外科治疗缺血性心力衰竭STICH的研究课件

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的研究外科治疗缺血性心力衰竭STICH Financial DisclosuresSTICH Financial DisclosuresOriginal Recipient InstitutionOriginal Recipient InstitutionPrincipal InvestigatorPrincipal InvestigatorActivityActivityDuke University Medical CenterDuke University Medical CenterRobert H.JonesRobert H.JonesClinical Coordinating CtrClinical Coordinating CtrDuke University Medical CenterDuke University Medical CenterKerry L.LeeKerry L.LeeStatistical and Data CCStatistical and Data CCDuke University Medical CenterDuke University Medical CenterDaniel B.MarkDaniel B.MarkEQOL Core LaboratoryEQOL Core LaboratoryUniv of Alabama-BirminghamUniv of Alabama-BirminghamGerald M.PohostGerald M.PohostCMR Core LaboratoryCMR Core LaboratoryMayo ClinicMayo ClinicJae K.OhJae K.OhECHO Core LaboratoryECHO Core LaboratoryUniversity of PittsburghUniversity of PittsburghArthur M.FeldmanArthur M.FeldmanNCG Core LaboratoryNCG Core LaboratoryNorthwestern UniversityNorthwestern UniversityRobert O.BonowRobert O.BonowRN Core LaboratoryRN Core LaboratoryWashington Hospital CenterWashington Hospital CenterJulio A.PanzaJulio A.PanzaDECIPHER SubstudyDECIPHER SubstudyBaylor University Medical CtrBaylor University Medical CtrPaul GrayburnPaul GrayburnMR TEE SubstudyMR TEE SubstudyFunding Sources:Funding Sources:National Heart,Lung and Blood Institute 97.3%National Heart,Lung and Blood Institute 97.3%Chase Medical 0.3%Chase Medical 0.3%Abbott Laboratories 2.3%Abbott Laboratories 2.3%CV Therapeutics 0.1%CV Therapeutics 0.1%STICH Financial DisclosuresOriCore STICH Study Organizationn nPrincipal Investigator:Robert H JonesPrincipal Investigator:Robert H Jonesn nCo-Principal investigator:Eric VelazquezCo-Principal investigator:Eric Velazquezn nDCC Principal Investigator:Kerry L LeeDCC Principal Investigator:Kerry L Leen nStudy Chair:Jean L RouleauStudy Chair:Jean L Rouleaun nExecutive Committee:Robert H Jones,Eric Velazquez,Kerry L Executive Committee:Robert H Jones,Eric Velazquez,Kerry L Lee,Jean L Rouleau,Patrice Desvigne-Nickens,George Sopko,Lee,Jean L Rouleau,Patrice Desvigne-Nickens,George Sopko,Chris OConnor,Robert Michler,and Jae Oh.Chris OConnor,Robert Michler,and Jae Oh.n nDSMB chair:Sid GoldsteinDSMB chair:Sid Goldsteinn nPublications Committee chair:James HillPublications Committee chair:James Hilln nClinical Endpoints Committee:Peter CarsonClinical Endpoints Committee:Peter CarsonCore STICH Study OrganizationPHypothesis 2 Enrollment by CountryHypothesis 2 Enrollment by Country 1000 patients1000 patients 96 clinical sites96 clinical sites 23 countries23 countries 1231 days1231 daysHypothesis 2 Enrollment by CouRandomized PatientsRandomized PatientsNumbers for AnalysisNumbers for Analysisby Hypothesisby HypothesisMED+CABG(610)MED+CABG(499)CAD,EF CAD,EF 0.35 0.35Eligible for MED-only treatment?Eligible for MED-only treatment?Eligible for SVR?Eligible for SVR?Not in trialNot in trialNoNoHypothesis 1Hypothesis 1n=1212n=1212Hypothesis 2Hypothesis 2n=1000n=1000MED(602)MED+CABG+SVR(501)Stratum An=10611MED(527)2MED+CABG(534)Eligible for Eligible for SVR?SVR?Stratum Cn=859YesYes6MED+CABG(423)7MED+CABG+SVR(436)Stratum Bn=2163MED(75)5MED+CABG+SVR(65)4MED+CABG(76)+21362136Randomized ptsRandomized pts=+602602MED onlyMED only10331033CABG addedCABG added 501 501CABG+SVR addedCABG+SVR added=+NoNoYesYesYesYesNoNo Randomized PatientsNumbers for外科治疗缺血性心力衰竭STICH的研究课件2020/11/472020/11/47Hypothesis 2n nSurgical ventricular reconstruction(SVR)combined with Surgical ventricular reconstruction(SVR)combined with CABG and evidence-based medical therapy(MED)CABG and evidence-based medical therapy(MED)decreases death or cardiac hospitalization compared to decreases death or cardiac hospitalization compared to CABG and MED without SVR.CABG and MED without SVR.n n90%power for 20%reduction assuming 45%3-year event 90%power for 20%reduction assuming 45%3-year event rate allowing for 20%treatment crossovers.rate allowing for 20%treatment crossovers.n n7%of CABG and 9%of CABG+SVR patients did not 7%of CABG and 9%of CABG+SVR patients did not receive assigned operation.receive assigned operation.n nFollow-up 99%complete over median of 48 months.Follow-up 99%complete over median of 48 months.n nAll outcomes reported by operation assigned by All outcomes reported by operation assigned by randomization.randomization.n nConduct of operation reported by procedure receivedConduct of operation reported by procedure received.Hypothesis 2Surgical ventriculBaseline Clinical CharacteristicsCharacteristicCharacteristicCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501Age,median 25Age,median 25thth,75,75thth,years,years62(54,66)62(54,66)62(56,69)62(56,69)FemaleFemale78(16%)78(16%)69(14%)69(14%)WhiteWhite90%90%92%92%DiabetesDiabetes35%35%34%34%Creatinine,0.5 mg/dLCreatinine,0.5 mg/dL8%8%9%9%Prior strokePrior stroke6%6%6%6%Baseline Clinical CharacteristMitral Regurgitation by Treatment in 1,000 Mitral Regurgitation by Treatment in 1,000 Hypothesis 2 PatientsHypothesis 2 PatientsMitral Regurgitation Mitral Regurgitation SeveritySeverityCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501None or traceNone or trace173(35%)173(35%)190(38%)190(38%)Mild(2+)Mild(2+)233(47%)233(47%)216(44%)216(44%)Moderate(3+)Moderate(3+)72(15%)72(15%)70(14%)70(14%)Severe(4+)Severe(4+)16(3%)16(3%)20(4%)20(4%)Not assessedNot assessed5(4%)5(4%)5(3%)5(3%)18%18%18%Mitral Regurgitation by TreatmSite Reported Left Ventricular Function for Site Reported Left Ventricular Function for 1,000 Hypothesis 2 Patients by Treatment1,000 Hypothesis 2 Patients by TreatmentLV FunctionLV FunctionCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501Site Qualifying StudySite Qualifying Study Echocardiogram(%)Echocardiogram(%)66%66%63%63%Contrast ventriculogramContrast ventriculogram13%13%18%18%CMRCMR11%11%9%9%Gated SPECTGated SPECT10%10%10%10%LVEF,median(25th,75th)LVEF,median(25th,75th).28(.23,.31).28(.23,.31).28(.24,.31).28(.24,.31)ESVI,median(25th,75th),mL/mESVI,median(25th,75th),mL/m2 282(65,102)82(65,102)82(66,105)82(66,105)%anterior wall with akinesia/%anterior wall with akinesia/dyskinesia,median(25dyskinesia,median(25thth,75,75thth)56(40,60)56(40,60)50(40,60)50(40,60)Site Reported Left VentricularCoronary Anatomy by Treatment for Coronary Anatomy by Treatment for 1,000 Hypothesis 2 Patients1,000 Hypothesis 2 PatientsMajor Coronary Major Coronary Arteries with Arteries with StenosisStenosis%Stenosis%StenosisCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501OneOne 50%50%7%7%10%10%LM stenosisLM stenosis50-74%50-74%14%14%12%12%OneOne 75%75%17%17%20%20%TwoTwo 75%75%41%41%42%42%ThreeThree 75%75%41%41%36%36%Proximal LADProximal LAD 75%75%78%78%74%74%LM stenosisLM stenosis 75%75%6%6%7%7%Duke coronary Duke coronary disease index*disease index*MedianMedian(25(25thth,75,75thth)65(43,91)65(43,91)65(39,91)65(39,91)*0=coronary angiogram shows no coronary disease,100=95%LM stenosis0=coronary angiogram shows no coronary disease,100=95%LM stenosis0=coronary angiogram shows no coronary disease,100=95%LM stenosisCoronary Anatomy by Treatment Medication at BaselineMedicationMedicationCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501Beta blockerBeta blocker85%85%87%87%ACE inhibitor or angiotensin ACE inhibitor or angiotensin receptor blockerreceptor blocker87%87%89%89%ACE inhibitorACE inhibitor80%80%82%82%DigoxinDigoxin17%17%14%14%DiureticDiuretic69%69%66%66%AspirinAspirin77%77%77%77%Aspirin or warfarinAspirin or warfarin81%81%83%83%StatinStatin79%79%75%75%Medication at BaselineMedicatiOperative Conduct by Operation Received Operative Conduct by Operation Received in 979 Hypothesis 2 Patientsin 979 Hypothesis 2 PatientsVariableVariableCABGCABGN=490N=490CABG+SVRCABG+SVRN=489N=489P PStatus at OperationStatus at Operation Elective operationElective operation84%84%83%83%0.540.54 UrgentUrgent13%13%13%13%EmergencyEmergency3%3%4%4%Bypass GraftsBypass Grafts0.340.34 1 or more arterial grafts1 or more arterial grafts93%93%89%89%2 or less total grafts2 or less total grafts27%27%30%30%3 or more total grafts3 or more total grafts73%73%70%70%Mitral surgeryMitral surgery17%17%19%19%0.500.50SVR patchSVR patch59%59%Operative Conduct by OperationEfficiency of Operative Care Efficiency of Operative Care in 979 Hypothesis 2 Patientsin 979 Hypothesis 2 PatientsDuration of OperationDuration of OperationCABGCABGN=490N=490CABG+SVRCABG+SVRN=489N=489P PTotal time in operating room Total time in operating room(median,25(median,25thth,75,75thth),hours),hours4.9(4.1,6.0)4.9(4.1,6.0)5.5(4.7,6.6)5.5(4.7,6.6)0.0010.001Cardiopulmonary bypass timeCardiopulmonary bypass time(median,25(median,25thth,75,75thth),minutes),minutes99(73,125)99(73,125)124(99,158)124(99,158)0.0010.001Aortic occlusion(median,25Aortic occlusion(median,25thth,7575thth),minutes),minutes62(45,84)62(45,84)80(62,106)80(62,106)0.0010.001Requirements for Postoperative CareRequirements for Postoperative Care Endotracheal intubationEndotracheal intubation (median,25 (median,25thth,75,75thth),hours),hours15.1(10.9,22.1)15.1(10.9,22.1)16.6(12.0,25.2)16.6(12.0,25.2)0.0020.002 Acute care(median,25Acute care(median,25thth,75 75thth),hours),hours49.8(28.8,95.5)49.8(28.8,95.5)69.5(42,137)69.5(42,137)0.00130 daysHospitalization 30 days22(5%)22(5%)31(6%)31(6%)0.200.20Efficiency of Operative Care Baseline and Four Month End-Systolic Volume Baseline and Four Month End-Systolic Volume Index(ESVI)in 373 Hypothesis 2 Patients With Index(ESVI)in 373 Hypothesis 2 Patients With Quantitative Echocardiogram at Both IntervalsQuantitative Echocardiogram at Both IntervalsESVI82 ml/m277 ml/m283 ml/m267 ml/m2P0.001P0.001P0.001Baseline and Four Month End-SyCanadian Cardiovascular Society Angina Class in Canadian Cardiovascular Society Angina Class in Hypothesis 2 Patients at Baseline and Latest Follow-upHypothesis 2 Patients at Baseline and Latest Follow-upPatientsNo Angina121Class I-II130Class III-IV248No Angina339Class I-II88Class III-IV8No Angina128Class I-II129Class III-IV244No Angina339Class I-II83Class III-IV6Angina symptoms improved by an average of 1.7 classes Angina symptoms improved by an average of 1.7 classes in both cohorts(P=0.84).in both cohorts(P=0.84).Canadian Cardiovascular SocietNew York Heart Association Heart Failure Class in New York Heart Association Heart Failure Class in Hypothesis 2 Patients at Baseline and Latest Follow-upHypothesis 2 Patients at Baseline and Latest Follow-upPatientsClass I 36Class II222Class III-IV241Class I165Class II190Class III-IV80Class I 50Class II207Class III-IV244Class I179Class II188Class III-IV62Heart failure symptoms improved by an average of one classHeart failure symptoms improved by an average of one classIn both cohorts(P=0.70).In both cohorts(P=0.70).New York Heart Association HeaBaseline and Four Month 6-Minute Walk in 693 Baseline and Four Month 6-Minute Walk in 693 Hypothesis 2 Patients with Baseline AssessmentHypothesis 2 Patients with Baseline AssessmentPatientsBaseline and Four Month 6-Minu30-Day Mortality30-Day MortalityOutcomeOutcomeCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501P PDeath Within 30 Days After RandomizationDeath Within 30 Days After Randomization All patients by intentionAll patients by intention to treat to treat22/499(4.4%)22/499(4.4%)30/501(6.0%)30/501(6.0%)0.260.26Death During or Within 30 Days of OperationDeath During or Within 30 Days of Operation Operated patients byOperated patients by intention to treat intention to treat25/490(5.1%)25/490(5.1%)26/489(5.3%)26/489(5.3%)0.880.88 Operated patients by Operated patients by operation received operation received23/498(4.6%)23/498(4.6%)28/481(5.8%)28/481(5.8%)0.400.4030-Day MortalityOutcomeCABGCAB00.10.20.30.40.50.60.7012345Event RateYears from RandomizationCABG49950131931927027522021699112323CABGCABG+SVRNo.at Risk Death or Cardiac Hospitalization Death or Cardiac Hospitalization Kaplan-Meier Estimates of Primary Endpoint Kaplan-Meier Estimates of Primary Endpoint292 events00.10.20.30.40.50.60.7012345Ev00.10.20.30.40.50.60.7012345Event RateYears from RandomizationCABGCABG+SVRHR 0.99(95%CI:0.84,1.17),P=0.90 49950131931927027522021699112323CABGCABG+SVRNo.at Risk Death or Cardiac HospitalizationDeath or Cardiac Hospitalization Kaplan-Meier Estimates of Primary Endpoint Kaplan-Meier Estimates of Primary Endpoint 292 events289 events 00.10.20.30.40.50.60.7012345Ev Mortality(All-Cause)Mortality(All-Cause)Kaplan-Meier Estimates Kaplan-Meier Estimates00.10.20.30.40.50.60.7012345Mortality RateYears from RandomizationCABG4995014344294174043633522011935953CABGCABG+SVRNo.at Risk141 deaths Mortality(All-Mortality(All-Cause)Mortality(All-Cause)Kaplan-Meier Estimates Kaplan-Meier Estimates00.10.20.30.40.50.60.7012345Mortality RateYears from RandomizationCABG+SVRHR 1.00(95%CI:0.79,1.26),P=0.98 4995014344294174043633522011935953CABGCABG+SVRNo.at Risk141 deaths 138 deathsCABG Mortality(All-Summary of Outcomes in STICH H2OutcomesOutcomesCABGCABGN=499N=499CABG+SVRCABG+SVRN=501N=501Hazard RatioHazard Ratio95%CI95%CIP PDeath or cardiac Death or cardiac hospitalizationhospitalization292(59%)292(59%)289(58%)289(58%)0.99(0.84,1.17)0.99(0.84,1.17)0.900.90DeathDeath141(28%)141(28%)138(28%)138(28%)1.00(0.79,1.26)1.00(0.79,1.26)0.980.98Hospitalization Hospitalization(cardiac)(cardiac)211(42%)211(42%)204(41%)204(41%)0.97(0.80,1.18)0.97(0.80,1.18)0.730.73Hospitalization Hospitalization(all cause)(all cause)272(55%)272(55%)268(53%)268(53%)0.98(0.83,1.16)0.98(0.83,1.16)0.820.82Acute MIAcute MI22(4%)22(4%)20(4%)20(4%)1.01(0.54,1.87)1.01(0.54,1.87)0.960.96StrokeStroke31(6%)31(6%)23(5%)23(5%)0.77(0.45,1.32)0.77(0.45,1.32)0.350.35Summary of Outcomes in STICH HHazard Ratios,Confidence Intervals,and Tests for InteractionHazard Ratios,Confidence Intervals,and Tests for InteractionSubgroupNHR(95%CI)P ValueAll Subjects10000.99(0.84,1.17)Age0.48 653911.06(0.83,1.35)284660.90(0.70,1.17)#of diseased vessels 50%0.21 1 or 23620.87(0.65,1.13)36381.07(0.87,1.31)Left main 50%or proximal LAD 75%0.53 No1790.89(0.61,1.30)Yes8211.02(0.85,1.22)SubgroupN HR(95%CI)P ValueSubgroupNHR(95%CI)P ValueMitral regurgitation 0.44 None or trace3630.89(0.68,1.17)Mild(2+)4491.12(0.88,1.43)Mod.or severe 1780.94(0.65,1.36)Stratum0.44 B1411.15(0.76,1.76)C8590.96(0.81,1.15)Region0.41 Poland2881.02(0.76,1.37)USA2001.10(0.79,1.54)Canada1540.77(0.50,1.18)West Europe1640.80(0.53,1.22)Other1941.24(0.81,1.91)SubgroupN HR(95%CI)P ValueConclusionsn nThe STICH trial definitively shows adding SVR to CABG The STICH trial definitively shows adding SVR to CABG provides no clinical benefit beyond that of CABG alone in provides no clinical benefit beyond that of CABG alone in the study population.the study population.n nBoth operative strategies provided similar short-and long-Both operative strategies provided similar short-and long-term relief of angina and HF and improvement in 6-minute term relief of angina and HF and improvement in 6-minute walk test performance.walk test performance.n nSVR added to CABG decreased LV size significantly more SVR added to CABG decreased LV size significantly more than CABG alone and confirms the anatomic change than CABG alone and confirms the anatomic change reported in prior SVR studies.reported in prior SVR studies.n nFurther analyses of STICH Hypothesis 2 data may identify Further analyses of STICH Hypothesis 2 data may identify patient characteristics associated with benefit or harm patient characteristics associated with benefit or harm from adding SVR to CABG.from adding SVR to CABG.ConclusionsThe STICH trial def谢谢谢谢