13PARTNERTrialPresentationSlides

VinodH.Thourani,MDonbehalfofThePARTNERTrialInvestigatorsThree-YearOutcomesafterTranscatheterorSurgicalAorticValveReplacementinHigh-RiskPatientswithSevereAorticStenosisACC2013|SanFrancisco|March11,2013•Grant/ResearchSupport•ConsultingFees/Honoraria•MajorStockShareholder/Equity•Ownership/Founder•IntellectualPropertyRights•EdwardsLifesciences,SorinMedical•SorinMedical,St.JudeMedical•ApicaCardiovascular•ApicaCardiovascular•ApicaCardiovascularWithinthepast12months,Iormyspouse/partnerhavehadafinancialinterest/arrangementoraffiliationwiththeorganization(s)listedbelow.Affiliation/FinancialRelationshipCompanyDisclosureStatementofFinancialInterestBackground•TherandomizedPARTNERtrialdemonstratedthattranscatheteraorticvalvereplacement(TAVR)resultedinsimilarmortalitycomparedwithsurgicalAVRatoneyearinpatientswhowerehigh-risksurgicalcandidates.•LongertermoutcomesfollowingTAVRareunknownandarenecessarytoassessvalveperformanceandtoanalyzelatecomplicationsbeforeTAVRcanbeappliedmorewidely.PublicationsinNEJM1-Yearoutcomespublishedon-lineJune5,[e-mail]9,20112-Yearoutcomespublishedon-lineMarch26,[e-mail]3,2012PurposeInpatientswithsevereASathigh-riskforsurgery,randomizedtoeitherTAVRorsurgicalAVR,after≥3yearsfollow-up,toassess:–mortality,strokeandotherclinicaloutcomes–clinicalandproceduralpredictorsofmortality–valveperformancebyechocardiographyN=179N=358InoperableStandardTherapyASSESSMENT:TransfemoralAccessNotInStudyTFTAVRPrimaryEndpoint:All-CauseMortalityOverLengthofTrial(Superiority)Co-PrimaryEndpoint:CompositeofAll-CauseMortalityandRepeatHospitalization(Superiority)1:1RandomizationVSYesNoN=179TFTAVRAVRPrimaryEndpoint:All-CauseMortalityat1yr(Non-inferiority)TATAVRAVRVSVSN=248N=104N=103N=244PARTNERStudyDesignSymptomaticSevereAorticStenosisASSESSMENT:High-RiskAVRCandidate3,105TotalPatientsScreenedTotal=1,057patients2ParallelTrials:IndividuallyPoweredN=699HighRiskASSESSMENT:TransfemoralAccessTransapical(TA)Transfemoral(TF)1:1Randomization1:1RandomizationYesNoInclusionCriteria*•SevereAS:Echo-derivedAVA0.8cm2(orAVAindex0.5cm2/m2)andmeanAVG40mmHgorpeakjetvelocity4.0m/s•CardiacSymptoms:NYHAFunctionalClass≥II•Highsurgicalrisk:Predictedriskofoperativemortality≥15%(determinedbysitesurgeonandcardiologist);guideline=STSScore≥10*Smith,C.R.,etal.,TranscatheterversusSurgicalAortic-ValveReplacementinHigh-RiskPatients.NEnglJMed,2011.364(23):p.2187-98.KeyExclusionCriteria•Aorticannulusdiameter(echomeasurement)18mmor25mm•Iliac-femoralanatomyprecludingsafesheathinsertion•SevereLVdysfunction(LVEF20%)•UntreatedCADrequiringrevascularizationAnatomic:•SerumCr3.0mg/dLordialysisdependent•AcuteMIwithin1month•CVAorTIAwithin6months•HemodynamicinstabilityClinical:StudyDevicesEdwardsSAPIENTHV23and26mmvalvesRetroFlex22and24FsheathsAscendra24and26FsheathsTransfemoralTransapicalEnrollingStudySitesIntermountainMedicalCenterSaltLakeCity,UTEmoryUniversityAtlanta,GAUniv.ofMiamiMiami,FLUniv.ofVirginiaCharlottesville,VASt.Luke’sHospitalKansasCity,MOBarnes-JewishHospitalSt.Louis,MOMedicalCityDallasDallas,TXSt.Paul'sHospitalVancouver,CanadaUniv.ofWashingtonSeattle,WAMayoClinicRochester,MNStanfordUniversityPaloAlto,CAHospitalLavalQuebecCity,CanadaOchsnerFoundationNewOrleans,LAScrippsClinicLaJolla,CACedars-SinaiMedicalCenterLosAngeles,CAClevelandClinicCleveland,OHColumbiaUniversityCornellUniversityNewYork,NYWashingtonHosp.CenterWash.,DCUniv.ofPennPhila.,PABrigham&Women’sMassGeneralBoston,MANorthwesternUniv.Chicago,ILEvanstonHospitalLeipzigHeartCenterLeipzig,Germanyn=699patients25investigatorsites22USA,2Canada,1GermanyKeyEnd-Points•All-causemortality(primaryendpoint)•Cardiovascularmortality•Rehospitalization•Strokes•Vascularandbleedingevents•NYHAfunctionalclass•Echocardiographicmeasuresofvalveperformance(includingvalvegradients/areasandpost-proceduralaorticregurgitation)StudyMethodology•Allpatientsfollowedforatleastthreeyears•Primaryanalysisperformedbyintention-to-treat(ITT),althoughas-treated(AT)analysesperformedwhenappropriate(e.g.echodata=AT)•EventratesasKaplan-Meierestimates,withgroupscomparedbylog-rankoverthelengthoffollow-up•Compositeanalysespre-specified•Effectofbaselinevariableson3-yrmortalitystudiedwithCoxproportionalhazardsregression(multivariableanalysiswithcovariatesp-value0.20)•Effectofproceduralcomplicationson3-yrmortalitystudiedwithtime-dependentcovariateanalysisStudyFlow3YearsAlive=132Dead=96LTFU=3Withdrawal=3OngoingF/U=103YearsAlive=119Dead=101LTFU=3Withdrawal=17OngoingF/U=8AVR(248)Randomized=699patientsTF=492(70%)TA=207(30%)Transfemoraln=492TAVR(244)3YearsAlive=45Dead=52LTFU=1Withdrawal=0OngoingF/U=63YearsAlive=47Dead=42LTFU=1Withdrawal=10OngoingF/U=3AVR(103)Transapicaln=207TAVR(104)86.5%follow-upat3years92.2%follow-upat3years91.5%follow-upat3years91.0%follow-upat3yearsBaselinePatientCharacteristicsDemographicsCharacteristicTAVR(n=348)AVR(n=351)nnAge–years(Mean±SD)34883.6±6.834984.5±6.4Male20157.8%19856.7%NYHAClassIIIorIV32894.3%32894.0%PreviousCABG14842.515243.6Cerebrovasculardisease9629.48726.8Peripheralvascular