Aldosteronereceptorantagonists(mineralocorticoidreceptorantagonises)RALES、EPHESUS、EMPHASIS-HF試驗(yàn)奠定了醛固酮受體拮抗劑在慢性收縮性心力衰竭的地位。醛固酮受體拮抗劑應(yīng)用的注意事項。作用機(jī)理醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。衰竭心臟心室醛固酮生成及活化增加，且與心衰嚴(yán)重程度成正比。長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。因此，加用醛固酮受體拮抗劑，可抑制醛固酮的有害作用，對心衰患者有益。入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。

排除標(biāo)準(zhǔn)：原發(fā)病為瓣膜病，UA,等，Cr>221μmol/L,K>5mmol/L。RALES基線臨床特征臨床特征安慰劑組（841例）螺內(nèi)酯組（822例）NYHA心功能分級Ⅱ級3（0.4%）4（0.5%）

Ⅲ581（69%）592（72%）

Ⅳ257（31%）226（27%）LVEF(%)25.2±6.825.6±6.7藥物：袢利尿劑100%100%ACEI94%95%平均ACEI劑量（mg/d)

卡托普利62.163.4

依那普利16.513.5

福辛普利13.115.5全因死亡率平均隨訪24月亞組分析106μmol/l入選標(biāo)準(zhǔn)：AMI后3~14d,LVEF≤40%，伴心衰相關(guān)的肺

部濕啰音、胸片提示肺水腫、S3；或合并糖尿病。

排除標(biāo)準(zhǔn)：Cr>221μmol/L，K>5mmol/L，應(yīng)用其它潴

鉀利尿劑等。EPHESUS97theRateofDeathfromAnyCause平均隨訪16月theRateofDeathfrom

Cardiovascular

CausesorHospitalizationforCardiovascularEventstheRateofSuddenDeathfromCardiacCauses長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。Atbaseline,Crlevelswere117.JCardFail,2004,10(4):297-303.醛固酮受體拮抗劑適應(yīng)癥CarefulmonitoringofK,renalfunction,anddiureticdosingshouldbeperformedatinitiationandcloselyfollowedthereaftertominimizeriskofhyperkalemiaandrenalinsufficiency.K<4mmol/L

K≥4mmol/L

P=0.適用于LVEF≤35%、NYHAⅡ~Ⅳ級的患者；Theserumpotassiumconcentrationwasmeasured48hoursaftertheinitiationoftreatment,atone,four,andfiveweeks,atallscheduledstudyvisits,andwithinoneweekafteranychangeofdose.入院后查NT-proBNP4279pg/ml，Cr526μmol/L，K7.醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。改變了慢性收縮性心衰治療中ACEI、β受體阻滯劑之后加用藥物的選擇。12/5胸部CT：慢支、肺氣腫，兩肺支擴(kuò)并感染，心臟增大，主動脈和冠狀動脈硬化。Therateofhospitalizationforheartfailuredeclinedgraduallyduringthestudyperiod,withnostatisticallysignificantchangeinthisvariableafterthepublicationofRALESAMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。為避免高鉀血癥和腎功能損害，血鉀>5mmol/L,腎功能受損（Cr>221μmol/L，或eGFR<30ml?min-1?1.Aldosteronereceptorantagonists(mineralocorticoidreceptorantagonises)醛固酮受體拮抗劑能改善慢性收縮性心力衰竭（左心衰竭）患者的預(yù)后。TheriskofhyperkalemiaincreasesprogressivelywhenCris>141.利尿劑+ACEI(或ARB）+β受體阻滯劑Closemonitoringofserumpotassiumisrequired;Klevelsandrenalfunctionaremosttypicallycheckedin3dandat1wkafterinitiatingtherapyandatleastmonthlyforthefirst3mo,andevery3monthsthereafter.K<4mmol/L

K≥4mmol/L

P=0.29

Cr<97μmol/L

Cr≥97μmol/L

P=0.03亞組分析入選標(biāo)準(zhǔn)：≥55歲，NYHA心功能分級Ⅱ級，LVEF≤30%（若30~35%，QRS波>130ms），已接受ACEI或（和）ARB、β受體阻滯劑，6個月內(nèi)因心血管疾病住院（若無住院，BNP≥250pg/ml,或NT-proBNP≥500pg/ml(男），750pg/ml（女））。排除標(biāo)準(zhǔn)：AMI，NYHA心功能分級Ⅲ級、Ⅳ級，K>5mmol/L，eGFR<30ml/min/1.73m2。EMPHASIS-HF100.8平均隨訪21月eGFR<60ml/min/1.73m2≥60ml/min/1.73m2醛固酮受體拮抗劑適應(yīng)癥LVEF≤35%、NYHAⅡ~Ⅳ級的患者；已使用ACEI（或ARB）和β受體阻滯劑治療，仍持續(xù)有癥狀的患者（Ⅰ類，A級）AMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。

中國心力衰竭診斷和治療指南2014

慢性收縮性心衰的基本治療方案從“黃金搭檔”（ACEI加β受體阻滯劑）轉(zhuǎn)變?yōu)椤敖鹑恰保ㄇ皟烧呒尤┕掏荏w拮抗劑）醛固酮受體拮抗劑是繼ACEI、β受體阻滯劑之后又一個可以應(yīng)用于所有伴癥狀的慢性收縮性心衰患者，并可改善患者的預(yù)后。改變了慢性收縮性心衰治療中ACEI、β受體阻滯劑之后加用藥物的選擇。過去存在多種選擇，包括ARB、地高辛等?，F(xiàn)在，醛固酮受體拮抗劑是唯一的選擇。是繼β受體阻滯劑后又一種證實(shí)可顯著降低慢性收縮性心衰患者心臟性猝死且能長期使用的藥物。醛固酮受體拮抗劑應(yīng)用注意事項Closemonitoringofserumpotassiumisrequired;Klevelsandrenalfunctionaremosttypicallycheckedin3dandat1wkafterinitiatingtherapyandatleastmonthlyforthefirst3mo,andevery3monthsthereafter.AMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。Atbaseline,Crlevelswere117.為避免高鉀血癥和腎功能損害，血鉀>5mmol/L,腎功能受損（Cr>221μmol/L，或eGFR<30ml?min-1?1.查體：HR90bpm，R20bpm，BP140/90mmHg。73m

2),and/orK>5.長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。Aldosteronereceptorantagonists(mineralocorticoidreceptorantagonises)是繼β受體阻滯劑后又一種證實(shí)可顯著降低慢性收縮性心衰患者心臟性猝死且能長期使用的藥物。JCardFail,2004,10(4):297-303.醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。有“高血壓”病史10余年，服藥治療，血壓控制不詳。(CLASSⅢLevelofEvidence:B)Aldosteronereceptorantagonists(mineralocorticoidreceptorantagonises)適用于LVEF≤35%、NYHAⅡ~Ⅳ級的患者；仍NYHAⅡ~Ⅳ級，LVEF≤35%6μmol/L±11.入選標(biāo)準(zhǔn)：AMI后3~14d,LVEF≤40%，伴心衰相關(guān)的肺

部濕啰音、胸片提示肺水腫、S3；3/5醫(yī)囑：螺內(nèi)酯40mgbid，速尿20mgqd。診斷：高血壓、心功能不全。AfterthepublicationofRALES,however,therateofprescriptionsforthisdrugincreasedbyafactorofaboutfive,to149per1000bylate2001TherateofhospitaladmissionforhyperkalemiaincreasedbyafactorofaboutthreeafterthepublicationofRALES,to11.0per1000bylate2001therateofhyperkalemia-associatedwithin-hospitaldeathincreasedbyafactorofaboutthreeafterthepublicationofRALES,to2.0per1000bylate2001

Therateofhospitalizationforheartfailuredeclinedgraduallyduringthestudyperiod,withnostatisticallysignificantchangeinthisvariableafterthepublicationofRALESSvenssonM,etal.JCardFail,2004,10(4):297-303.125patientswithwereLVEF≤45%.Bloodtestswereperformedbimonthlyormorefrequentlyifnecessary.Atbaseline,Crlevelswere117.6±6.5μmol/l,serumKwas4.2±0.3mmol/L.Themeanfollow-upperiodwas11months.MeanpeakCrwas167.6μmol/L±11.9(45%increasefrombaseline),meanpeakserumKwas5.0±0.4mmol/L(21%increasefrombaseline).

36%ofthepatientsdevelopedhyperkalemia(>5mmol/L),with10%havingserumK>6mmol/L.

Anincreaseinserumcreatinineof>20%wasseenin55%,andin24%anincreaseof>50%wasfound.RAILESMETHODSPatients

criteriaforexclusionwereaserumCr

>221μmol/LorK>5.0mmol/L.

Follow-up

measurementsofserumK,wereconductedevery4weeksforthefirst12weeks,thenevery3monthsforupto1yearandevery6monthsthereafteruntiltheendofthestudy…….Studymedicationcouldbewithheldintheeventofserioushyperkalemia,aserumCr≥354μmol/L.

AlthoughtheentrycriteriaforRAILESexcludedpatientswithaCr>221μmol/L,themajorityofpatientshadmuchlowercreatinine(95%ofpatientshadCr≤150.3μmol/L）EPHESUS

Exclusion:serumCr

>221μmol/LorK>5.0mmol/L.

Follow-upvisitsoccurredatoneandfourweeks,threemonths,andeverythreemonthsthereafteruntiltheterminationofthestudy.Theserumpotassiumconcentrationwasmeasured48hoursaftertheinitiationoftreatment,atone,four,andfiveweeks,atallscheduledstudyvisits,andwithinoneweekafteranychangeofdose.

Crshouldbe≤221

μmol/Linmenor≤176.8umol/Linwomen(oreGFR>30mL/min/1.73m2),andKshouldbe≤5.0mmol/L.CarefulmonitoringofK,renalfunction,anddiureticdosingshouldbeperformedatinitiationandcloselyfollowedthereaftertominimizeriskofhyperkalemiaandrenalinsufficiency.(CLASSI,LevelofEvidence:A)

AldosteronereceptorantagonistsarerecommendedtoInappropriateuseofaldosteronereceptorantagonistsispotentiallyharmfulbecauseoflife-threateninghyperkalemiaorrenalinsufficiencywhenserumcreatinineis>221μmol/Linmenor>176.8μmol/Linwomen(orGFR<30mL/min/1.73m

2),and/orK>5.0mmol/L.(CLASSⅢLevelofEvidence:B)若起始用藥后血K升高≤6mmol/L或出現(xiàn)腎功能惡化，則不加量直至血K<5mmol/l。確定高鉀血癥或腎功能不全去除后72h可考慮減量再使用。StrategiestoMinimizetheRiskofHyperkalemiainPatientsTreatedWithAldosteroneAntagonistsTheriskofhyperkalemiaincreasesprogressivelywhenCris>141.4μmol/L,orGFR>30mL/min/1.73m2.BaselineserumK>5.0mmol/L.Aninitialdoseofspironolactoneof12.5mgoreplerenone25mgistypical.TheriskofhyperkalemiaisincreasedwithconcomitantuseofhigherdosesofACEinhibitors(captopril75mgdaily;enalaprilorlisinopril10mgdaily).Inmostcircumstances,potassiumsupplementsarediscontinuedorreduced.Closemonitoringofserumpotassiumisrequired;Klevelsandrenalfunctionaremosttypicallycheckedin3dandat1wkafterinitiatingtherapyandatleastmonthly

forthefirst3mo,andevery3monthsthereafter.ConclusionsandRelevanceInthisrandomizedcontrolledtrial,long-termaldosteronereceptorblockadeimprovedleftventriculardiastolicfunction

butdidnotaffectmaximalexercisecapacity,patientsymptoms,orqualityoflifeinpatientswithheartfailurewithpreservedejectionfraction.WhethertheimprovedleftventricularfunctionobservedintheAldo-DHFtrialisofclinicalsignificancerequiresfurtherinvestigationinlargerpopulations.醛固酮受體拮抗劑在慢性心力衰竭（原發(fā)病為瓣膜病、LVEF保留的心力衰竭、慢性右心衰竭）、急性心力衰竭的應(yīng)用尚缺乏循證醫(yī)學(xué)證據(jù)。病例1住院號：02178279歲女性，因“反復(fù)咳嗽40年，氣促10年，加重7天”于2014-5-2入院。有“高血壓”病史10余年，服藥治療，血壓控制不詳。查體：P88bpm，R22bpm，BP86/55mmHg，雙肺少量濕啰音。雙下肢無浮腫。入院診斷AECOPD，

慢性肺源性心臟病失代償期？高血壓，慢性腎功能不全。入院后查NT-proBNP4279pg/ml，Cr526μmol/L，K7.18mmol/L（2/5）。3/5醫(yī)囑：螺內(nèi)酯40mgbid，速尿20mgqd。3/5復(fù)查Cr397μmol/L，K5.4mmol/L。4/5下午請我科會診后停用螺內(nèi)酯。12/5胸部CT：慢支、肺氣腫，兩肺支擴(kuò)并感染，心臟增大，主動脈和冠狀動脈硬化。12/5癥狀緩解出院。2013-1-28UCG：老年退行性瓣膜病，二尖瓣、主動脈瓣、三尖瓣輕度關(guān)閉不全，LVEF78%(正常值54~80%）。theRateofSuddenDeathfromCardiacCauses改變了慢性收縮性心衰治療中ACEI、β受體阻滯劑之后加用藥物的選擇。為避免高鉀血癥和腎功能損害，血鉀>5mmol/L,腎功能受損（Cr>221μmol/L，或eGFR<30ml?min-1?1.慢性收縮性心衰的基本治療方案從“黃金搭檔”（ACEI加β受體阻滯劑）轉(zhuǎn)變?yōu)椤敖鹑恰保ㄇ皟烧呒尤┕掏荏w拮抗劑）病例1住院號：021782仍NYHAⅡ~Ⅳ級，LVEF≤35%AMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。適用于LVEF≤35%、NYHAⅡ~Ⅳ級的患者；0per1000bylate2001處方：依那普利5mgqd，琥珀酸美托洛爾47.EMPHASIS-HFtheRateofSuddenDeathfromCardiacCauses≥60ml/min/1.Anincreaseinserumcreatinineof>20%wasseenin55%,andin24%anincreaseof>50%wasfound.8μmol/Linwomen(orGFR<30mL/min/1.64歲男性，因“心悸2天”于2014-4-21就診。Theserumpotassiumconcentrationwasmeasured48hoursaftertheinitiationoftreatment,atone,four,andfiveweeks,atallscheduledstudyvisits,andwithinoneweekafteranychangeofdose.79歲女性，因“反復(fù)咳嗽40年，氣促10年，加重7天”于2014-5-2入院。福辛普利有“冠心病、心房顫動”病史。病例2（門診患者）

64歲男性，因“心悸2天”于2014-4-21就診。有“冠心病、心房顫動”病史。查體：HR90bpm，R20bpm，BP140/90mmHg。診斷：冠心病、高血壓。處方：依那普利5mgqd，琥珀酸美托洛爾47.5mgqd，拜阿司匹林0.1qd，螺內(nèi)酯

20mgqd。25/4復(fù)診，出現(xiàn)活動后氣促，雙下肢浮腫。診斷：高血壓、心功能不全。加用速尿20mgqd。有充血癥狀/體征無充血癥狀/體征利尿劑+ACEI(或ARB）+β受體阻滯劑ACEI(或ARB）+β受體阻滯劑仍NYHAⅡ~Ⅳ級，LVEF≤35%加醛固酮受體拮抗劑仍NYHAⅡ~Ⅳ級，LVEF≤35%，竇性心律且心率≥70次/分仍為NYHAⅡ~Ⅳ級，LVEF≤45%加伊伐布雷定加地高辛↓↓↓↓↓↓↓↓↓慢性HF-REF(NYHAⅡ~Ⅳ級）藥物治療流程小結(jié)醛固酮受體拮抗劑能改善慢性收縮性心力衰竭（左心衰竭）患者的預(yù)后。適用于LVEF≤35%、NYHAⅡ~Ⅳ級的患者；已使用ACEI（或ARB）和β受體阻滯劑治療，仍持續(xù)有癥狀的患者（Ⅰ類，A級）；AMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。為避免高鉀血癥和腎功能損害，血鉀>5mmol/L,腎功能受損（Cr>221μmol/L，或eGFR<30ml?min-1?1.73m-2）不宜應(yīng)用。定期檢測血鉀和腎功能，如血鉀>5.5mmol/L,應(yīng)減量或停用；從小劑量起始，逐漸加量，尤其螺內(nèi)酯不推薦大劑量。謝謝作用機(jī)理醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。衰竭心臟心室醛固酮生成及活化增加，且與心衰嚴(yán)重程度成正比。長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。因此，加用醛固酮受體拮抗劑，可抑制醛固酮的有害作用，對心衰患者有益。入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。

排除標(biāo)準(zhǔn)：原發(fā)病為瓣膜病，UA,等，Cr>221μmol/L,K>5mmol/L。RALES亞組分析106μmol/l醛固酮受體拮抗劑應(yīng)用注意事項therateofhyperkalemia-associatedwithin-hospitaldeathincreasedbyafactorofaboutthreeafterthepublicationofRALES,to2.0per1000bylate2001

AMI后，LVEF≤40%，有心衰癥狀或既往有糖尿病史者。12/5胸部CT：慢支、肺氣腫，兩肺支擴(kuò)并感染，心臟增大，主動脈和冠狀動脈硬化。Therateofhospitalizationforheartfailuredeclinedgraduallyduringthestudyperiod,withnostatisticallysignificantchangeinthisvariableafterthepublicationofRALES已使用ACEI（或ARB）和β受體阻滯劑治療，仍持續(xù)有癥狀的患者（Ⅰ類，A級）；JCardFail,2004,10(4):297-303.醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。入院后查NT-proBNP4279pg/ml，Cr526μmol/L，K7.查體：HR90bpm，R20bpm，BP140/90mmHg。適用于LVEF≤35%、NYHAⅡ~Ⅳ級的患者；12/5胸部CT：慢支、肺氣腫，兩肺支擴(kuò)并感染，心臟增大，主動脈和冠狀動脈硬化。73m-2）不宜應(yīng)用。ACEI入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者?！?0ml/min/1.EMPHASIS-HF79歲女性，因“反復(fù)咳嗽40年，氣促10年，加重7天”于2014-5-2入院。長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。AfterthepublicationofRALES,however,therateofprescriptionsforthisdrugincreasedbyafactorofaboutfive,to149per1000bylate2001有“高血壓”病史10余年，服藥治療，血壓控制不詳。利尿劑+ACEI(或ARB）+β受體阻滯劑醛固酮受體拮抗劑能改善慢性收縮性心力衰竭（左心衰竭）患者的預(yù)后。EPHESUS

Exclusion:serumCr

>221μmol/LorK>5.0mmol/L.

Follow-upvisitsoccurredatoneandfourweeks,threemonths,andeverythreemonthsthereafteruntiltheterminationofthestudy.Theserumpotassiumconcentrationwasmeasured48hoursaftertheinitiationoftreatment,atone,four,andfiveweeks,atallscheduledstudyvisits,andwithinoneweekafteranychangeofdose.Theserumpotassiumconcentrationwasmeasured48hoursaftertheinitiationoftreatment,atone,four,andfiveweeks,atallscheduledstudyvisits,andwithinoneweekafteranychangeofdose.K<4mmol/L

K≥4mmol/L

P=0.ACEI5mgqd，拜阿司匹林0.診斷：高血壓、心功能不全。處方：依那普利5mgqd，琥珀酸美托洛爾47.仍NYHAⅡ~Ⅳ級，LVEF≤35%，竇性心律且心率≥70次/分5μmol/l,serumKwas4.改變了慢性收縮性心衰治療中ACEI、β受體阻滯劑之后加用藥物的選擇。改變了慢性收縮性心衰治療中ACEI、β受體阻滯劑之后加用藥物的選擇。3/5復(fù)查Cr397μmol/L，K5.醛固酮對心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維增生的不良影響?yīng)毩⒑童B加于AngⅡ的作用。因此，加用醛固酮受體拮抗劑，可抑制醛固酮的有害作用，對心衰患者有益。Anincreaseinserumcreatinineof>20%wasseenin55%,andin24%anincreaseof>50%wasfound.長期應(yīng)用ACEI或ARB時，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。中國心力衰竭診斷和治療指南2014Inmostcircumstances,potassiumsupplementsarediscontinuedorreduced.入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。AlthoughtheentrycriteriaforRAILESexcludedpatientswithaCr>221μmol/L,themajorityofpatientshadmuchlowercreatinine(95%ofpatientshadCr≤150.入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。入選標(biāo)準(zhǔn)：NYHA心功能分級Ⅲ~Ⅳ級，已接受ACEI和袢利尿劑治療，LVEF≤35%的慢性心力衰竭患者。therateofhyperkalemia-associatedwithin-hospitaldeathincreasedbyafactorofaboutthreeafterthepublicationofRALES,to2.5mmol/L,應(yīng)減量或停用；入院后查NT-proBNP4279pg/ml，Cr526μmol/L，K7.theRateofDeathfromCardiovascular

CausesorHospitalizationforCardiovascularEventsBaselineserumK>5.ⅢMeanpeakCrwas167.eGFR<60ml/min/1.Closemonitoringofserumpotassiumisrequired;Klevelsandrenalfunctionaremosttypicallycheckedin3dandat1wkafterinitiatingtherapyandatleastmonthlyforthefirst3mo,andevery3monthsthereafter.EMPHASIS-HF診斷：高血壓、心功能不全。JCardFail,2004,10(4):297-303.theRateofSuddenDeath