ARB治療房顫(GISSI AF)課件

StudyResultsBackground:experimentaldataRemodeling,whichappearsearlyaftertheonsetofAF,playsanimportantroleintheinitiationandmaintenanceofAF:electrical:shorteningofatrialeffectiverefractoryperiod(AERP)associatedwithlossofratedependencyoftheAERPledtoanincreasedatrialvulnerabilitystructural:rapidatrialratesareassociatedwithenlargementofbothatrialcavities,leadingtostructuralremodelingInanimalmodels,blockersoftheRAAShavebeenshowntobeabletomodulatebothtypesofremodelingCardiovascRes2002;54:456–461JAmCollCardiol2003;41:2197–2204Circulation2001;104:2608–2614HealeyJSetal.JACC2005;45:1832-39ToevaluatewhetherinpatientswithpreviousAFepisodestreatedwiththebestrecommendedtherapiestheadditionofvalsartancanpreventAFrecurrenceVisit12WeekDays-5to-1Day0Randomization324458624752StudyDrugTreatmentplaceboplaceboplacebo80mgvalsartan160mgvalsartan320mgvalsartanStudyDesignAllpatientshavebeenprovidedwithatranstelephonicmonitoringtoolAtleastoneofthefollowingunderlyingcardiovasculardiseases/comorbidities:heartfailure/documentedhistoryofLVdysfunction(definedasanEF<40%)historyofhypertension6monthswith/withoutLVHtypeIIdiabetesmellitusdocumentedhistoryofstrokeorperipheralvasculardiseasedocumentedhistoryofcoronaryarterydiseaseloneatrialfibrillationwithdocumentedLAdilation(LAdiameter45mmformenand40mmforwomen)InclusioncriteriaCo-primary

End-points

TimetofirstrecurrenceofAFRateofpatientswithmorethanone AF episode

Secondary

End-points

TotalnumberofAFepisodesNumberofhospitalizationsforCVreasonsNumberofall-causehospitalizationsIncidenceofthromboemboliceventsSafetyprofileStudy

End-pointsValsartan(n.722)Placebo(n.720)Pvalue*Heartfailureand/orEF<40%7.8%8.1%0.83Historyofhypertension≥6months85.7%85.0%0.69DiabetesMellitus13.2%16.1%0.11Historyofstroke4.4%3.8%0.51Peripheralarterydisease(PAD)5.1%3.1%0.047DocumentedCAD15.4%9.4%0.0006Loneatrialfibrillation(withleftatrialdilation)10.8%13.1%0.19Inclusionclinicalcriteria*Chi-squaretestValsartan(n.722)Placebo(n.720)PvalueAge(mean±SD),years>70years67.5±9.543.8%68.2±8.945.1%0.14°0.60*Females37.0%38.5%0.56*BMI(mean±SD),kg/m228.0±4.527.7±4.20.19°Heartrate(mean±SD),bpm63.9±10.464.3±10.80.40°Systolicbloodpressure(mean±SD),mmHg138.2±16.7139.0±16.90.40°Diastolicbloodpressure(mean±SD),mmHg81.5±8.581.6±9.00.92°Baselinecharacteristics°T-test*Chi-squaretestDosageofstudytreatments2weeks4weeks8weeks24weeksSystolicpressuremodificationsbystudytreatmentsTimetofirstrecurrenceofAF(n.1442)Valsartan:371/722(51.4%)Placebo:375/720(52.1%)Adjusted*HR0.9996%CI0.85-1.15Pvalue0.84PtsatriskValsartanPlacebo*AdjustedforACE-I,amiodaroneuse,cardioversion,PAD,CAD722586524491465445423398383368356343260720589520484454435407387377359344334254DaysRateofptswith>1episodeofAFValsartan:194/722(26.9%)Placebo:201/720(27.9%)OR0.9599%CI*0.70-1.29Pvalue0.66*The99%CIwascalculatedbyLogisticRegressionmodelTimetofirstrecurrenceofAF:prespecifiedsubgroupanalysisValsartanEvents/Patients(%)PlaceboEvents/Patients(%)HR95%CI*Age<69yearsAge≥69years183/368(49.7)188/354(53.1)186/353(52.7)189/367(51.5)0.941.040.76-1.150.85-1.27HFand/orLVDNoHFand/orLVD27/56(48.2)344/666(51.7)32/58(55.2)343/662(51.8)0.811.000.48-1.350.86-1.16ACE-INoACE-I217/420(51.7)154/302(51.0)208/402(51.7)167/318(52.5)1.000.960.83-1.210.77-1.19AmiodaroneNoAmiodaroneOtherantiarrhytmics109/253(43.1)262/469(55.9)154/277(55.6)113/248(45.6)262/472(55.5)150/268(56.0)0.931.010.990.72-1.210.85-1.200.79-1.24BetablockersNoBetablockers110/223(49.3)261/499(52.3)110/213(51.6)265/507(52.3)0.961.000.74-1.250.84-1.18LoneAF42/78(53.9)55/94(58.5)0.970.65-1.45*The95%CIwascalculatedbyCoxproportionalhazardsmodel00.511.52SummaryThe1-yearrateofrecurrenceofAFintheGISSI-AFpopulationwasnearly52%irrespectiveoftheunderlyingCVdisorderandthebaselinecharacteristicsofpatientsTheneutraleffectofvalsartan(upto320mg/daily)wassimilarinallpredefinedsubgroupsofpatients,withtheexceptionofthosewithHF/LVDforwhomabeneficialeffect(notsignificant)wasobservedRobustnessofGISSI-AFresultsThelargestprospectiveRCTeverconductedtestingRAASblockersinpatientswithAFAdequatelypowered(correctassumptionsintermsof1-yearrateofrecurrenceofAF):50%predictedvs52%observed599predictedeventsvs746observedeventsDifferentlyfrompost-hocorsecondaryanalysesofothertrials,theoccurrenceofAFwasspecificallyevaluatedthroughperiodicalECGandtranstelephonicmonitoringTheadherencetostudytreatmentsandprocedureswasmaximized:Maximaldosage(320mg)usedandwelltoleratedbymorethan80%ofthepatientsRateofpermanentdiscontinuationslessthan15%over1yearMorethan80%oftheexpectedtranstelephonicECGhavebeenactuallytransmittedNopatientslosttofollow-upAlleventscentrallyvalidatedbyanad-hoccommitteeRobustnessofGISSI-AFresultsInterpretation(1)ModulationoftheRAASappearsinadequatefor“secondary”preventionofAF:GISSIAFpatientshadagreaterrateofAFrecurrence(10%vsmorethan50%)InpatientswithadocumentedhistoryofAF

theelectricalremodelingwas