Int]Overall0.79(0.67,0.93)Age≥750.71(0.50,1.02)0.55Age<750.81(0.67,0.98)Male0.84(0.6

9,1.03)0.23Female0.67(0.50,0.92)Ethnicity:White0.80(0.67,0.95)0.72Ethnicity:Non-white0.70(0.35,1.41)Unit

edStates0.70(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)0.35BiomarkerNega

tive0.75(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-Dep

endentDiabetes: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/STat48Hour

sCangrelorBetterClopidogrelBetterOR[95%CI]P[Int]PriorTIA/Stroke0.78(0.37,1.63)0.97NoPriorTIA/Stroke0.79(0.66,0.94)HistoryofP

AD0.36(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)0.99ClopidogrelLoa

dafterPCIStart0.79(0.59,1.06)Cangrelorinfusion≤129minutes0.85(0.68,1.07)0.31Cangrelorinfusion>129minute

s0.72(0.56,0.92)Subgroups:Death/MI/IDR/STat48Hours(continued)5.01.00.2CangrelorBetterClopidogrelBetterNon-CABGBleedingat48Hours,Sa

fetyBleedingScaleCangrelor(N=5529)Clopidogrel(N=5527)OR(95%CI)PValueGUSTOSevere9(0.16%)6(0.11%)1.50(0.53,4.22)0.44GUSTOMode

rate22(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)>0.999TIMIMi

nor9(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)0.16ACUITYMajo

r235(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,Ma

haffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgOR[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(0.5

2,7.86)BiomarkerPositive1.51(0.64,3.53)0.79BiomarkerNegative1.76(0.81,3.82)DiabeticNo1.90(0.88,4.09)0.56Diab

eticYes1.35(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)0.35NoPr

iorMI1.44(0.78,2.67)ClopidogrelBetterSubgroups:GUSTOSevere/ModerateBleeding,Safety5.01.00.2CangrelorBetterSubgroups:GUS

TOSevere/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)0.26Heparin

only1.89(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-Elu

tingStent1.26(0.57,2.77)0.35Bare-MetalStent2.17(0.93,5.03)Aspirin≤100mg1.58(0.52,4.85)0.93Aspirin>100

mg1.49(0.74,3.03)ClopidogrelLoadbeforePCIStart1.24(0.58,2.66)0.25ClopidogrelLoadafterPCIStart2.53(0.9

8,6.54)Cangrelorinfusion≤129minutes1.71(0.81,3.59)0.85Cangrelorinfusion>129minutes1.52(0.62,3.73)Sum

maryofTreatmentEmergentAdverseEventsAdverseEventCangrelor(N=5529)Clopidogrel(N=5527)PValuePatientswit

hatleastoneAE20.2%19.1%0.13PatientswithatleastoneAEcausingstudydrugdiscontinuation0.5%0.4%0.21Transientdyspnea1.2%0.3%<0.001BhattDL,StoneGW,Ma

haffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgLimitations►Aloadingdoseof600mghasbecomemorecommonthan300mg▪However,inth

ethreequartersofpatientswhoreceived600mg,thebenefitofcangrelorremainedstatisticallysignificantandwasnotattenu

ated.►Itispossiblethebenefitswesawherewouldhavebeenattenuatedwithalongerdurationofpretreatment.▪Ofnote,theclopidogrelpretreatmentwasgiven“o

nthetable”asisconsistentwithmanypracticesaroundtheworldandinparticularintheUnitedStates.▪Importantly,prospe

ctiverandomizedclinicaltrials,namelyCREDOandPRAGUE-8,didnotfindasignificantbenefitforclopidogrelpretrea

tment.►Thebenefitsseenheremayalsohavebeenattenuatedhadprasugrelorticagrelorbeenusedinthecontrolarm.▪However,todate,t

helargesttrialofprasugrelpretreatment,ACCOAST,wasterminatedbytheDSMBforlackofefficacyandexcessbleeding.▪

Thus,oralpretreatment,whilebiologicallyappealingandintuitive,remainsunproveninprospectiverandomizedclinicaltrials.Conclusi

ons►InCHAMPIONPHOENIX,intravenousADPreceptorantagonismwithcangrelorsignificantly(p=0.005)reducedthecompositeofdeath,myocardialinfarction,is

chemia-drivenrevascularization,orstentthrombosisat48hours,witha22%oddsreduction.►Thekeysecondaryendpointofstentt

hrombosiswasalsosignificantlyreduced,witha38%oddsreduction.►Thebenefitwassustainedthrough30days.►Therewasnoexcessinseverebleedingortrans

fusions.►IntravenouscangrelormaybeanattractiveoptionacrossthefullspectrumofPCI,includingstableangina,NSTEMI,andSTEMI.ForFullDetails,

PleaseGotowww.NEJM.orgBhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.orgTHANKYOU!BACKUPSLIDESCangrelor►Directplatele

tP2Y12receptorantagonist►ATPanalogueMW=800Daltons►Parenteraladministration►T1/2=3to6minutes►Offset=60min

utesNNNNNHSCF3OHOHOOPOOPPOOOClClOOOS4Na+AngiolilloDJ,SchneiderDJ,BhattDL,etal.Pharmacodynamiceffectsofcangrelorandclopidogrel:theplatelet

functionsubstudyfromthecangrelorversusstandardtherapytoachieveoptimalmanagementofplateletinhibition(CHAMPION)trials.JThrombThrombolysis201

2;34:44-55.CHAMPIONPCI|PLATFORM►PCI|allcomersPCI|58%ACS|onclopidogrelallowed|clopidogrel600mgadministeredatthestartofPCIinthecontrolarm►PL

ATFORM|allcomersPCI|65%ACS|clopidogrelnaïve|clopidogrel600mgadministeredattheendofPCIinthecontrolarm12hours0PC

I~25’Cangrelor30g/kgthen4g/kg/minCangrelor30g/kgthen4g/kg/minClopidogrel600mgoralClopidogrel600mgoralCHAMPIONPCIN=9000SA/UA/ACS

/STEMIOnclopidogrelallowedCHAMPIONPLATFORMN=6400SA/UA/ACSNoclopidogrelallowedHarringtonRA,etal.NEJM2009BhattDL,etal.NEJM200948-HourEventsPLATFOR

MOR[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)0.00

3PCIDeath/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)0.004CangrelorBetter5.02.01.00.20.5

ComparatorBetterSummaryofClinicalEfficacy1.BhattDL,LincoffAM,GibsonCM,etal.Intravenousplateletblockadewithc

angrelorduringPCI.NEnglJMed2009;361:2330-41.2.HarringtonRA,StoneGW,McNultyS,etal.Plateletinhibitionwithcangrelorinpatient

sundergoingPCI.NEnglJMed2009;361:2318-29.3.WhiteHD,ChewDP,DauermanHL,etal.AHJ2012.CHAMPIONPHOENIXLessonsfromCHAMPIONPCI|PLATFORMTrialDesignI

mplementationPatientpopulationAllcomersPCIInclusionofpatientswithnormalcardiacmarkersatbaseline|est.65%trialpopulationP2Y12inhibitornaïvePatientsn

otpre-treatedwithP2Y12inhibitorwithin7dayspriortoangiogramEndpointdefinitionsMIdefinition1UDMI|Centrallabtoassu

reconsistencyofCKMBmassassayglobally|angiographiccorelabtoconsistentlyassessevidenceofischemiaStentthrom

bosisdefinition2ARCDefinitionincludesoccurrenceassociatedwithIDR|Death|MI|alsointra-proceduralstentthrombosismeasuredbyangiographiccorela

b31.ThygesenK,AlpertJS,andWhiteHD,onbehalfoftheJointESC/ACCF/WHFTaskForcefortheRedefinitionofMyocardialInfar

ction.Universaldefinitionofmyocardialinfarction.EurHeartJ.2007;28:2525-2538.2.CutlipDE,WindeckerS,MehranR,etal.Clinicalendpoints

incoronarystenttrials:acaseforstandardizeddefinitions.Circulation2007;115:2344-2351.3.BrenerSJ,CristeaE,KirtaneAJ,etal.Intra-ProceduralStentThro

mbosis.JAmCollCardiolIntv2013;6:36–43.UniversalDefinitionofMIThygesenK,AlpertJS,andWhiteHD,onbehalfoftheJointESC/ACCF/WHFTaskForcefortheRedefinitiono

fMyocardialInfarction.Universaldefinitionofmyocardialinfarction.EurHeartJ.2007;28:2525-2538.Betterdiscrimi

nationofMIwithconsiderationofmultiplecriteriaCKMBelevations|ischemicsymptoms|angiographicevidence|ECGchangesDi

agnosisofMIfromvariousperspectivesType1|spontaneousMIrelatedtoischemiaType2|MIsecondarytoischemia|changein

O2demand/supplyType3|suddenunexpectedcardiacdeathType4|associatedwithcoronaryangioplasty|stentsType4a|MIa

ssociatedwithPCIType4b|MIassociatedwithStentThrombosisType5|MIassociatedwithCABGDefinitionofSTAngiographicEvidence:ARCST

(AcademicResearchConsortium)1►Acute(<24hourspost-procedure)►Subacutestentthrombosis(>24hoursand≤30days)▪Definite

fromprobablestentthrombosis▪AdjudicatedbytheCECIPST(Intra-proceduralstentthrombosis)►Neworworseningthrombusrelatedtothestentor►Abru

ptclosureduetothrombosis1.CutlipDE,WindeckerS,MehranR,etal.Clinicalendpointsincoronarystenttrials:acaseforstandardizeddefinitions.Circulation2007;115

(17):2344-2351.SampleSizeEstimation►Eventrateof5.1%intheclopidogrelarmand3.9%inthecangrelorarm(24.5%reductioninoddsratio)►N=

10,900(powerof85%todetectthisdifferenceattheonesidedsignificancelevelof0.025)BhattDL,StoneGW,MahaffeyKW,etal….Harrin

gtonRA.NEJM2013atwww.nejm.orgMDCOClinical+DataOperationsLEADERSHIPJennaBisch(ProjectLead)TracySurvill(DataLead)TiepuLiu(St

atistician)SteveElkin(Programming)MarkusDietrich(Medical)PROJECTMANAGEMENTDeniseEvansTaraRichardsonNit

aWhyteIN-HOUSEOPERATIONSDanielBoisvertKathieVolcyLaurenEnsleyMariluMontalvoDATAMANAGEMENTCindyCleggKalpanaPullakhandamMichelleArthurGretchenCleggP

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ment–NewZealandWorldwideClinicalTrialsSiteManagement–ROWexcl.US+NZMDCOSiteManagement-USPatientDispositionEnrolledpatientswithStableAngina/NSTE-ACS/ST

EMIIndicatedforPCI(N=11,145)1:1RandomizationITTCANGRELOR(N=5581)ITTCLOPIDOGREL(N=5564)NoPCI(N=91)DidNotReceiveS

tudyDrug(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)PCIPCIPrimaryEfficacyOutcomeat48Hours,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)0.005ClopidogrelLoadin

g300mg81/1405(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)0.0

091.Thelogisticmodelwasadjustedforbaselinestatusandclopidogreldose.BhattDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.

orgEfficacyOutcomesat48Hours,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)0.87Bha

ttDL,StoneGW,MahaffeyKW,etal….HarringtonRA.NEJM2013atwww.nejm.org