外科治疗缺血性心力衰竭STICH的研究

外科治疗缺血性心力衰竭STICH的研究STICHFinancialDisclosuresOriginalRecipientInstitutionPrincipalInvestigatorActivityDukeUniversityMedicalCenterRobertH.JonesClinicalCoordinatingCtrDukeUniversityMedicalCenterKerryL.LeeStatisticalandDataCCDukeUniversityMedicalCenterDanielB.MarkEQOLCoreLaboratoryUnivofAlabama-BirminghamGeraldM.PohostCMRCoreLaboratoryMayoClinicJaeK.OhECHOCoreLaboratoryUniversityofPittsburghArthurM.FeldmanNCGCoreLaboratoryNorthwesternUniversityRobertO.BonowRNCoreLaboratoryWashingtonHospitalCenterJulioA.PanzaDECIPHERSubstudyBaylorUniversityMedicalCtrPaulGrayburnMRTEESubstudyFundingSources:NationalHeart,LungandBloodInstitute97.3%

ChaseMedical0.3%AbbottLaboratories2.3%

CVTherapeutics0.1%CoreSTICHStudyOrganizationPrincipalInvestigator:RobertHJonesCo-Principalinvestigator:EricVelazquezDCCPrincipalInvestigator:KerryLLeeStudyChair:JeanLRouleauExecutiveCommittee:RobertHJones,EricVelazquez,KerryLLee,JeanLRouleau,PatriceDesvigne-Nickens,GeorgeSopko,ChrisO’Connor,RobertMichler,andJaeOh.DSMBchair:SidGoldsteinPublicationsCommitteechair:JamesHillClinicalEndpointsCommittee:PeterCarsonHypothesis2EnrollmentbyCountry

1000patients

96clinicalsites

23countries

1231daysRandomizedPatientsNumbersforAnalysis

byHypothesisMED

+

CABG

(610)MED

+

CABG

(499)CAD,EF0.35EligibleforMED-onlytreatment?EligibleforSVR?NotintrialNoHypothesis1

n=1212Hypothesis2

n=1000MED

(602)MED

+

CABG

+

SVR(501)StratumA

n=10611MED

(527)2MED

+

CABG

(534)EligibleforSVR?StratumC

n=859Yes6MED

+

CABG

(423)7MED

+

CABG

+

SVR(436)StratumB

n=2163MED

(75)5MED

+

CABG

+

SVR(65)4MED

+

CABG

(76)+2136 Randomizedpts=++

602 MEDonly1033 CABGadded

501 CABG+SVRadded=+NoYesYesNo

2021/4/277Hypothesis2Surgicalventricularreconstruction(SVR)combinedwithCABGandevidence-basedmedicaltherapy(MED)decreasesdeathorcardiachospitalizationcomparedtoCABGandMEDwithoutSVR.90%powerfor20%reductionassuming≥45%3-yeareventrateallowingfor20%treatmentcrossovers.7%ofCABGand9%ofCABG+SVRpatientsdidnotreceiveassignedoperation.Follow-up99%completeovermedianof48months.Alloutcomesreportedbyoperationassignedbyrandomization.Conductofoperationreportedbyprocedurereceived.BaselineClinicalCharacteristicsCharacteristicCABGN=499CABG+SVRN=501Age,median25th,75th,years62(54,66)62(56,69)Female78(16%)69(14%)White90%92%Diabetes35%34%Creatinine,>0.5mg/dL8%9%Priorstroke6%6%MitralRegurgitationbyTreatmentin1,000

Hypothesis2PatientsMitralRegurgitationSeverityCABGN=499CABG+SVRN=501Noneortrace173(35%)190(38%)Mild(≤2+)233(47%)216(44%)Moderate(3+)72(15%)70(14%)Severe(4+)16(3%)20(4%)Notassessed5(4%)5(3%)18%SiteReportedLeftVentricularFunctionfor

1,000Hypothesis2PatientsbyTreatmentLVFunctionCABGN=499CABG+SVRN=501SiteQualifyingStudy

Echocardiogram(%)66%63%

Contrastventriculogram13%18%

CMR11%9%

GatedSPECT10%10%LVEF,median(25th,75th).28(.23,.31).28(.24,.31)ESVI,median(25th,75th),mL/m282(65,102)82(66,105)%anteriorwallwithakinesia/dyskinesia,median(25th,75th)56(40,60)50(40,60)CoronaryAnatomybyTreatmentfor

1,000Hypothesis2PatientsMajorCoronaryArterieswithStenosis%StenosisCABGN=499CABG+SVRN=501One≥50%7%10%LMstenosis50-74%14%12%One≥75%17%20%Two≥75%41%42%Three≥75%41%36%ProximalLAD≥75%78%74%LMstenosis≥75%6%7%Dukecoronarydiseaseindex*Median(25th,75th)65(43,91)65(39,91)*0=coronaryangiogramshowsnocoronarydisease,100=≥95%LMstenosisMedicationatBaselineMedicationCABGN=499CABG+SVRN=501Betablocker85%87%ACEinhibitororangiotensinreceptorblocker87%89%ACEinhibitor80%82%Digoxin17%14%Diuretic69%66%Aspirin77%77%Aspirinorwarfarin81%83%Statin79%75%OperativeConductbyOperationReceived

in979Hypothesis2PatientsVariableCABGN=490CABG+SVRN=489PStatusatOperation

Electiveoperation84%83%0.54

Urgent13%13%

Emergency3%4%BypassGrafts0.34

1ormorearterialgrafts93%89%

2orlesstotalgrafts27%30%

3ormoretotalgrafts73%70%Mitralsurgery17%19%0.50SVRpatch59%EfficiencyofOperativeCare

in979Hypothesis2PatientsDurationofOperationCABGN=490CABG+SVRN=489PTotaltimeinoperatingroom(median,25th,75th),hours4.9(4.1,6.0)5.5(4.7,6.6)<0.001Cardiopulmonarybypasstime(median,25th,75th),minutes99(73,125)124(99,158)<0.001Aorticocclusion(median,25th,75th),minutes62(45,84)80(62,106)<0.001RequirementsforPostoperativeCare

Endotrachealintubation(median,25th,75th),hours15.1(10.9,22.1)16.6(12.0,25.2)0.002

Acutecare(median,25th,75th),hours49.8(28.8,95.5)69.5(42,137)<0.001Hospitalization>30days22(5%)31(6%)0.20BaselineandFourMonthEnd-SystolicVolumeIndex(ESVI)in373Hypothesis2PatientsWithQuantitativeEchocardiogramatBothIntervalsESVI82ml/m277ml/m283ml/m267ml/m2P<0.001CanadianCardiovascularSocietyAnginaClassinHypothesis2PatientsatBaselineandLatestFollow-upPatientsNoAngina

121ClassI-II

130ClassIII-IV

248NoAngina

339ClassI-II

88ClassIII-IV

8NoAngina

128ClassI-II

129ClassIII-IV

244NoAngina

339ClassI-II

83ClassIII-IV

6Anginasymptomsimprovedbyanaverageof1.7classesinbothcohorts(P=0.84).NewYorkHeartAssociationHeartFailureClassinHypothesis2PatientsatBaselineandLatestFollow-upPatientsClassI36ClassII

222ClassIII-IV

241ClassI

165ClassII

190ClassIII-IV

80ClassI50ClassII

207ClassIII-IV

244ClassI

179ClassII

188ClassIII-IV

62HeartfailuresymptomsimprovedbyanaverageofoneclassInbothcohorts(P=0.70).BaselineandFourMonth6-MinuteWalkin693Hypothesis2PatientswithBaselineAssessmentPatients30-DayMortalityOutcomeCABGN=499CABG+SVRN=501PDeathWithin30DaysAfterRandomization

Allpatientsbyintentiontotreat22/499(4.4%)30/501(6.0%)0.26DeathDuringorWithin30DaysofOperation

Operatedpatientsbyintentiontotreat25/490(5.1%)26/489(5.3%)0.88

Operatedpatientsbyoperationreceived23/498(4.6%)28/481(5.8%)0.4000.10.20.30.40.50.60.7012345EventRateYearsfromRandomizationCABG49950131931927027522021699112323CABGCABG+SVRNo.atRisk

DeathorCardiacHospitalization

Kaplan-MeierEstimatesofPrimaryEndpoint292events00.10.20.30.40.50.60.7012345EventRateYearsfromRandomizationCABGCABG+SVRHR0.99(95%CI:0.84,1.17),P=0.90

49950131931927027522021699112323CABGCABG+SVRNo.atRisk

DeathorCardiacHospitalization

Kaplan-MeierEstimatesofPrimaryEndpoint

292events289events

Mortality(All-Cause)

Kaplan-MeierEstimates00.10.20.30.40.50.60.7012345MortalityRateYearsfromRandomizationCABG4995014344294174043633522011935953CABGCABG+SVRNo.atRisk141deaths

Mortality(All-Cause)

Kaplan-MeierEstimates00.10.20.30.40.50.60.7012345MortalityRateYearsfromRandomizationCABG+SVRHR1.00(95%CI:0.79,1.26),P=0.98

4995014344294174043633522011935953CABGCABG+SVRNo.atRisk141deaths138deathsCABGSummaryofOutcomesinSTICHH2OutcomesCABGN=499CABG+SVRN=501HazardRatio95%CIPDeathorcardiachospitalization292(59%)289(58%)0.99(0.84,1.17)0.90Death141(28%)138(28%)1.00(0.79,1.26)0.98Hospitalization(cardiac)211(42%)204(41%)0.97(0.80,1.18)0.73Hospitalization(allcause)272(55%)268(53%)0.98(0.83,1.16)0.82AcuteMI22(4%)20(4%)1.01(0.54,1.87)0.96Stroke31(6%)23(5%)0.77(0.45,1.32)0.35HazardRatios,ConfidenceIntervals,andTestsforInteractionSubgroup N HR(95%CI) PValueAllSubjects 1000 0.99(0.84,1.17) Age 0.48≥65 391 1.06(0.83,1.35) <65 609 0.94(0.76,1.17) Gender 0.60Male 853 1.01(0.84,1.20) Female 147 0.90(0.58,1.39) Race 0.44Minority 124 0.83(0.51,1.36) Non-minority 876 1.01(0.85,1.20) CurrentNYHAHFclass 0.97IorII 515 0.99(0.78,1.25) IIIorIV 485 0.99(0.79,1.24) Subgroup N HR(95%CI) PValueCCSanginaclass 0.39≤ClassII 508 0.92(0.73,1.16) ClassIIIorIV 492 1.06(0.85,1.34) Baselinediabetes 0.20Yes 344 1.14(0.87,1.50) No 656 0.92(0.75,1.12) LVEF(sitereported) 0.33≤28 534 1.07(0.86,1.31) >28 466 0.90(0.70,1.17) #ofdiseasedvessels≥50% 0.211or2 362 0.87(0.65,1.13) 3 638 1.07(0.87,1.31) Leftmain≥50%orproximalLAD≥75% 0.53No 179 0.89(0.61,1.30) Yes 821 1.02(0.85,1.22) Subgroup N HR(95%CI) PValueMitralregurgitation 0.44Noneortrace 363 0.89(0.68,1.17) Mild(≤2+) 449 1.12(0.88,1.43) Mod.orsevere 178 0