急性心衰治疗若干进展

.,急性心力衰竭药物治疗的若干进展,2011.4,.,内容,ASCEND-HFDOSE,.,急性失代偿性心衰的预后,Medianlengthofhospitalstay:6daysHospitalreadmissionsHospitalreadmissions20%at30days20%at30days50%at6months50%at6monthsMortalityMortality11.6%at30days11.6%at30days33.1%at12months50%at5years50%at5years,RevCardiovascMed.2002;3(suppl4)ArchInternMed.2002;162InternMed.2002;162,.,Acuteheartfailurewithsystolicdysfunction,Furosemide+/-Vasodilator,SBP100mmHg,SBP85-100mmHg,SBP5ug/kg/min,Noresponse:Reconsidermechanistictherapyinotropicagents,Goodresponse:OraltherapyACEI,ESC2005急性心衰诊断和治疗指南,.,ADHF的药物治疗终于取得了一些进展,在过去30年中，急性失代偿性心衰（ADHF）的药物治疗几乎没有进展ADHF治疗新药乏善可陈在不同医院和不同医生之间利尿剂的应用剂量和应用方式均大相径庭，缺乏安全性和有效性的高质量研究终于有些进展ASCEND-HF（AHA2010)DOSE最新结果（NEnglJMed3月3号在线）,.,奈西立肽(Nesiritide，人类BNP)一种激素样物质，除扩张动脉和静脉外，还可促进利钠利尿降低患者左室充盈压和呼吸困难程度，缓解症状FDAapproved2001,.,TheEffectsofNesiritideonNeurohormones,.,Inpatientswithevidenceofseverelysymptomaticfluidoverloadintheabsenceofsystemichypotension,vasodilatorssuchasintravenousnitroglycerin,nitroprussideorneseritidecanbebeneficialwhenaddedtodiureticsand/orinthosewhodonotrespondtodiureticsalone.,TheHospitalizedPatient,SevereSymptomaticFluidOverload,New,AReportoftheACCF/AHATaskForceonPracticeGuidelines,.,BNP可用于治疗急性心衰，患者的体征为肺充血/水肿，BP90mmHg静注BNP时，其输注速率从0.015到0.03ug/kg/min均可，无论开始是否进行负荷推注（2ug/kg）。不推荐和其他静注血管扩张剂联用,ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure2008,.,5个研究的荟萃分析：奈西立肽对肾功能影响,Control,n/N(%),Nesiritide,n/N(%),study,肾功能恶化的定义：SCr0.5mg/dL.,Circulation.2005;111:1487-1491,.,MortalityWithin30DaysofTreatmentAssociatedWithNesiritideorControlTherapyWithOverallRiskRatioCalculatedbyMantel-HaenszelTestUsingaFixed-EffectsModel.,Sackner-Bernstein,J.D.etal.JAMA2005;293:1900-1905,Copyrightrestrictionsmayapply.,荟萃3个小规模试验：NSGETVMACPROACTION,.,ASCEND-HF奈西立肽治疗失代偿性心衰患者临床疗效的短期研究,DukeHeartFailureResearchPager:970-0736,.,NHLBIHeartFailureClinicalResearchNetwork,BaylorDukeHarvardMayoClinicMinnesotaMontrealMorehouseUtahVermont,.,Purpose,在常规治疗基础上，通过双盲安慰剂对照研究评价奈西立肽对于急性代偿性心衰患者的疗效和安全性.Doubleblindedstudymeaningsubjects,MD,andresearchteamareunawareofwhattreatmentisbeingreceived.,.,.,入选标准,静息时呼吸困难肺淤血,入院24小时内存在心衰的症状和体征,.,Interventions,USEOFOPENLABELNESIRITIDEISNOTALLOWEDATANYTIME!,.,Whyisthisstudybeingdone?DoesNesiritidedecreasere-hospitalizationordeathin30days?DoesNesiritidedecreasesymptomsofdyspneaat6and24hrsafterdruginitiated?,复合主要终点,.,NursingRoles,在治疗6小时和24小时填写问卷表*和VAS量表问卷表和VAS量表内容包括:自我评价呼吸困难程度健康状态/一般情况,自我护理能力,疼痛,抑郁,体力7级评定*Foundinpatientschartbox.,.,.,.,30天复合终点,.,30天复合终点的亚组分析,.,肾脏安全性,.,对ASCEND-HF评价,ASCEND-HF研究澄清了既往质疑，证实奈西立肽安全ASCEND-HF研究在给药方案上可能存在问题：由于奈西利肽的有效半衰期比硝酸甘油和硝普钠长，因此其副作用的持续时间可能较长,低血压的发生率相对高采用保守（即无负荷量）和推荐剂量治疗可减少并发症,.,内容,ASCEND-HFDOSE,.,DiureticsandHeartFailure,Diureticsaremainstayoftherapyforacuteheartfailure(givento90%ofptsinADHERE)RelievesymptomsofdyspneaandedemainmostpatientsAssociatedwithvarietyofproblems:ElectrolyteabnormalitiesActivationofRAASandSNSDiureticresistanceIncreasedmortality?,.,DiureticsandPCWP,Circulation.1986;74:13031306.,.,.,速尿静推40-100mg,强心,.,Ifpatientsarealreadyreceivingloopdiuretictherapy,theinitialintravenousdoseshouldequalorexceedtheirchronicoraldailydose.(LevelofEvidence:C).,TheHospitalizedPatient,TreatmentWithIntravenousLoopDiuretics,New,AReportoftheACCF/AHATaskForceonPracticeGuidelines,.,TheHospitalizedPatient,IntensifyingtheDiureticRegimen,New,Whendiuresisisinadequatetorelievecongestion,asevidencebyclinicalevaluation,thediureticregimenshouldbeintensifiedusingeither:a.higherdosesofloopdiuretics;b.additionofaseconddiuretic(suchasmetolazone,spironolactoneorintravenouschlorthiazide)orc.Continuousinfusionofaloopdiuretic.,AReportoftheACCF/AHATaskForceonPracticeGuidelines,.,急性心衰患者利尿剂使用的指征及剂量,.,DiureticOptimizationStrategiesEvaluationinAcuteHeartFailure(DOSE),G.MichaelFelker,MD,MHS,FACCChristopherM.OConnor,MD,FACConbehalfoftheNHLBIHeartFailureClinicalResearchNetwork,利尿剂优化策略治疗急性心衰评价,ACC2010NEnglJMed2011;364:797-805,.,Aims,ToevaluatethesafetyandefficacyofvariousinitialstrategiesoffurosemidetherapyinpatientswithADHFRouteofadministration:Q12hoursbolusContinuousinfusionDosingLowintensification(过去日剂量)Highintensification(过去日剂量的2.5倍),ACC2010NEnglJMed2011;364:797-805,允许48hr后根据患者临床反应调整治疗方案,.,AcuteHeartFailure(1symptomAND1sign)24hoursafteradmission308例,2x2factorialrandomization,LowDose(1xoral)Q12IVbolus,48hours,1)Changetooraldiuretics2)continuecurrentstrategy3)50%increaseindose,Co-primaryendpoints,HighDose(2.5xoral)Q12IVbolus,LowDose(1xoral)Continuousinfusion,HighDose(2.5xoral)Continuousinfusion,72hours,StudyDesign,Clinicalendpoints,60days,.,主要终点,主要疗效终点：基线至72h内患者对症状的总体自评次要疗效终点呼吸困难、体重变化、体液净损失、受充血影响的患者比例、肾功能恶化、心力衰竭恶化,.,PatientGlobalAssessmentVASAUC:Q12vs.Continuous,PtGlobalAssessmentbyVAS,Q12VASAUC,mean(SD)=4236(1440)ContinuousVASAUC,mean(SD)=4373(1404)P=0.47,Q12,Continuous,Hours,ACC2010NEnglJMed2011;364:797-805,.,PatientGlobalAssessmentVASAUC:Lowvs.HighIntensification,Hours,PtGlobalAssessmentbyVAS,Low,High,LowVASAUC,mean(SD)=4171(1436)HighVASAUC,mean(SD)=4430(1401)P=0.06,ACC2010NEnglJMed2011;364:797-805,.,SecondaryEndpoints:Lowvs.HighIntensification,ACC2010NEnglJMed2011;364:797-805,.,死亡、心衰再住院或再进急诊室的复合终点两种给药方式、两种剂量的比较,NEnglJMed2011;364:797-805,.,ChangeinCreatinineat72hours,Q12Continuous,p=0.45,p=0.21,0.05,0.07,0.04,0.08,0,0.05,0.1,0.15,ChangeinCreatinine(mg/dL),LowHigh,ACC2010NE