醛固酮受体拮抗剂在心力衰竭的应用优选课件

Aldosterone receptor antagonists(mineralocorticoid receptor antagonises)uRALES、EPHESUS、EMPHASIS-HF试验奠定了醛固酮受体拮抗剂在慢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。性收缩性心力衰竭的地位。u醛固酮受体拮抗剂应用的注意事项。醛固酮受体拮抗剂应用的注意事项。Aldosterone receptor antagonis1作用机理作用机理 醛固酮对醛固酮对心肌重构心肌重构，特别是心肌细胞，特别是心肌细胞外基质外基质促进纤维增生促进纤维增生的不良影响独立的不良影响独立和叠加于和叠加于Ang的作用。衰竭心脏心室的作用。衰竭心脏心室醛固酮生成及活化增加，且与心衰严醛固酮生成及活化增加，且与心衰严重程度成正比。长期应用重程度成正比。长期应用ACEIACEI或或ARBARB时，时，起始醛固酮降低，随后即出现起始醛固酮降低，随后即出现“逃逸逃逸现象现象”。因此，加用醛固酮受体拮抗。因此，加用醛固酮受体拮抗剂，可抑制醛固酮的有害作用，对心剂，可抑制醛固酮的有害作用，对心衰患者有益。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：入选标准：NYHA心功能分级心功能分级级，已接受级，已接受ACEI和袢利尿剂治疗，和袢利尿剂治疗，LVEF35%的慢性心力衰的慢性心力衰竭患者。竭患者。排除标准：排除标准：原发病为瓣膜病，原发病为瓣膜病，UA,等，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床特征安慰安慰剂组（841例）例）螺内螺内酯组（822例）例）NYHA心功能分心功能分级级级3（0.4%）4（0.5%）581（69%）592（72%）257（31%）226（27%）LVEF(%)25.26.825.66.7药物：袢利尿物：袢利尿剂100%100%ACEI94%95%平均平均ACEI剂量（量（mg/d)卡托普利卡托普利62.163.4 依那普利依那普利16.513.5 福辛普利福辛普利13.115.5基线临床特征临床特征安慰剂组（841例）螺内酯组（822例）4全因死亡率全因死亡率平均随访平均随访24月月全因死亡率5亚组分析亚组分析106 mol/l亚组分析106 mol/l6入选标准：入选标准：AMI后后314d,LVEF 40%，伴心衰相关的肺伴心衰相关的肺 部湿啰音、胸片提示肺水肿、部湿啰音、胸片提示肺水肿、S3；或合并糖尿病。；或合并糖尿病。排除标准：排除标准：Cr 221 mol/L，K 5 mmol/L，应用其它潴，应用其它潴 钾利尿剂等。钾利尿剂等。EPHESUS入选标准：AMI后314d,LVEF 40%，伴心衰7查体：HR 90 bpm，R 20 bpm，BP 140/90 mm Hg。4 mol/L,or GFR 30 mL/min/1.排除标准：原发病为瓣膜病，UA,等，Cr 221 mol/L,K 5 mmol/L。病例1 住院号：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 rate 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 the termination of the study.病例1 住院号：0217820 per 1000 by late 2001Cr should be 221 mol/L in men or 176.5 mol/l,serum K was 4.因此，加用醛固酮受体拮抗剂，可抑制醛固酮的有害作用，对心衰患者有益。长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。查体：P 88 bpm，R 22 bpm，BP 86/55 mm Hg，双肺少量湿啰音。AMI后，LVEF 40%，有心衰症状或既往有糖尿病史者。97查体：HR 90 bpm，R 20 bpm，BP 140/8the Rate of Death from Any Cause平均随访平均随访16月月the Rate of Death from Any Cau9the Rate of Death from Cardiovascular Causes or Hospitalization for Cardiovascular Eventsthe Rate of Death from Cardiov106 mol/L11.仍NYHA级，LVEF35%，窦性心律且心率70次/分醛固酮受体拮抗剂适应症64岁男性，因“心悸2天”于2014-4-21就诊。64岁男性，因“心悸2天”于2014-4-21就诊。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。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）。Cr should be 221 mol/L in men or 176.5 mol/l,serum K was 4.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.Strategies to Minimize the Risk of Hyperkalemia in Patients Treated With Aldosterone Antagonists现在，醛固酮受体拮抗剂是唯一的选择。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。病例1 住院号：021782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。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剂量（mg/d)the Rate of Sudden Death from Cardiac Causes6 mol/L11.the Rate of Sudde11K 4 mmol/LK 4 mmol/LP=0.29Cr 97 mol/LCr 97 mol/LP=0.03亚组分析亚组分析K 130 ms），已接），已接受受ACEI或（和）或（和）ARB、受体阻滞剂，受体阻滞剂，6个月内因心个月内因心血管疾病住院（若无住院，血管疾病住院（若无住院，BNP250 pg/ml,或或NT-proBNP500 pg/ml(男），男），750 pg/ml（女）。（女）。排除标准：排除标准：AMI，NYHA心功能分级心功能分级级、级、级，级，K 5 mmol/L，eGFR 30 ml/min/1.73m2。EMPHASIS-HF入选标准：55岁，NYHA心功能分级级，LVEF3013100.8100.814平均随访平均随访21月月平均随访21月15醛固酮受体拮抗剂在心力衰竭的应用优选课件16醛固酮受体拮抗剂在心力衰竭的应用优选课件17醛固酮受体拮抗剂在心力衰竭的应用优选课件18eGFR 60ml/min/1.73m2 60ml/min/1.73m2eGFR 60ml/min/1.73m219醛固酮受体拮抗剂适应症uLVEF35%、NYHA级的患者；已使级的患者；已使用用ACEI（或（或ARB）和）和受体阻滞剂治疗，受体阻滞剂治疗，仍持续有症状的患者（仍持续有症状的患者（类，类，A级）级）uAMI后，后，LVEF 40%，有心衰症状或既往，有心衰症状或既往有糖尿病史者。有糖尿病史者。中国心力衰竭诊断和治疗指南中国心力衰竭诊断和治疗指南2014醛固酮受体拮抗剂适应症LVEF35%、NYHA级的患20 慢性收缩性心衰的基本治疗方案从慢性收缩性心衰的基本治疗方案从“黄金黄金搭档搭档”（ACEI加加受体阻滞剂）转变为受体阻滞剂）转变为“金三金三角角”（前两者加醛固酮受体拮抗剂）（前两者加醛固酮受体拮抗剂）u醛固酮受体拮抗剂是继醛固酮受体拮抗剂是继ACEI、受体阻滞受体阻滞剂之后又一个可以应用于所有伴症状的慢剂之后又一个可以应用于所有伴症状的慢性收缩性心衰患者，并可改善患者的预后。性收缩性心衰患者，并可改善患者的预后。u改变了慢性收缩性心衰治疗中改变了慢性收缩性心衰治疗中ACEI、受受体阻滞剂之后加用药物的选择。过去存在体阻滞剂之后加用药物的选择。过去存在多种选择，包括多种选择，包括ARB、地高辛等。现在，、地高辛等。现在，醛固酮受体拮抗剂是唯一的选择。醛固酮受体拮抗剂是唯一的选择。u是继是继受体阻滞剂后又一种证实可显著降低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慢性收缩性心衰患者心脏性猝死且能长期使用的药物。使用的药物。慢性收缩性心衰的基本治疗方案从“黄金搭档”（ACEI21醛固酮受体拮抗剂适应症12/5症状缓解出院。慢性收缩性心衰的基本治疗方案从“黄金搭档”（ACEI加受体阻滞剂）转变为“金三角”（前两者加醛固酮受体拮抗剂）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下午请我科会诊后停用螺内酯。仍NYHA级，LVEF35%，窦性心律且心率70次/分加用速尿 20 mg qd。NYHA心功能分级级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.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),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,28RAILES 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 29EPHESUSExclusion: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 Cr30 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 and renal insufficiency.(CLASS I,Levelof Evidence:A)Cr should be 221 mol/L in 31uAldosterone 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 antagonis32若起始用药后血若起始用药后血K升高升高6 mmol/L或出现肾功能恶化，或出现肾功能恶化，则不加量直至血则不加量直至血K 221 mol/L,the majority of patients had much lower creatinine(95%of patients had Cr 150.仍NYHA级，LVEF 35%4 mol/L,or GFR 30 mL/min/1.从小剂量起始，逐渐加量，尤其螺内酯不推荐大剂量。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剂量（mg/d)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.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。长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。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.适用于LVEF35%、NYHA级的患者；Cr should be 221 mol/L in men or 176.(CLASS Level of Evidence:B)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。慢性HF-REF(NYHA级）药物治疗流程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 AntagonistsuThe risk of hyperkalemia increases progressively when Cr is141.4 mol/L,or GFR 30 mL/min/1.73 m2.uBaseline serum K5.0 mmol/L.uAn initial dose of spironolactone of 12.5 mg or eplerenone 25 mg is typical.uThe risk of hyperkalemia is increased with concomitant use of higher doses of ACE inhibitors(captopril75 mg daily;enalapril or lisinopril10 mg daily).uIn most circumstances,potassium supplements are discontinued or reduced.u 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.NYHA心功能分级级Strategies to Minim34Conclusions 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（原发醛固酮受体拮抗剂在慢性心力衰竭（原发病为瓣膜病、病为瓣膜病、LVEFLVEF保留的心力衰竭、慢性右心保留的心力衰竭、慢性右心衰竭）、急性心力衰竭的应用尚缺乏循证医学衰竭）、急性心力衰竭的应用尚缺乏循证医学证据。证据。Conclusions and Relevance In 35病例病例1 住院号：住院号：021782 79岁女性，因岁女性，因“反复咳嗽反复咳嗽40年，气促年，气促10年，加年，加重重7天天”于于2014-5-2入院。有入院。有“高血压高血压”病史病史10余余年，服药治疗，血压控制不详。查体：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。，双肺少量湿啰音。双下肢无浮肿。入院诊断双下肢无浮肿。入院诊断AECOPD，慢性肺源性慢性肺源性心脏病心脏病 失代偿期？高血压，慢性肾功能不全。入失代偿期？高血压，慢性肾功能不全。入院后查院后查NT-proBNP4279 pg/ml，Cr 526 mol/L，K 7.18 mmol/L（2/5）。）。3/5医嘱：医嘱：螺内酯螺内酯40 mg bid，速尿，速尿20 mg qd。3/5复查复查Cr 397 mol/L，K 5.4 mmol/L。4/5下午请我科会诊后停用螺内酯。下午请我科会诊后停用螺内酯。12/5胸部胸部CT：慢支、肺气肿，两肺支扩并感染，：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。心脏增大，主动脉和冠状动脉硬化。12/5症状缓症状缓解出院。解出院。2013-1-28 UCG：老年退行性瓣膜病，：老年退行性瓣膜病，二尖瓣、主动脉瓣、三尖瓣轻度关闭不全，二尖瓣、主动脉瓣、三尖瓣轻度关闭不全，LVEF 78%(正常值正常值5480%）。）。病例1 住院号：021782 79岁女性，36病例病例2（门诊患者）（门诊患者）64岁男性，因岁男性，因“心悸心悸2天天”于于2014-4-21就诊。就诊。有有“冠心病、心房颤动冠心病、心房颤动”病史。查体：病史。查体：HR 90 bpm，R 20 bpm，BP 140/90 mm Hg。诊断：诊断：冠心病、高血压冠心病、高血压。处方：依那普利。处方：依那普利 5 mg qd，琥珀酸美托洛尔，琥珀酸美托洛尔 47.5 mg qd，拜阿，拜阿司匹林司匹林 0.1 qd，螺内酯螺内酯 20 mg qd。25/4复诊，复诊，出现活动后气促，双下肢浮肿。诊断：高出现活动后气促，双下肢浮肿。诊断：高血压、心功能不全。加用速尿血压、心功能不全。加用速尿 20 mg qd。病例2（门诊患者）64岁男性，因“心悸2天”于20137有充血症状有充血症状/体征体征无充血症状无充血症状/体征体征利尿剂利尿剂+ACEI(或或ARB）+受体阻滞剂受体阻滞剂ACEI(或或ARB）+受体阻受体阻滞剂滞剂仍仍NYHA级，级，LVEF 35%加加醛固酮受体拮抗剂醛固酮受体拮抗剂仍仍NYHA级，级，LVEF35%，窦性心，窦性心律且心率律且心率70次次/分分仍为仍为NYHA级，级，LVEF45%加伊伐布雷定加伊伐布雷定加地高辛加地高辛慢性慢性HF-REF(NYHA级）药级）药物治疗流程物治疗流程有充血症状/体征无充血症状/体征利尿剂+ACEI(或ARB）38小结小结u醛固酮受体拮抗剂能改善慢性收缩性心力衰竭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。适用于（左心衰竭）患者的预后。适用于LVEF35%、NYHA级的患者；已使用级的患者；已使用ACEI（或（或ARB）和和受体阻滞剂治疗，仍持续有症状的患者（受体阻滞剂治疗，仍持续有症状的患者（类，类，A级）；级）；AMI后，后，LVEF 40%，有心衰症状或既，有心衰症状或既往有糖尿病史者。往有糖尿病史者。u为避免高钾血症和肾功能损害，为避免高钾血症和肾功能损害，血血钾钾 5 mmol/L,肾功能受损（肾功能受损（Cr 221 mol/L，或，或eGFR 5.5 mmol/L,应应减量或停用；从减量或停用；从小剂小剂量起始量起始，逐渐加量，尤其螺内酯不推荐大剂量。，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