慢性心力衰竭用药选择-上海瑞金医院施仲伟

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,*,慢性心力衰竭用药选择,ACEIs,vs,ARBs,上海瑞金医院施仲伟,ACE抑制剂治疗心力衰竭疗效确凿,Consensus trial：总死亡率比较,死亡率31%p=0.001,Placebo (N=126),Enalapril (N=127),0,1,102,111,2,78,98,3,63,88,4,59,82,5,53,79,6,Months,47,73,7,42,64,8,34,59,9,30,48,10,24,42,11,18,31,12,17,26,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,安慰剂,（,66/126）,依那普利,（46/127,）,Cumulative Probability of Death,死亡率,40%（p=0.002）,CONSENSUS Trial Study Group.N Engl J Med 1987;316:14291435,上海瑞金医院施仲伟,SOLVD Treatment Trial：Mortality,N Engl J Med 1991,325:293-302,16%Risk Reduction,p=0.0036,0,10,20,30,40,50,0,6,12,18,24,30,36,42,48,Months,Mortality(%),Placebo,Enalapril,2 568 symptomatic class IIIII patients,All-Cause Mortality,Years,Probability of Event,0,0.05,0.1,0.15,0.2,0.25,0.3,0,1,2,3,0.35,0.4,4,ACE-I2995 2250 1617 892 223,Placebo2971 2184 1521 853 138,Flather MD,et al.Lancet 2000;355(9215):15751581,OR:0.74(0.660.83,p0.0001),To avoid 1 death,15 pts would have to be treated for 30 months,ACE-I:702/2995(23.4%),Placebo:866/2971(29.1%),TRACE,EchocardiographicEF,35%,AIRE,Clinical and/or radiographic signs of HF,SAVE,RadionuclideEF,40%,上海瑞金医院施仲伟,ACEI治疗慢性心力衰竭/左室功能异常,前瞻性五大临床试验死亡率资料总结,ACEI组,(n=6391),对照组,(n=6372),RR(95%CI),P 值,6周,212(3.3%),281(4.4%),0.73(0.61-0.88),0.0009,1年,724(11.3%),828(13.0%),0.85(0.76-0.94),0.0028,2年,1038(16.2%),1248(19.6%),0.79(0.72-0.86),0.0001,4年,1419(22.2%),1659(26.0%),0.80(0.74-0.87),0.0001,总计,1467(23.0%),1710(26.8%),0.80(0.74-0.87),0.0001,上海瑞金医院施仲伟,上海瑞金医院施仲伟,治疗心力衰竭：ARB直接挑战ACEI,心力衰竭领域三项直接比较的随机试验,ELITE：假设氯沙坦肾脏平安性优于卡托普利,ELITE-2：假设氯沙坦降低死亡率优于卡托普利,OPTIMAAL：假定氯沙坦降低死亡率优于卡托普利,上海瑞金医院施仲伟,氯沙坦老年患者评价研究ELITE,多中心前瞻性随机双盲平行临床试验观察48周,722例65岁有病症心力衰竭NYHA IIIV，EF40%,氯沙坦组n=352：12.5 mg 25 mg 50 mg qd,卡托普利组n=370：6.25 mg 50 mg tid,主要终点：持续肾功能异常发生率*,氯沙坦组和卡托普利组均为10.5%p=0.63,上海瑞金医院施仲伟,Pitt B,et al.Lancet 1997,349:747-752,*治疗期间血清肌酐较基线值增高,0.3 mg/dl，514天后复查证实,ELITE 试验：结果,氯沙坦组,卡托普利组,P 值,肾功能异常发生率,37（10.5%）,39（10.5%）,0.63,死亡/心力衰竭住院率,33（9.4%）,49（13.2%）,0.075,总死亡率（降低46%）,17（4.8%）,32（8.7%）,0.035,心力衰竭住院率,20（5.7%）,21（5.7%）,0.89,心脏猝死率,5(1.4%),14(3.8%),60岁，NYHA IIIV，LVEF40%,标准治疗利尿剂/地高辛，-阻滞剂25%,卡托普利 50mg tid,n=1574,氯沙坦 50mg qd,n=1578,主要终点：总死亡率,二级终点：心脏猝死,其他终点：总死亡率/住院率，平安性耐受性,累计观察死亡,510,例,上海瑞金医院施仲伟,ELITE-II 试验：研究终点小结,Pitt B,et al.Lancet 2000;355:1582-7,上海瑞金医院施仲伟,总死亡率,心脏猝死,总死亡/住院,15.9%17.7%,7.3%9.0%,44.9%47.7%,卡托普利组（,n=1574,）,氯沙坦组（,n=1578,）,P=0.16,P=0.08,P=0.21,心肌梗死后使用ARB氯沙坦的最正确试验OPTIMAAL,第一项在急性心肌梗死后患者中直接比较ACEI 和ARB治疗对死亡率影响的大规模临床试验,5477例50岁急性心肌梗死后的高危患者,卡托普利组n=2733，50mg tid,氯沙坦组 n=2744，50mg qd,平均随访2.7年,Dickstein K,et al.Lancet 2002,360(9335):752-760,上海瑞金医院施仲伟,25 20 15 10 5 0,0 6 12 18 24 30 36,Losartan,Captopril,Relative risk 1.13,(95%CI 0.991.28),p=0.069,Number at risk,Losartan 2744 2504 2432 2390 2344 2301 1285,Captopril 2733 2534 2463 2423 2374 2329 1309,months,All-cause mortality(%),OPTIMAAL:总死亡率比较Kaplan-Meier曲线,既生瑜，何生亮：ACEI 三气 ARB,试验,比较,主要假设,结果,ELITE,氯沙坦:卡托普利,肾功能异常更少,10.5%:10.5%,ELITE-II,氯沙坦:卡托普利,死亡率更低,17.7%:15.9%,OPTIMAAL,氯沙坦:卡托普利,死亡率更低,18.2%:16.4%,上海瑞金医院施仲伟,上海瑞金医院施仲伟,治疗心力衰竭：ARB间接比较ACEI,CHARM-Alternative Trial,Median follow-up of 33.7 months,Candesartan,n=1013,Placebo,n=1015,Completed Study,n=1011,Completed Study,n=1014,Lost to follow-up,n=2,Lost to follow-up,n=1,2028 patients randomised,NYHA IIIV,LVEF,40%,ACE inhibitor intolerant,上海瑞金医院施仲伟,CHARM-Alternative:Primary outcome,CV,death,or CHF hospitalisation,Number at risk,Candesartan 1013 929 831 434 122,Placebo 1015 887 798 427 126,0,1,2,3,years,0,10,20,30,40,50,Placebo,Candesartan,%,HR 0.77(95%CI 0.670.89),p=0.0004Adjusted HR 0.70,p0.0001,3.5,406(40.0%),334(33.0%),上海瑞金医院施仲伟,ACEI与ARB治疗心力衰竭：间接比较,试验,治疗药物,*,死亡/心衰住院,总死亡率,CHARM(n=2028),坎地沙坦,-,23%,p=0.0004,-,13%,p=0.11,SOLVD-P(n=2568),依那普利,-,26%,p0.0001,-,16%,p=0.0036,汇总分析(n=7105),ACE抑制剂,-,35%,p0.001,-,23%,p18岁;EF40%;NYHA IIIV,906例死亡记录事件,缬沙坦,40 mg bid，,上调至,160,mg bid,抚慰剂,随机分组,接受常规治疗包括ACEI、利尿剂、地高辛、-阻滞剂分层随机,Val-HeFT 试验设计,上海瑞金医院施仲伟,Val-HeFT：主要终点分析,终点,事件数,危险比,（95%CI）,P 值,缬沙坦组,（n=2511）,安慰剂组,（n=2499）,所有原因死亡,495,(19.7%),484,(19.4%),1.02,(0.901.15),0.800,死亡,/,病残率,723,(28.8%),801,(32.1%),0.87,(0.790.96),0.009,上海瑞金医院施仲伟,CHARM-Added Trial,Median follow-up of 41 months,Candesartan,n=1276,Placebo,n=1272,Completed Study,n=1273,Completed Study,n=1271,Lost to follow-up,n=3,Lost to follow-up,n=1,2548 patients randomised,NYHA IIIV,LVEF,40%,ACE inhibitor treated,上海瑞金医院施仲伟,CHARM-Added:,Primary outcome,CV,death,or CHF hospitalisation,Number at risk,Candesartan1276 1176 1063 948 457,Placebo1272 1136 1013 906 422,0,1,2,3,years,0,10,20,30,40,50,Placebo,Candesartan,3.5,HR 0.85 (95%CI 0.750.96),p=0.011Adjusted HR 0.85,p=0.010,483(37.9%),538(42.3%),%,上海瑞金医院施仲伟,Captopril,0,0.05,0.1,0.15,0.2,0.25,0.3,0,6,12,18,24,30,36,Probability of Event,VALIANT:Mortality by Treatment,N Engl J Med,2003;349:1893-1905,Valsartan4909 4464 4272 4007 2648 1437 357,Months,Valsartan vs.Captopril:HR=1.00;P=0.982,Valsartan+Captopril vs.Captopril:HR=0.98;P=0.726,Captopril4909 4428 4241 4018 2635 1432 364,Valsartan+Cap4885 4414 4265 3994 2648 1435 382,Valsartan,Valsartan+Captopril,上海瑞金医院施仲伟,ONTARGET:Kaplan-Meier Curves for the Primary Outc