醛固酮受體拮抗劑在心力衰竭的應(yīng)用優(yōu)選課件

1、Aldosterone receptor antagonists (mineralocorticoid receptor antagonises)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(xiàng)。Aldosterone receptor antagonis作用機(jī)理 醛固酮對(duì)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Ang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(zhǎng)期應(yīng)用ACEI或ARB時(shí)，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

2、固酮的有害作用，對(duì)心衰患者有益。作用機(jī)理 醛固酮對(duì)心肌重構(gòu)，特別是心肌細(xì)胞外基質(zhì)促進(jìn)纖維入選標(biāo)準(zhǔn)：NYHA心功能分級(jí)級(jí)，已接受ACEI和袢利尿劑治療，LVEF35%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 221 mol/L, K 5 mmol/L。RALES入選標(biāo)準(zhǔn)：NYHA心功能分級(jí)級(jí)，已接受ACEI和袢利尿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(jí)級(jí)3（0.4%）4（0.5%） 581（69%）592（72%） 257（31%）226（27%）LVEF(%)25.26.825.66.7藥物：袢利尿劑100%100% ACEI94%9

3、5%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基線臨床特征臨床特征安慰劑組（841例）螺內(nèi)酯組（822例）全因死亡率平均隨訪24月全因死亡率亞組分析106 mol/l亞組分析106 mol/l入選標(biāo)準(zhǔn)：AMI后314d, 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 221 mol/L，K 5 mmol/L，應(yīng)用其它潴 鉀利尿劑等。EPHESUS入選標(biāo)準(zhǔn)：AMI后314d, LVEF 40%，伴心衰查體：HR 90 bpm， R 20 bpm，BP 140/90 mm Hg。4

4、mol/L, or GFR 30 mL/min/1.排除標(biāo)準(zhǔn)：原發(fā)病為瓣膜病，UA,等，Cr 221 mol/L, K 5 mmol/L。病例1 住院號(hào)：021782加用速尿 20 mg qd。The mean follow-up period was 11 months.the rate of hyperkalemia-associated with in-hospital death increased by a factor of about three after the publication of RALES, to 2.0 per 1000 by late 2001The rat

5、e of hospitalization for heart failure declined gradually during the study period, with no statistically significant change in this variable after the publication of RALESK 4 mmol/LK 4 mmol/LP=0.Follow-up visits occurred at one and four weeks, three months, and every three months thereafter until th

6、e termination of the study.病例1 住院號(hào)：0217820 per 1000 by late 2001Cr should be 221 mol/L in men or 176.5 mol/l, serum K was 4.因此，加用醛固酮受體拮抗劑，可抑制醛固酮的有害作用，對(duì)心衰患者有益。長(zhǎng)期應(yīng)用ACEI或ARB時(shí)，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。查體：P 88 bpm，R 22 bpm，BP 86/55 mm Hg，雙肺少量濕啰音。AMI后，LVEF 40%，有心衰癥狀或既往有糖尿病史者。97查體：HR 90 bpm， R 20 bpm，BP 140/the

7、 Rate of Death from Any Cause平均隨訪16月the Rate of Death from Any Cauthe Rate of Death from Cardiovascular Causes or Hospitalization for Cardiovascular Eventsthe Rate of Death from Cardiov6 mol/L11.仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分醛固酮受體拮抗劑適應(yīng)癥64歲男性，因“心悸2天”于2014-4-21就診。64歲男性，因“心悸2天”于2014-4-21就診。醛固酮受體拮抗劑能改善慢性收縮

8、性心力衰竭（左心衰竭）患者的預(yù)后。An initial dose of spironolactone of 12.At baseline, Cr levels were 117.8 mol/L in women(or GFR130 ms），已接受ACEI或（和）ARB、受體阻滯劑，6個(gè)月內(nèi)因心血管疾病住院（若無(wú)住院，BNP250 pg/ml,或NT-proBNP500 pg/ml(男），750 pg/ml（女）。Cr should be 221 mol/L in men or 176.5 mol/l, serum K was 4.Although the entry criteria for

9、RAILES excluded patients with a Cr 221 mol/L, the majority of patients had much lower creatinine (95% of patients had Cr 150.Strategies to Minimize the Risk of Hyperkalemia in Patients Treated With Aldosterone Antagonists現(xiàn)在，醛固酮受體拮抗劑是唯一的選擇。改變了慢性收縮性心衰治療中ACEI、 受體阻滯劑之后加用藥物的選擇。病例1 住院號(hào)：021782是繼受體阻滯劑后又一種證實(shí)

10、可顯著降低慢性收縮性心衰患者心臟性猝死且能長(zhǎng)期使用的藥物。ACEIthe rate of hyperkalemia-associated with in-hospital death increased by a factor of about three after the publication of RALES, to 2.平均ACEI劑量（mg/d)the Rate of Sudden Death from Cardiac Causes6 mol/L11.the Rate of SuddeK 4 mmol/LK 4 mmol/LP=0.29Cr 97 mol/LCr 97 mol/LP

11、=0.03亞組分析K 130 ms），已接受ACEI或（和）ARB、受體阻滯劑，6個(gè)月內(nèi)因心血管疾病住院（若無(wú)住院，BNP250 pg/ml,或NT-proBNP500 pg/ml(男），750 pg/ml（女）。排除標(biāo)準(zhǔn)：AMI， NYHA心功能分級(jí)級(jí)、級(jí)，K 5 mmol/L，eGFR 30 ml/min/1.73m2。EMPHASIS-HF入選標(biāo)準(zhǔn)： 55歲，NYHA心功能分級(jí)級(jí)，LVEF30100.8100.8平均隨訪21月平均隨訪21月醛固酮受體拮抗劑在心力衰竭的應(yīng)用優(yōu)選課件醛固酮受體拮抗劑在心力衰竭的應(yīng)用優(yōu)選課件醛固酮受體拮抗劑在心力衰竭的應(yīng)用優(yōu)選課件eGFR 60ml/min/1

12、.73m2 60ml/min/1.73m2eGFR 60ml/min/1.73m2醛固酮受體拮抗劑適應(yīng)癥LVEF35%、NYHA級(jí)的患者；已使用ACEI（或ARB）和受體阻滯劑治療，仍持續(xù)有癥狀的患者（類，A級(jí)）AMI后，LVEF 40%，有心衰癥狀或既往有糖尿病史者。 中國(guó)心力衰竭診斷和治療指南2014醛固酮受體拮抗劑適應(yīng)癥LVEF35%、NYHA級(jí)的患 慢性收縮性心衰的基本治療方案從“黃金搭檔”（ACEI加受體阻滯劑）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、受體阻滯劑之后又一個(gè)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

13、衰治療中ACEI、 受體阻滯劑之后加用藥物的選擇。過(guò)去存在多種選擇，包括ARB、地高辛等。現(xiàn)在，醛固酮受體拮抗劑是唯一的選擇。是繼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(zhǎng)期使用的藥物。 慢性收縮性心衰的基本治療方案從“黃金搭檔”（ACEI醛固酮受體拮抗劑適應(yīng)癥12/5癥狀緩解出院。慢性收縮性心衰的基本治療方案從“黃金搭檔”（ACEI加受體阻滯劑）轉(zhuǎn)變?yōu)椤敖鹑恰保ㄇ皟烧呒尤┕掏荏w拮抗劑）加用速尿 20 mg qd。6 mol/L11.Mean peak Cr was 167.6 mol/L11.5 mol/l, serum K was 4.4/5下午請(qǐng)我科會(huì)診后停用

14、螺內(nèi)酯。仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分加用速尿 20 mg qd。NYHA心功能分級(jí)級(jí)Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients wi

15、th heart failure with preserved ejection fraction.若起始用藥后血K升高6 mmol/L或出現(xiàn)腎功能惡化，則不加量直至血K 5 mmol/L), with 10% having serum K 6 m mol/L. An increase in serum creatinine of 20% was seen in 55%, and in 24% an increase of 50% was found.Svensson M, et al.J Card Fail,RAILES METHODS Patients criteria for exclu

16、sion were a serum Cr 221 mol/L or K 5.0 mmol/L. Follow-up measurements of serum K, were conducted every 4 weeks for the first 12 weeks, then every 3 months for up to 1 year and every 6 months thereafter until the end of the study .Study medication could be withheld in the event of serious hyperkalem

17、ia, a serum Cr 354 mol/L.Although the entry criteria for RAILES excluded patients with a Cr 221 mol/L, the majority of patients had much lower creatinine (95% of patients had Cr 150.3 mol/L ）RAILES METHODS Patients EPHESUSExclusion: serum Cr 221 mol/L or K 5.0 mmol/L. Follow-up visits occurred at on

18、e and four weeks, three months, and every three months thereafter until the termination of the study. The serum potassium concentration was measured 48 hours after the initiation of treatment, at one, four, and five weeks, at all scheduled study visits, and within one week after any change of dose.E

19、PHESUSExclusion: serum Cr Cr should be 221 mol/L in men or 176.8 umol/L in women (or eGFR 30 mL/min/1.73 m2), and K should be 5.0 mmol/L. Careful monitoring of K, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia an

20、d renal insufficiency. (CLASS I, Levelof Evidence: A) Cr should be 221 mol/L in Aldosterone receptor antagonists are recommended to Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency when serum creatinine is 22

21、1 mol/L in men or 176.8 mol/L in women(or GFR5.0 mmol/L. (CLASS Level of Evidence: B)Aldosterone receptor antagonis若起始用藥后血K升高6 mmol/L或出現(xiàn)腎功能惡化，則不加量直至血K 221 mol/L, the majority of patients had much lower creatinine (95% of patients had Cr 150.仍NYHA級(jí)， LVEF 35%4 mol/L, or GFR 30 mL/min/1.從小劑量起始，逐漸加量，尤其螺

22、內(nèi)酯不推薦大劑量。Close monitoring of serum potassium is required; K levels and renal function are most typically checked in 3 d and at 1 wk after initiating therapy and at least monthly for the first 3 mo, and every 3 months thereafter.平均ACEI劑量（mg/d)Conclusions and Relevance In this randomized controlled tr

23、ial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction.因此，加用醛固酮受體拮抗劑，可抑制醛固酮的有害作用，對(duì)心衰患者有益。長(zhǎng)期應(yīng)用ACEI或ARB時(shí)，起始醛固酮降低，隨后即出現(xiàn)“逃

24、逸現(xiàn)象”。5 mol/l, serum K was 4.Careful monitoring of K, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency.適用于LVEF35%、NYHA級(jí)的患者；Cr should be 221 mol/L in men or 176.(CLASS Level of Evidence: B)入選標(biāo)

25、準(zhǔn)：NYHA心功能分級(jí)級(jí)，已接受ACEI和袢利尿劑治療，LVEF35%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 221 mol/L, K 5 mmol/L。慢性HF-REF(NYHA級(jí)）藥物治療流程At baseline, Cr levels were 117.An initial dose of spironolactone of 12.Strategies to Minimize the Risk of Hyperkalemia in Patients Treated With Aldosterone AntagonistsThe risk of hyperkalemi

26、a increases progressively when Cr is141.4 mol/L, or GFR 30 mL/min/1.73 m2.Baseline serum K5.0 mmol/L.An initial dose of spironolactone of 12.5 mg or eplerenone 25 mg is typical.The risk of hyperkalemia is increased with concomitant use of higher doses of ACE inhibitors (captopril75 mg daily; enalapr

27、il or lisinopril10 mg daily).In most circumstances, potassium supplements are discontinued or reduced. Close monitoring of serum potassium is required; K levels and renal function are most typically checked in 3 d and at 1 wk after initiating therapy and at least monthly for the first 3 mo, and ever

28、y 3 months thereafter.NYHA心功能分級(jí)級(jí)Strategies to MinimConclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with h

29、eart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations. 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)。Conclusions and Relevance In 病

30、例1 住院號(hào)：021782 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。有“高血壓”病史10余年，服藥治療，血壓控制不詳。查體：P 88 bpm，R 22 bpm，BP 86/55 mm Hg，雙肺少量濕啰音。雙下肢無(wú)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-proBNP4279 pg/ml，Cr 526 mol/L ，K 7.18 mmol/L（2/5）。3/5醫(yī)囑：螺內(nèi)酯40 mg bid，速尿20 mg qd。3/5復(fù)查Cr 397 mol/L ，K 5.4 mmol/L。4/5下午請(qǐng)我科會(huì)診后停用螺

31、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(dòng)脈和冠狀動(dòng)脈硬化。12/5癥狀緩解出院。2013-1-28 UCG：老年退行性瓣膜病，二尖瓣、主動(dòng)脈瓣、三尖瓣輕度關(guān)閉不全，LVEF 78%(正常值5480%）。病例1 住院號(hào)：021782 79歲女性，病例2（門(mén)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(dòng)”病史。查體：HR 90 bpm， R 20 bpm，BP 140/90 mm Hg。診斷：冠心病、高血壓。處方：依那普利 5 mg qd，琥珀酸美托洛爾 47.5 mg qd，拜阿司匹林 0.1 qd，螺內(nèi)酯 20 mg qd。25/

32、4復(fù)診，出現(xiàn)活動(dòng)后氣促，雙下肢浮腫。診斷：高血壓、心功能不全。加用速尿 20 mg qd。病例2（門(mén)診患者） 64歲男性，因“心悸2天”于201有充血癥狀/體征無(wú)充血癥狀/體征利尿劑+ACEI(或ARB）+受體阻滯劑ACEI(或ARB）+受體阻滯劑仍NYHA級(jí)， LVEF 35%加醛固酮受體拮抗劑仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分仍為NYHA級(jí)，LVEF45%加伊伐布雷定加地高辛慢性HF-REF(NYHA級(jí)）藥物治療流程有充血癥狀/體征無(wú)充血癥狀/體征利尿劑+ACEI(或ARB）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LVEF35%、NYH

33、A級(jí)的患者；已使用ACEI（或ARB）和受體阻滯劑治療，仍持續(xù)有癥狀的患者（類，A級(jí)）；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 5 mmol/L,腎功能受損（Cr 221 mol/L，或eGFR 5.5 mmol/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。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）患者謝謝謝謝病例1 住院號(hào)：021782仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分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。AMI后，LVEF 40%，有心衰癥狀或既往有糖尿病史

34、者。ACEI(或ARB）+受體阻滯劑平均ACEI劑量（mg/d)排除標(biāo)準(zhǔn)：AMI， NYHA心功能分級(jí)級(jí)、級(jí)，K 5 mmol/L，eGFR 30 ml/min/1.平均ACEI劑量（mg/d)Cr should be 221 mol/L in men or 176.仍NYHA級(jí)， LVEF 35%12/5癥狀緩解出院。入選標(biāo)準(zhǔn)：AMI后314d, LVEF 40%，伴心衰相關(guān)的肺 部濕啰音、胸片提示肺水腫、S3；從小劑量起始，逐漸加量，尤其螺內(nèi)酯不推薦大劑量。適用于LVEF35%、NYHA級(jí)的患者；Strategies to Minimize the Risk of Hyperkalemia

35、 in Patients Treated With Aldosterone AntagonistsNYHA心功能分級(jí)級(jí)Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patient

36、s with heart failure with preserved ejection fraction.Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients wit

37、h heart failure with preserved ejection fraction.若起始用藥后血K升高6 mmol/L或出現(xiàn)腎功能惡化，則不加量直至血K 221 mol/L, K 5 mmol/L。RALES入選標(biāo)準(zhǔn)：NYHA心功能分級(jí)級(jí)，已接受ACEI和袢利尿亞組分析106 mol/l亞組分析106 mol/l醛固酮受體拮抗劑在心力衰竭的應(yīng)用優(yōu)選課件醛固酮受體拮抗劑應(yīng)用注意事項(xiàng)醛固酮受體拮抗劑應(yīng)用注意事項(xiàng)the rate of hyperkalemia-associated with in-hospital death increased by a factor of abo

38、ut three after the publication of RALES, to 2.0 per 1000 by late 2001 the rate of hyperkalemia-assocEPHESUSExclusion: serum Cr 221 mol/L or K 5.0 mmol/L. Follow-up visits occurred at one and four weeks, three months, and every three months thereafter until the termination of the study. The serum pot

39、assium concentration was measured 48 hours after the initiation of treatment, at one, four, and five weeks, at all scheduled study visits, and within one week after any change of dose.EPHESUSExclusion: serum CrNYHA心功能分級(jí)級(jí)定期檢測(cè)血鉀和腎功能，如血鉀 5.入選標(biāo)準(zhǔn)：NYHA心功能分級(jí)級(jí)，已接受ACEI和袢利尿劑治療，LVEF35%的慢性心力衰竭患者。12/5胸部CT：慢支、肺氣腫

40、，兩肺支擴(kuò)并感染，心臟增大，主動(dòng)脈和冠狀動(dòng)脈硬化。仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分ACEI5 mol/l, serum K was 4.Close monitoring of serum potassium is required; K levels and renal function are most typically checked in 3 d and at 1 wk after initiating therapy and at least monthly for the first 3 mo, and every 3 months thereafter.長(zhǎng)期

41、應(yīng)用ACEI或ARB時(shí)，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。排除標(biāo)準(zhǔn)：原發(fā)病為瓣膜病，UA,等，Cr 221 mol/L, K 5 mmol/L。73 m2), and K should be 5.診斷：冠心病、高血壓。醛固酮受體拮抗劑適應(yīng)癥仍NYHA級(jí)，LVEF35%，竇性心律且心率70次/分K 221 mol/L or K 5.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)。the Rate of Death from Any Cause中國(guó)心力衰竭診斷和治療指南2014仍NYHA級(jí)， LVEF 35%5 m

42、ol/l, serum K was 4.Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved eje

43、ction fraction.若起始用藥后血K升高6 mmol/L或出現(xiàn)腎功能惡化，則不加量直至血K 5 mmol/l。K 5 mmol/L，eGFR 5 mmol/L,腎功能受損（Cr 221 mol/L，或eGFR 5 mmol/L), with 10% having serum K 6 m mol/L.4/5下午請(qǐng)我科會(huì)診后停用螺內(nèi)酯。125 patients with were LVEF 45%.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。4 mol/L, or GFR 30 mL/min/1.長(zhǎng)期應(yīng)用ACEI或ARB時(shí)，起始醛固酮降低，隨后即出現(xiàn)“逃逸現(xiàn)象”。the Rate of Sudden Death from Cardiac CausesWhether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger popula