醛固酮受体拮抗剂在心力衰竭的应用ppt培训课程课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2021/2/28,#,Aldosterone receptor antagonists (mineralocorticoid receptor antagonises),RALES,、,EPHESUS,、,EMPHASIS-HF,试验奠定了醛固酮受体拮抗剂在慢性收缩性心力衰竭的地位。,醛固酮受体拮抗剂应用的注意事项。,Aldosterone receptor antagonis,1,作用机理,醛固酮对,心肌重构,，特别是心肌细胞外基质,促进纤维增生,的不良影响独立和叠加于,Ang,的作用。衰竭心脏心室醛固酮生成及活化增加，且与心衰严重程度成正比。长期应用,ACEI,或,ARB,时，起始醛固酮降低，随后即出现“,逃逸现象,”。因此，加用醛固酮受体拮抗剂，可抑制醛固酮的有害作用，对心衰患者有益。,作用机理 醛固酮对心肌重构，特别是心肌细胞外基质促进纤维,2,入选标准：,NYHA,心功能分级,级，已接受,ACEI,和袢利尿剂治疗，,LVEF35%,的慢性心力衰竭患者。,排除标准：,原发病为瓣膜病，,UA,等，,Cr 221,mol/L, K 5 mmol/L,。,RALES,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿,3,基线临床特征,临床特征,安慰剂组（,841,例）,螺内酯组（,822,例）,NYHA,心功能分级,级,3,（,0.4%,）,4,（,0.5%,）,581,（,69%,）,592,（,72%,）,257,（,31%,）,226,（,27%,）,LVEF(%),25.26.8,25.66.7,药物：袢利尿剂,100%,100%,ACEI,94%,95%,平均,ACEI,剂量（,mg/d),卡托普利,62.1,63.4,依那普利,16.5,13.5,福辛普利,13.1,15.5,基线临床特征临床特征安慰剂组（841例）螺内酯组（822例）,4,全因死亡率,平均随访,24,月,全因死亡率,5,亚组分析,106 mol/l,亚组分析106 mol/l,6,入选标准：,AMI,后,314d, LVEF 40%,，,伴心衰相关的肺,部湿啰音、胸片提示肺水肿、,S3,；或合并糖尿病。,排除标准：,Cr 221,mol/L,，,K 5 mmol/L,，应用其它潴,钾利尿剂等。,EPHESUS,入选标准：AMI后314d, LVEF 40%，伴心衰,7,97,97,8,the Rate of Death from Any Cause,平均随访,16,月,the Rate of Death from Any Cau,9,the Rate of Death from,Cardiovascular Causes or Hospitalization for Cardiovascular Events,the Rate of Death from Cardiov,10,the Rate of Sudden Death from Cardiac Causes,the Rate of Sudden Death from,11,长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。,At baseline, Cr levels were 117.,J Card Fail, 2004, 10(4):297-303.,醛固酮受体拮抗剂适应症,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.,K 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 141.,利尿剂+ACEI(或ARB）+受体阻滞剂,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.,K 4 mmol/LK 4 mmol/L,P,=0.29Cr 130 ms,），已接受,ACEI,或（和）,ARB,、,受体阻滞剂，,6,个月内因心血管疾病住院（若无住院，,BNP250 pg/ml,或,NT-proBNP500 pg/ml,(,男），,750 pg/ml,（女）。,排除标准：,AMI,，,NYHA,心功能分级,级、,级，,K 5 mmol/L,，,eGFR 30 ml/min/1.73m,2,。,EMPHASIS-HF,入选标准： 55岁，NYHA心功能分级级，LVEF30,13,100.8,100.8,14,平均随访,21,月,平均随访21月,15,醛固酮受体拮抗剂在心力衰竭的应用ppt培训课程课件,16,醛固酮受体拮抗剂在心力衰竭的应用ppt培训课程课件,17,醛固酮受体拮抗剂在心力衰竭的应用ppt培训课程课件,18,eGFR 60ml/min/1.73m,2,60ml/min/1.73m,2,eGFR 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 5.,长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。,Aldosterone receptor antagonists (mineralocorticoid receptor antagonises),是继受体阻滞剂后又一种证实可显著降低慢性收缩性心衰患者心脏性猝死且能长期使用的药物。,J Card Fail, 2004, 10(4):297-303.,醛固酮对心肌重构，特别是心肌细胞外基质促进纤维增生的不良影响独立和叠加于Ang的作用。,有“高血压”病史10余年，服药治疗，血压控制不详。,(CLASS Level of Evidence: B),Aldosterone receptor antagonists (mineralocorticoid receptor antagonises),适用于LVEF35%、NYHA级的患者；,仍NYHA级， LVEF 35%,6 mol/L11.,入选标准：AMI后314d, LVEF 40%，伴心衰相关的肺 部湿啰音、胸片提示肺水肿、S3；,3/5医嘱：螺内酯40 mg bid，速尿20 mg qd。,诊断：高血压、心功能不全。,Close monitoring of serum pota,23,After the publication of RALES, however,the rate of prescriptions for this drug,increased by a factor of about,five, to 149 per 1000 by late 2001,After the publication of RALES,24,The rate of hospital admission for hyperkalemia,increased by a factor of about,three,after the publication of RALES, to 11.0 per 1000 by late 2001,The rate of hospital admission,25,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 2001,the rate of hyperkalemia-assoc,26,The rate of hospitalization for heart failure,declined gradually during the study period, with no statistically significant change in this variable after the publication of RALES,The rate of hospitalization fo,27,Svensson M, et al.J Card Fail, 2004, 10(4):297-303.,125 patients with were LVEF 45%.,Blood tests were performed,bimonthly,or more frequently if necessary.,At baseline, Cr levels were 117.66.5,mol/l, serum K was 4.20.3 mmol/L. The mean follow-up period was 11 months.,Mean peak Cr was 167.6,mol/L11.9 (45% increase from baseline) , mean peak serum K was 5.00.4 mmol/L (21% increase from baseline). 36% of the patients developed hyperkalemia (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,28,RAILES,METHODS Patients criteria for exclusion 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 hyperkalemia, 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,29,EPHESUS,Exclusion: 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 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.,EPHESUSExclusion: serum Cr,30,Cr,should be ,221,mol/L in men or ,176.8,umol/L in women (or eGFR ,30,mL/min/1.73 m,2,), 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 and renal insufficiency. (CLASS I, Levelof Evidence: A),Cr should be 221 mol/L in,31,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 221,mol/L in men or 176.8,mol/L in women(or GFR5.0 mmol/L. (,CLASS,Level of Evidence: B),Aldosterone receptor antagonis,32,若起始用药后血,K,升高,6 mmol/L,或出现肾功能恶化，则不加量直至血,K 141.4,mol/L, or GFR 30 mL/min/1.73 m,2,.,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; enalapril 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 every,3 months,thereafter.,Strategies to Minimize the Ris,34,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 ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.,醛固酮受体拮抗剂在慢性心力衰竭（原发病为瓣膜病、,LVEF,保留的心力衰竭、慢性右心衰竭）、急性心力衰竭的应用尚缺乏循证医学证据。,Conclusions and Relevance In,35,病例,1,住院号：,021782,79,岁女性，因“反复咳嗽,40,年，气促,10,年，加重,7,天”于,2014-5-2,入院。有“高血压”病史,10,余年，服药治疗，血压控制不详。查体：,P 88 bpm,，,R 22 bpm,，,BP 86/55 mm Hg,，双肺少量湿啰音。双下肢无浮肿。入院诊断,AECOPD,，,慢性肺源性心脏病 失代偿期？高血压，慢性肾功能不全。入院后查,NT-proBNP4279 pg/ml,，,Cr 526,mol/L,，,K 7.18 mmol/L,（,2/5,）。,3/5,医嘱：,螺内酯,40 mg bid,，速尿,20 mg qd,。,3/5,复查,Cr 397,mol/L,，,K 5.4 mmol/L,。,4/5,下午请我科会诊后停用螺内酯。,12/5,胸部,CT,：慢支、肺气肿，两肺支扩并感染，心脏增大，主动脉和冠状动脉硬化。,12/5,症状缓解出院。,2013-1-28 UCG,：老年退行性瓣膜病，二尖瓣、主动脉瓣、三尖瓣轻度关闭不全，,LVEF 78%(,正常值,5480%,）。,病例1 住院号：021782 79岁女性，,36,the Rate of Sudden Death from Cardiac Causes,改变了慢性收缩性心衰治疗中ACEI、 受体阻滞剂之后加用药物的选择。,为避免高钾血症和肾功能损害，血钾 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 20% was seen in 55%, and in 24% an increase of 50% was found.,8 mol/L in women(or GFR,5,mmol/L,肾功能受损（,Cr 221,mol/L,，或,eGFR 5.5 mmol/L,应,减量或停用；从,小剂量起始,，逐渐加量，尤其螺内酯不推荐大剂量。,小结醛固酮受体拮抗剂能改善慢性收缩性心力衰竭（左心衰竭）患者,39,谢谢,谢谢,40,作用机理,醛固酮对,心肌重构,，特别是心肌细胞外基质,促进纤维增生,的不良影响独立和叠加于,Ang,的作用。衰竭心脏心室醛固酮生成及活化增加，且与心衰严重程度成正比。长期应用,ACEI,或,ARB,时，起始醛固酮降低，随后即出现“,逃逸现象,”。因此，加用醛固酮受体拮抗剂，可抑制醛固酮的有害作用，对心衰患者有益。,作用机理 醛固酮对心肌重构，特别是心肌细胞外基质促进纤维,41,入选标准：,NYHA,心功能分级,级，已接受,ACEI,和袢利尿剂治疗，,LVEF35%,的慢性心力衰竭患者。,排除标准：,原发病为瓣膜病，,UA,等，,Cr 221,mol/L, K 5 mmol/L,。,RALES,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿,42,亚组分析,106 mol/l,亚组分析106 mol/l,43,醛固酮受体拮抗剂在心力衰竭的应用ppt培训课程课件,44,醛固酮受体拮抗剂,应用注意事项,醛固酮受体拮抗剂应用注意事项,45,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 2001,the rate of hyperkalemia-assoc,46,AMI后，LVEF 40%，有心衰症状或既往有糖尿病史者。,12/5胸部CT：慢支、肺气肿，两肺支扩并感染，心脏增大，主动脉和冠状动脉硬化。,The rate of hospitalization for heart failure declined gradually during the study period, with no statistically significant change in this variable after the publication of RALES,已使用ACEI（或ARB）和受体阻滞剂治疗，仍持续有症状的患者（类，A级）；,J Card Fail, 2004, 10(4):297-303.,醛固酮对心肌重构，特别是心肌细胞外基质促进纤维增生的不良影响独立和叠加于Ang的作用。,入院后查NT-proBNP4279 pg/ml，Cr 526 mol/L ，K 7.,查体：HR 90 bpm， R 20 bpm，BP 140/90 mm Hg。,适用于LVEF35%、NYHA级的患者；,12/5胸部CT：慢支、肺气肿，两肺支扩并感染，心脏增大，主动脉和冠状动脉硬化。,73 m-2）不宜应用。,ACEI,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。, 60ml/min/1.,EMPHASIS-HF,79岁女性，因“反复咳嗽40年，气促10年，加重7天”于2014-5-2入院。,长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。,After the publication of RALES, however, the rate of prescriptions for this drug increased by a factor of about five, to 149 per 1000 by late 2001,有“高血压”病史10余年，服药治疗，血压控制不详。,利尿剂+ACEI(或ARB）+受体阻滞剂,醛固酮受体拮抗剂能改善慢性收缩性心力衰竭（左心衰竭）患者的预后。,EPHESUS,Exclusion: 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 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.,AMI后，LVEF 40%，有心衰症状或既往有糖尿病史者,47,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.,K 20% was seen in 55%, and in 24% an increase of 50% was found.,长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。,中国心力衰竭诊断和治疗指南2014,In most circumstances, potassium supplements are discontinued or reduced.,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。,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.,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。,the rate of hyperkalemia-associated with in-hospital death increased by a factor of about three after the publication of RALES, to 2.,5 mmol/L,应减量或停用；,入院后查NT-proBNP4279 pg/ml，Cr 526 mol/L ，K 7.,the Rate of Death from Cardiovascular Causes or Hospitalization for Cardiovascular Events,Baseline serum K5.,Mean peak Cr was 167.,eGFR 60ml/min/1.,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.,EMPHASIS-HF,诊断：高血压、心功能不全。,J Card Fail, 2004, 10(4):297-303.,the Rate of Sudden Death from Cardiac Causes,长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。,Study medication could be withheld in the event of serious hyperkalemia, a serum Cr 354 mol/L.,Follow-up visits occurred at one and four weeks, three months, and every three months thereafter until the termination of the study.,若起始用药后血K升高6 mmol/L或出现肾功能恶化，则不加量直至血K 5 mmol/l。,有“冠心病、心房颤动”病史。,18 mmol/L（2/5）。,中国心力衰竭诊断和治疗指南2014,25/4复诊，出现活动后气促，双下肢浮肿。,醛固酮受体拮抗剂在慢性心力衰竭（原发病为瓣膜病、LVEF保留的心力衰竭、慢性右心衰竭）、急性心力衰竭的应用尚缺乏循证医学证据。,8 mol/L in women(or GFR 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 221 mol/L, K 5 mmol/L。,12/5胸部CT：慢支、肺气肿，两肺支扩并感染，心脏增大，主动脉和冠状动脉硬化。,73 m-2）不宜应用。,RAILES METHODS Patients criteria for exclusion were a serum Cr 221 mol/L or K 5.,Follow-up visits occurred at one and four weeks, three months, and every three months thereafter until the termination of the study.,查体：HR 90 bpm， R 20 bpm，BP 140/90 mm Hg。,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.,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。,Baseline serum K5.,若起始用药后血,K,升高,6 mmol/L,或出现肾功能恶化，则不加量直至血,K 5 mmol/l,。确定高钾血症或肾功能不全去除后,72h,可考虑减量再使用。,The serum potassium concentrat,48,