急性心衰治療若干進展

急性心力衰竭藥物治療的

若干進展

2011.4內(nèi)容ASCEND-HFDOSE急性失代償性心衰的預后

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急性心衰診斷和治療指南ADHF的藥物治療終于取得了一些進展在過去30年中，急性失代償性心衰（ADHF）的藥物治療幾乎沒有進展ADHF治療新藥乏善可陳在不同醫(yī)院和不同醫(yī)生之間利尿劑的應(yīng)用劑量和應(yīng)用方式均大相徑庭，缺乏安全性和有效性的高質(zhì)量研究終于有些進展ASCEND-HF（AHA2010)DOSE最新結(jié)果（NEnglJMed3月3號在線）奈西立肽(Nesiritide，人類BNP)–一種激素樣物質(zhì)，除擴張動脈和靜脈外，還可促進利鈉利尿降低患者左室充盈壓和呼吸困難程度，緩解癥狀FDAapproved2001TheEffectsofNesiritideon

NeurohormonesInpatientswithevidenceofseverelysymptomaticfluidoverloadintheabsenceofsystemichypotension,vasodilatorssuchasintravenousnitroglycerin,nitroprussideorneseritidecanbebeneficialwhenaddedtodiureticsand/orinthosewhodonotrespondtodiureticsalone.TheHospitalizedPatient

SevereSymptomaticFluidOverloadNewIIIaIIbIIIAReportoftheACCF/AHATaskForceonPracticeGuidelinesBNP可用于治療急性心衰，患者的體征為肺充血/水腫，BP>90mmHg靜注BNP時，其輸注速率從0.015到0.03ug/kg/min均可，無論開始是否進行負荷推注（2ug/kg）。不推薦和其他靜注血管擴張劑聯(lián)用ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure20085個研究的薈萃分析：奈西立肽對腎功能影響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腎功能惡化的定義：SCr>0.5mg/dL.Circulation.2005;111:1487-1491MortalityWithin30DaysofTreatmentAssociatedWithNesiritideorControlTherapyWithOverallRiskRatioCalculatedbyMantel-HaenszelTestUsingaFixed-EffectsModel.Sackner-Bernstein,J.D.etal.JAMA2005;293:1900-1905Copyrightrestrictionsmayapply.薈萃3個小規(guī)模試驗：NSGETVMACPROACTIONASCEND-HF

奈西立肽治療失代償性心衰患者

臨床療效的短期研究

DukeHeartFailureResearchPager:970-0736NHLBIHeartFailure

ClinicalResearchNetworkBaylorDukeHarvardMayoClinicMinnesotaMontrealMorehouseUtahVermontPurpose在常規(guī)治療基礎(chǔ)上，通過雙盲安慰劑對照研究評價奈西立肽對于急性代償性心衰患者的療效和安全性.Doubleblindedstudymeaningsubjects,MD,andresearchteamareunawareofwhattreatmentisbeingreceived.入選標準靜息時呼吸困難肺淤血入院24小時內(nèi)存在心衰的癥狀和體征InterventionsRandomizedto1of2GroupsN=7141Nesiritideplusstandardofcare首先給予其靜脈注射負荷劑量的奈西立肽，然后持續(xù)靜脈滴注24h，共給藥7天PlaceboplusstandardofcareUSEOFOPENLABELNESIRITIDEISNOTALLOWEDATANYTIME!!Whyisthisstudybeingdone?DoesNesiritidedecreasere-hospitalizationordeathin30days?DoesNesiritidedecreasesymptomsofdyspneaat6and24hrsafterdruginitiated?復合主要終點NursingRoles在治療6小時和24小時填寫問卷表*和VAS量表問卷表和VAS量表內(nèi)容包括:自我評價呼吸困難程度健康狀態(tài)/一般情況,自我護理能力,疼痛,抑郁,體力7級評定*Foundinpatient’schartbox.30天復合終點30天復合終點的亞組分析腎臟安全性對ASCEND-HF評價ASCEND-HF研究澄清了既往質(zhì)疑，證實奈西立肽安全ASCEND-HF研究在給藥方案上可能存在問題：由于奈西利肽的有效半衰期比硝酸甘油和硝普鈉長，因此其副作用的持續(xù)時間可能較長,低血壓的發(fā)生率相對高采用保守（即無負荷量）和推薦劑量治療可減少并發(fā)癥內(nèi)容ASCEND-HFDOSEDiureticsandHeartFailureDiureticsaremainstayoftherapyforacuteheartfailure(givento>90%ofptsinADHERE)RelievesymptomsofdyspneaandedemainmostpatientsAssociatedwithvarietyofproblems:ElectrolyteabnormalitiesActivationofRAASandSNSDiureticresistanceIncreasedmortality?DiureticsandPCWPCirculation.1986;74:1303–1306.速尿靜推40-100mg

強心Ifpatientsarealreadyreceivingloopdiuretictherapy,theinitialintravenousdoseshouldequalorexceedtheirchronicoraldailydose.(LevelofEvidence:C).

TheHospitalizedPatient

TreatmentWithIntravenousLoopDiureticsNewAReportoftheACCF/AHATaskForceonPracticeGuidelinesTheHospitalizedPatient

IntensifyingtheDiureticRegimenNewWhendiuresisisinadequatetorelievecongestion,asevidencebyclinicalevaluation,thediureticregimenshouldbeintensifiedusingeither:

a.higherdosesofloopdiuretics;

b.additionofaseconddiuretic(suchas metolazone,spironolactoneorintravenous chlorthiazide)or

c.

Continuousinfusionofaloopdiuretic.AReportoftheACCF/AHATaskForceonPracticeGuidelines急性心衰患者利尿劑使用的指征及劑量液體潴留利尿劑日劑量（mg）

注釋中度速尿布美它尼托拉塞米20-40

0.5-110-20根據(jù)臨床癥狀口服或靜注，根據(jù)臨床反應(yīng)調(diào)整滴定速度，監(jiān)測血鉀、血鈉、血肌酐及血壓。嚴重速尿速尿滴注布美它尼托拉塞米40-1005-40mg/h

1-420-100靜注增加劑量優(yōu)于高沖擊劑量口服或靜注口服絆利尿劑抵抗加雙氫克尿噻或美托拉宗或螺內(nèi)酯50-100

2.5-1025-50聯(lián)合用藥優(yōu)于高劑量髓絆利尿劑，肌酐清除率>30ml/min時雙氫克尿噻效果更佳；無腎衰或血鉀正?；蚱蜁r螺內(nèi)酯是最佳選擇。堿中毒乙酰唑氨

0.5mg靜注袢利尿劑及噻嗪類利尿劑抵抗

增加多巴胺或多巴酚丁胺合并腎衰或低血鈉考慮使用超濾或血透DiureticOptimizationStrategiesEvaluationinAcuteHeartFailure

(DOSE)G.MichaelFelker,MD,MHS,FACCChristopherM.O’Connor,MD,FACConbehalfoftheNHLBIHeartFailureClinicalResearchNetwork利尿劑優(yōu)化策略治療急性心衰評價

ACC2010NEnglJMed2011;364:797-805AimsToevaluatethesafetyandefficacyofvariousinitialstrategiesoffurosemidetherapyinpatientswithADHFRouteofadministration:Q12hoursbolusContinuousinfusion

DosingLowintensification(過去日劑量)Highintensification(過去日劑量的2.5倍)ACC2010NEnglJMed2011;364:797-805允許48hr后根據(jù)患者臨床反應(yīng)調(diào)整治療方案AcuteHeartFailure(1symptomAND1sign)<24hoursafteradmission308例

2x2factorialrandomizationLowDose(1xoral)Q12IVbolus48hours