药物对心脏性猝死SCD的预防作用.ppt

TheRoleofDrugsinPreventionofSuddenCardiacDeathWeiminLiProfessorofMedicineCardiovascularDepartment,theFirstClinicalHospital,HarbinMedicalUniversity，Harbin,PresentationOverview,SuddenCardiacDeathEpidemiology,etiology,pathophysiologyOverviewofICDtherapytopreventSCDRolesofDrugsinSCDPreventionSummaryandconclusions,EpidemiologyofSCD,Accountsfor63%ofallcardiacrelateddeathsintheUS.Oneofthemostcommoncausesofdeathindevelopedcountries:,MMWR.Vol51(6)Feb.15,2002.MyerbergRJ,CatellanosA.CardiacArrestandSuddenCardiacDeath.In:BraunwaldE,ed.HeartDisease:ATextbookofCardiovascularMedicine.5thEd.NewYork:WBSaunders.1997:742-779.ZhengZ.Circulation.2001;104:2158-2163.Vreede-SwagemakersJJetal.JAmCollCardiol1997;30:1500-1505.,Geography,MagnitudeofSCDinChina,0.04%,0.1%0.2%,IncidenceofSCDinSpecificPopulations,Adaptedfrom:MyerburgRJ.SuddenCardiacDeath:ExploringtheLimitsofOurKnowledge.JCardiovascElectrophysiolVol.12,pp.369-381,March2001.,300,000,200,000,100,000,AbsolutenumberofSCDPerYear,Multiplerisksubgroups,Patientswithanypreviouscoronaryevent,Patientswithejectionfraction35%orCHF,Cardiacarrest,VT/VFsurvivors,High-riskpost-MIsubgroups,Generaladultpopulation,30,25,20,10,5,0,IncidenceofSCD(%ofgroup),MADITIISCD-HeFT,AVID,CASH,CIDS,MADIT,MUSTT,Suddendeathwasthefirstmanifestationofcoronaryheartdiseasein50%ofmenand63%ofwomen.CHDaccountsforatleast80%ofsuddencardiacdeathsinWesterncultures.,DiseaseCauseofSCD,AmericanHeartAssociation.HeartDiseaseandStrokeStatistics2003Update.Dallas,Tex.:AmericanHeartAssociation;2002.AdaptedfromHeikkietal.NEnglJMed,Vol.345,No.20,2001.MyerbergRJ.HeartDisease,ATextbookofCardiovascularMedicine.6thed.P.895.,ArrhythmicCauseofSCD,AlbertCM.Circulation.2003;107:2096-2101.,12%OtherCardiacCause,88%ArrhythmicCause,Bradycardia16.5%,VF62.4%,PrimaryVT8.3%,TorsadesdePointes12.7%,BaysdeLunaA.AmHeartJ.1989;117:151-159.,ApplicationofICDinChina,200,544,000,“Eventhewealthiestnationscannotaffordtopaytouseeverymedicaladvanceinanypatientwhomightbenefit.”,ThomasBigger,Lancet,2001,RolesofDrugsinSCDPrevention,RolesofDrugsinSCDPrevention,ValueofAntiarrhythmicDrugsClassIantiarrhythmicsBetaBlockersAmiodaroneSotalolValueofNon-antiarrhythmicDrugsElectrolytesACEinhibitors,ARBsandaldosteroneblockersAntithromboticandantiplateletagentsStatinsn-3Fattyacids,SCDPreventionbyAntiarrhythmicDrugs,All-causemortality,Daysafterrandomization,0,50,100,150,200,250,300,350,400,450,500,85,90,95,100,Survival,(%),Placebo(n=725),Encainideorflecainide(n=730),:406,CASTInvestigators.,NEnglJMed,1989;,321,12.,P=0.0003,80,RolesofClassIantiarrhythmicsinSCDPrevention,CAST:CardiacArrhythmiaSuppressionTrial,CASTII:CardiacArrhythmiaSuppressionTrialII,AswiththeantiarrhythmicagentsusedinCAST-I,theuseofmoricizineinCAST-IItosuppressasymptomaticormildlysymptomaticventricularprematuredepolarizationstotrytoreducemortalityaftermyocardialinfarctionisnotonlyineffectivebutalsoharmful.,RolesofBetaBlockersinSCDPrevention,NorwegianMulticentreStudyGroup.NEnglJMed.1981;304:801-807.,OverviewofNorwegianTimololTrialandBHAT(Beta-BlockerHeartAttack)Trial(Post-MILVDpatients),39%Reducedmortality,26%Decreasedmortality,Beta-BlockerHeartAttackTrialResearchGroup.JAMA.1982;247:1707-1714.,BHAT,Norwegian,AverageincidenceofSCDinlongtermtrialscomparingblockerswithplaceboafterMI,NuttallSL,ToescuV,KendallMJ.BMJ.2000;320:581.,CAPRICORN:CarvedilolPost-InfarctSurvivalControlinLVDysfunction-TRIALRESULTS-,DargieHJetal.EurJHeartFail.2000;2:325-332.,CIBISII:CardiacInsufficiencyBisoprololStudyII-RESULTS-,CIBIS-IIInvestigatorsandCommittees.,Lancet,1999;,353,MERIT-HF:MetoprololCR/XLRandomizedInterventionTrialincongestiveHeartFailure-RESULTS-,MERIT-HFStudyGroup.,Lancet,1999;,353,:2001,7.,0,0.5,1.0,1.5,Relativeriskformortality,Relativerisk(95%CI),Mortality,MetoprololCR/XLbetter,Risk,reduction,(%),Totalmortality,Cardiovascularmortality,Suddendeath,Deathfromworsening,heartfailure,34,38,41,49,0.0062,0.00003,0.0002,0.0023,P,COPERNICUS:CarvedilolProspectiveRandomizedCumulativeSurvivaltrial-SUMMARY-,Inpatientswithseverechronicheartfailure,carvedilolinadditiontostandardtherapyreduced:All-causemortalityCombinedendpointofall-causemortalityandhospitalizationforanyreason,PackerM,CoatsAJ,FowlerMBetal.NEnglJMed2001;344:16518.,RolesofBetaBlockersinSCDPrevention,RolesofAmiodaroneinSCDPrevention,ConnollySJ.Meta-analysisofantiarrhythmicdrugtrials.AmJCardiol1999;84:90R3R.,Ameta-analysisofeffectsofamiodaroneonSCD,Meta-analysisofeffectsofamiodaroneonSCD-RESULTS-,Cumulativeriskoftotalmortalityandarrhythmic/suddendeathfromameta-analysisof13trialsofamiodarone,Meta-analysisoftheICDsecondarypreventiontrials,ConnollySJ.etal.Meta-analysisoftheimplantablecardioverterdefibrillatorsecondarypreventiontrialsEuropeanHeartJournal.2000;20712078,Meta-analysisofeffectsofamiodaroneonSCD-RESULTS-,Cumulativeriskoffataleventsortheamiodaroneandtreatmentarms.,Hazardratio:0.73P0.001,Hazardratio:0.49P35%and35%,TheefficacyoftheICDoveramiodaroneappearstobedependentuponthedegreeofleftventriculardysfunction.,Mortality,Folow-up(m),MortalitybyIntention-to-TreatSCD-HeFT-2004,HR97.5%CIPAmiodaronevsplacebo1.060.86,1.300.529ICDtherapyvsplacebo0.770.62,0.960.007,BardyGH,LeeKL,MarkDB,etal.NEnglJMed,2005,352:225,ICD+AADs,PercentArrhythmia-Free,26%reductionineventratethetimetofirsteventextendedmedian1.3monthstomedian4.4months,SteinbergJS,MartinsJ,SadanandanS,etal.AmHeartJ.2001;142:520-529,ICD,ICD+AADs,RolesofSotalolinSCDPrevention,SWORDSurvivalResults,StudystoppedprematurelyinNov.1994duetoincreasedmortalityinpatientpopulationtreatedwithd-sotalol,WaldoAL.Lancet.1996;348:7-12.,RolesofSotalolinSCDPrevention,KuhlkampV.Suppressionofsustainedventriculartachyarrhythmias:acomparisonofd,l-sotalolwithnoantiarrhythmicdrugtreatment.JAmCollCardiol.1999;33:46-52.,ICD/sotalol,sotalol,ICD,RolesofAntiarrhythmicDrugsinSCDPrevention,ValueofAntiarrhythmicDrugsClassIantiarrhythmics:notonlyineffectivebutalsoharmfulBetaBlockers:Effectiveinsuppressingventricularectopicbeatsandarrhythmias;reduceincidenceofSCDAmiodarone:Nodefinitesurvivalbenefit;somestudieshaveshownreductioninSCDinpatientswithLVdysfunction,especiallywhengiveninconjunctionwithBB.butithascomplexdruginteractionsandmanyadversesideeffects.Sotalol:Suppressesventriculararrhythmias;ismorepro-arrhythmicthanamiodarone,nosurvivalbenefitclearlyshownConclusions:Antiarrhythmicdrugs(exceptforBB)shouldnotbeusedasprimarytherapyofthepreventionofSCD.BothsotalolandamiodaronehavebeenshowntoreducethefrequencyofICDshocktherapy,SCDPreventionbyNon-antiarrhythmicDrugs,Rolesofangiotensinconvertingenzymeinhibitors(ACEI)angiotensinreceptorblockers(ARB)andaldosteroneblockerinSCDPrevention,Meta-analysisof15randomizedcontrolledtrial-RESULTS-,DomanskiMJ,ExnerDV,BorkowfCB,etal.JACCVol.33,No.3,1999:598604,Meta-analysisof15randomizedcontrolledtrial-RESULTS-,TheoverallORforSCDinpatientsrandomizedtoACEinhibitortherapywas0.80(95%CI0.70to0.92)ACEIsreducetheriskofSCDabout20%inpost-MIpatients,HOPE:HeartOutcomesPreventionEvaluationstudy-RESULTS-,P,Primaryoutcomeanddeathsfromanycause,Relativerisk,(95%CI),MI,stroke,ordeathfrom,cardiovascularcauses,Deathfromcardiovascularcauses,MI,Stroke,Deathfromnoncardiovascularcauses,Deathfromanycause,0.78(0.70,0.86),0.74(0.64,0.87),0.80(0.70,0.90),0.68(0.56,0.84),1.03(0.85,1.26),0.84(0.75,0.95),0.001,0.001,0.001,0.001,0.74,0.005,RamiprilreducedtheriskofSCDabout38%(0.02),SOLVDTrialRESULTS,NEnglJMed1991;325:293-302,AllCauseMortalityandSCD,SOLVDTreatmentTrial,SOLVDPreventionTrial,10%RiskReductioninSCDp=NS,8%RiskReductioninAllCauseMortalityP=0.30,0,5,10,15,20,25,0,6,12,18,24,30,36,42,48,Months,Mortality(%),7%RiskReductioninSCDp=NS,CHARMCandesartaninHeartfailureAssessmentofReductioninMortalityandmorbidity-RESULTs-,CHARMCandesartaninHeartfailureAssessmentofReductioninSCD-RESULTs-,TheCHARMstudyInvestigators.Circulation.2004;110:2618-26.,TreatmentofheartfailurepatientswithcandesartanresultedinareductioninSCD(p=0.036),RALES:theRandomizedAldactoneEvaluationStudy-RESULTs-,P,Cardiaccauses,Progressionofheartfailure,Suddendeath,0.001,Cardiovasculardeath,Spironolactonegroup,(n=822),314,189,110,15,226,227,82,17,0.69(0.580.82),0.64(0.510.80),Placebogroup,(n=841),Raletiverisk,(95%CI),VARIABLE,Myocardialinfarction,0.71(0.540.95),0.02,0.001,Pitt,NEnglJMed1999;,SCDRiskReduction:29%(p0.02),EPHESUSEplerenonePost-AMIHeartFailureEfficacyandSurvivalStudy-RESULTs-,All-causeMortalityRR0.85p=0.008,Eplerenone,Placebo,NEnglJMed2003;348:1309-21EurJHeartFail.2006;8:295-301,CVDeathRR0.87p=0.002,TreatmentwitheplerenoneinthesubgroupofpatientswithLVEF30%resultedinrelativeriskreductionsof33%forSCD(P=0.008),Rolesofangiotensinconvertingenzymeinhibitors(ACEI)angiotensinreceptorblockers(ARB)andaldosteroneblockerinSCDPrevention,RolesofAntithromboticTherapyinSCDPrevention,DatafromSOLVDpreventionandtreatmenttrials,IncidenceandCrudeRelativeRiskofSuddenCoronaryDeath,CardiovascularDeath,andAll-CauseMortalityAccordingtoAntithromboticTherapy,Neither2252.761.07549.241.085310.451.0Antiplatelet1491.820.664705.750.635346.480.63Anticoagulant401.860.701557.210.821858.560.87Both102.240.81347.610.83378.280.80,95%CIthe2-sided95%confidenceintervalforthepointestimateoftherelativerisk.Cardiovasculardeathsincludesuddencardiacdeath,deathduetoprogressivepumpfailure,fatalmyocardialinfarction,andcerebrovasculardeaths.Therateisexpressedaseventsper100patient-yearsoffollow-up.RRrelativerisk.,SuddenCoronaryDeath,CardiovascularDeath,AllCauseMortality,No.RateRRNo.RateRRNo.RateRR,DriesDL,etal.AmJCardiol.1997;79:909-913,RolesofAntithromboticTherapyinSCDPrevention,AntiplateletandanticoagulantmonotherapyeachremainedindependentlyassociatedwithareductionintheriskofSCD:antiplatelettherapywitha24%reduction.anticoagulanttherapywitha32%reduction.Thus,inpatientswithmoderatetosevereleftventricularsystolicdysfunctionresultingfromcoronaryarterydisease,antiplateletandanticoagulanttherapyareeachassociatedwithareductionintheriskofSCD.,DatafromSOLVDpreventionandtreatmenttrials,RolesofStatinsinSCDPrevention,StatinsintheMADIT-IIStudy,.,VyasAK,HongshengGuo,MossAJ,etal.JAmCollCardiol2006;47:769-773,Statins,Placeboornotreatment,SCDMortality19%riskreductionp=0.003,LevantesiGetal.Meta-analysisofeffectofstatintreatmentonriskofsuddendeath.AmJCardiol.2007;100:1644-1650.,RolesofStatinsinSCDPrevention,Meta-analysisofeffectofstatintreatmentonriskofSCD,Rolesofn-3FattyAcidinSCDPrevention,.,Patie