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:6daysHospitalreadmissionsHospitalreadmissions––20%at30days20%at30days––50%at6months50%at6monthsMortalityMortality––11.6%at30days11.6%at30days––33.1%at12months––50%at5years50%at5yearsRevCardiovascMed.2002;3(suppl4)ArchInternMed.2002;162InternMed.2002;162Acuteheartfailurewithsystolicdysfunction

Furosemide+/-VasodilatorSBP>100mmHgSBP85-100mmHgSBP<85mmHgVasodilator(NTG,SPN,BNP)Vasodilatorand/orinotropic(dobutamine,PDEIorlevosimendan)inotropicand/orDopamine>5ug/kg/minNoresponse:ReconsidermechanistictherapyinotropicagentsGoodresponse: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FDAapproved2001TheEffectsofNesiritideon

NeurohormonesInpatientswithevidenceofseverelysymptomaticfluidoverloadintheabsenceofsystemichypotension,vasodilatorssuchasintravenousnitroglycerin,nitroprussideorneseritidecanbebeneficialwhenaddedtodiureticsand/orinthosewhodonotrespondtodiureticsalone.TheHospitalizedPatient

SevereSymptomaticFluidOverloadNewIIIaIIbIIIAReportoftheACCF/AHATaskForceonPracticeGuidelinesBNP可用于治疗急性心衰，患者的体征为肺充血/水肿，BP>90mmHg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ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure20085个研究的荟萃分析：奈西立肽对肾功能影响Control,n/N(%)Nesiritide,n/N(%)

3114/29(14)15/74(20)3252/42(5)15/85(18)3269/102(9)36/203(18)VMAC45/216(21)74/273(27)Precedent9/83(11)29/162(18)Totals69/472(15)169/797(21)study肾功能恶化的定义：SCr>0.5mg/dL.Circulation.2005;111:1487-1491MortalityWithin30DaysofTreatmentAssociatedWithNesiritideorControlTherapyWithOverallRiskRatioCalculatedbyMantel-HaenszelTestUsingaFixed-EffectsModel.Sackner-Bernstein,J.D.etal.JAMA2005;293:1900-1905Copyrightrestrictionsmayapply.荟萃3个小规模试验：NSGETVMACPROACTIONASCEND-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:970-0736NHLBIHeartFailure

ClinicalResearchNetworkBaylorDukeHarvardMayoClinicMinnesotaMontrealMorehouseUtahVermontPurpose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InterventionsRandomizedto1of2GroupsN=7141Nesiritideplusstandardofcare首先给予其静脉注射负荷剂量的奈西立肽，然后持续静脉滴注24h，共给药7天PlaceboplusstandardofcareUSEOFOPENLABELNESIRITIDEISNOTALLOWEDATANYTIME!!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*Foundinpatient’schartbox.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-HFDOSEDiureticsandHeartFailureDiureticsaremainstayoftherapyforacuteheartfailure(givento>90%ofptsinADHERE)RelievesymptomsofdyspneaandedemainmostpatientsAssociatedwithvarietyofproblems:ElectrolyteabnormalitiesActivationofRAASandSNSDiureticresistanceIncreasedmortality?DiureticsandPCWPCirculation.1986;74:1303–1306.速尿静推40-100mg

强心Ifpatientsarealreadyreceivingloopdiuretictherapy,theinitialintravenousdoseshouldequalorexceedtheirchronicoraldailydose.(LevelofEvidence:C).

TheHospitalizedPatient

TreatmentWithIntravenousLoopDiureticsNewAReportoftheACCF/AHATaskForceonPracticeGuidelinesTheHospitalizedPatient

IntensifyingtheDiureticRegimenNewWhendiuresisisinadequatetorelievecongestion,asevidencebyclinicalevaluation,thediureticregimenshouldbeintensifiedusingeither:

a.higherdosesofloopdiuretics;

b.additionofaseconddiuretic(suchas metolazone,spironolactoneorintravenous chlorthiazide)or

c.

Continuousinfusionofaloopdiuretic.AReportoftheACCF/AHATaskForceonPracticeGuidelines急性心衰患者利尿剂使用的指征及剂量液体潴留利尿剂日剂量（mg）

注释中度速尿布美它尼托拉塞米20-40

0.5-110-20根据临床症状口服或静注，根据临床反应调整滴定速度，监测血钾、血钠、血肌酐及血压。严重速尿速尿滴注布美它尼托拉塞米40-1005-40mg/h

1-420-100静注增加剂量优于高冲击剂量口服或静注口服绊利尿剂抵抗加双氢克尿噻或美托拉宗或螺内酯50-100

2.5-1025-50联合用药优于高剂量髓绊利尿剂，肌酐清除率>30ml/min时双氢克尿噻效果更佳；无肾衰或血钾正常或偏低时螺内酯是最佳选择。碱中毒乙酰唑氨

0.5mg静注袢利尿剂及噻嗪类利尿剂抵抗

增加多巴胺或多巴酚丁胺合并肾衰或低血钠考虑使用超滤或血透DiureticOptimizationStrategiesEvaluationinAcuteHeartFailure

(DOSE)G.MichaelFelker,MD,MHS,FACCChristopherM.O’Connor,MD,FACConbehalfoftheNHLBIHeartFailureClinicalResearchNetwork利尿剂优化策略治疗急性心衰评价

ACC2010NEnglJMed2011;364:797-805AimsToevaluatethesafetyandefficacyofvariousinitialstrategiesoffurosemidetherapyinpatientswithADHFRouteofadministration:Q12hoursbolusContinuousinfusion

DosingLowintensification(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

2x2factorialrandomizationLowDose(1xoral)Q12IVbolus48hours