【医学课件】scd-heft研究,prove-it研究和synergy研究ppt课件.ppt

ACC2004:SCD-HeFT,PROVE-IT,andSYNERGYunderdebate,EricJTopolMDProvostandChiefAcademicOfficerChairman,DepartmentofCardiovascularMedicineClevelandClinicFoundationCleveland,OHRobertMCaliffMDProfessorofMedicineAssociateViceChancellorforClinicalResearchDirector,DukeClinicalResearchInstituteDukeUniversityMedicalCenterDurham,NC,天马行空官方博客：,SCD-HEFTSuddenCardiacDeathinHeartFailureTrialPROVE-ITPravastatinorAtorvastatinEvaluationandInfectionTherapySYNERGYSuperiorYieldoftheNewStrategyofEnoxaparin,Revascularization,andGlycoproteinIIb/IIIaInhibitors,Topics,SuddenCardiacDeathinHeartFailureTrialSCD-HeFT,Background,DrGustBardy(SeattleInstituteforCardiacResearch,WA)andcolleagues:Dodefibrillatorssavelives?Wouldtheybeusefulinthemoregeneralpopulationofpatientswithheartfailure?,SCD-HeFT,Design,SCD-HeFT,2521patientswithNYHAclass2-3HFandLVEF35%148centersinNorthAmericaandNewZealandLargestinternal-cardioverter-defibrillator(ICD)trialeverconductedICDvsplaceboMedianfollow-upof45months,Publicandprivatelysponsored:MedtronicInc(Minneapolis,MN)WyethPharmaceuticals(Madison,NJ)TheNationalHeart,Lung,andBloodInstitute(Bethesda,MD),Funding,SCD-HeFT,ICDpatients,SCD-HeFT,All-causemortality,SCD-HeFT,Relativeriskforall-causemortality,SCD-HeFT,Relativeriskforall-causemortality,SCD-HeFT,Standardmedicaltherapy,SCD-HeFT,Oneofthemostimpressivetrialsinsuddencardiacdeathsanddefibrillators.WhatIthoughtaboutthistrial,whichwassoextraordinary,isthatitreallywidenedthefieldofbenefitinthepopulationextendingittothenonischemics.,Impressivetrial,SCD-HeFT,Topol,ThelesssymptomaticpatientsgettingthegreatestbenefitreallyraisesadifficultquestionofwhetherweshouldgoouttheresearchingforpeoplewithasymptomaticLVdysfunctionandputdefibrillatorsinthem.,Difficultquestion,SCD-HeFT,Califf,CallformoreICDs,AsIlookatit,wehaveseveralmillionpeopleouttherewhoshouldhavedefibrillatorsputintomorrow.CaliffThisistheultimatecollisionofevidence-basedmedicineandtheresourcestosupportthat.Topol,SCD-HeFT,Thumbs,Theonlyhole,Ithought,wastheacronym.Imreallyimpressedwiththistrial,ifIhadthreethumbs,Idgiveitthat.Thisisfirst-ratework.,Topol,SCD-HeFT,PravastatinorAtorvastatinEvaluationandInfectionTherapyPROVE-IT,Design,Intensiveandmoderatelipidloweringwithstatintherapyafteracutecoronarysyndrome(ACS)(NEnglJMed2004;350:publishedMarch8,2004)4162patientswithACS(10days)Pravastatin(40mgdaily)vsatorvastatin(80mgdaily)Primaryendpoint:acompositeofall-causemortality,MI,unstableanginarequiringhospitalization,revascularization,andstrokeTwo-yearfollow-up,PROVE-IT,Results,NEnglJMed2004;350,16%reductioninriskfavoringatorvastatin,PROVE-IT,Results,NEnglJMed2004;350,28%reductioninriskfavoringatorvastatin,PROVE-IT,Earlybenefit,Eventcurvesbegantoseparateasearlyas30daysInotherplacebo-controlledstudies4S,HeartProtectionStudytherewasalagofapproximately12to18monthsbeforeeventcurvesseparated,PROVE-IT,LDLreduction,NEnglJMed2004;350,PROVE-IT,Thumbsup,but,Twothumbsup,butwithregrets.Landmarktrial:Evendrugsinthesameclassrequirehead-to-headcomparisonsNeedincentivesforcompaniesthatconductsuchtrialstoberewardedinsteadofpunished,Califf,PROVE-IT,Underpowered,Idonthaveaproblemwiththeresultofthestudy,eventhoughitwasunderpoweredtobeginwith.CaliffTheydidhaveenougheventstoshowadifference.Topol,PROVE-IT,Whatdotheresultsmean?,Ilookedatthistrialwithinterest,beingastatintakermyself.Ifadrugwinshead-to-head,eveninanACSpopulation,thenhigh-doseatorvastatinwouldbethedrugofchoicerightnowNeedforfurtherstudyagainstotherstatinsandcombinations,Califf,PROVE-IT,PROVE-ITandREVERSAL?,REVERSALIVUSstudyshowedalackofatheroscleroticprogressioninstablecoronarypatientsJAMA2004;291:1071-1080BenefitbroaderthanACSUntilprovenotherwise,thiswouldbeanappropriatestartingdoseinsomeonewhocarriessignificantrisk.,PROVE-IT,Topol,AllabouttheLDL?,DoesthePROVE-ITtrialprovethatitsallabouttheLDL?Whataboutrosuvastatin?BiggerLDLbangforyourbuck?Statin/ezetimibecombination?ItisntalljustLDL.Topol,PROVE-IT,LDL-centricworld,REVERSALCRPimportanttolackofatheroscleroticprogressionHowlowtogowithLDL?IfLDLwas80mg/dLandCRPwasquitelow,IdontknowifIwouldkeeptryingtolowerLDLTopol,PROVE-IT,Outcomedata,NeedformoreoutcomedataItsclearwewanttobemoreaggressive,buttoomanyunknownswithotherstatinsanddosesTopolThetwostatinsthatareinplayfrommyperspectivearesimvastatinandatorvastatinCaliff,PROVE-IT,Moretrials,ComingsoonTNTAtorvastatin80mgvsatorvastatin10mgIDEALAtorvastatin80mgvssimvastatin20mgSEARCHLow-dosevshigh-dosesimvastatin,PROVE-IT,Thumbs,Igivethisonetwothumbsup,butwithregrets.Give25%ofPfizersprofitstoBMSforhavingdonetherightthingAfteryearsofthrashingatorvastatinfornothavingdata,theyvegotthedataandImreadytomaketheswitch.,PROVE-IT,Califf,SuperiorYieldoftheNewStrategyofEnoxaparin,Revascularization,andGlycoproteinIIb/IIIaInhibitorsSYNERGY,Background,Millionsoftimesayear,doctorsfromaroundtheworldaremakingdecisionsinacutecoronarysyndromesaboutwhethertouse:UnfractionatedheparinorLow-molecular-weightheparin,SYNERGY,ESSENCE,TIMI11bEnoxaparinappearedhopefulintermsofeasyuse,littlebleedingManypatientsdidnotundergointerventionorreceiveIIb/IIIainhibitorsSYNERGYHigh-riskpopulationwithnon-ST-segmentelevationMI,Enoxaparininpaststudies,SYNERGY,Design,Enoxaparinvsunfractionatedheparin10000high-riskACSpatientsin467centersAged60yearsorolder,positivetroponin,orSTsegmentshiftPrimaryendpointofdeath/MIat30days,SYNERGY,Results,SYNERGY,Bleeding,HICH=intracranialhemorrhage,SYNERGY,Nopriortreatment,SYNERGY,Thumbsup/ThumbsdownApril2004,Conclusion,Intheend,wereleftwithatrialthatbyintentiontotreatshowednoninferiorityforefficacyandamodestexcessofbleeding.,SYNERGY,Califf,Thequestionwasright,thedesignwas