慢性心力衰竭用药选择-上海瑞金医院施仲伟课件

1、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)01102111278983638845982553796Months47737426483459930481024421118311217260.10.20.30.40.50.60.70.8安慰剂（66/126）依那普利（46/127）Cumulative Probability of Death死亡率40%（p=0.002）CONSENSUS Trial S

2、tudy Group. N Engl J Med 1987; 316:14291435上海瑞金医院施仲伟SOLVD Treatment Trial：MortalityN Engl J Med 1991, 325:293-30216% Risk Reductionp = 0.0036010203040500612182430364248MonthsMortality (%)PlaceboEnalapril2 568 symptomatic class IIIII patientsAll-Cause MortalityYearsProbability of Event00.050.10.150.2

3、0.250.301230.350.44ACE-I2995 2250 1617 892 223Placebo2971 2184 1521 853 138Flather MD, et al. Lancet 2000; 355(9215):15751581OR: 0.74 (0.660.83, p0.0001)To avoid 1 death, 15 pts would have to be treated for 30 monthsACE-I: 702/2995 (23.4%)Placebo: 866/2971 (29.1%)TRACEEchocardiographicEF 35%AIREClin

4、ical and/or radiographic signs of HFSAVERadionuclideEF 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)0.00091年724 (11.3%)828 (13.0%)0.85 (0.76-0.94)0.00282年1038 (16.2%)1248 (19.6%)0.79 (0.72-0.86)0.00014年1419 (22.2%)1659 (26

5、.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ACEIELITE 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%

6、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，安全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=0.16P=0.08P=0.21上海瑞金医院施仲伟治疗心力衰竭：ARB间接比较ACEI

7、CHARM-Alternative TrialMedian follow-up of 33.7 monthsCandesartann=1013Placebon=1015Completed Studyn=1011Completed Studyn=1014Lost to follow-upn=2Lost to follow-upn=12028 patients randomisedNYHA IIIV, LVEF 40%ACE inhibitor intolerant上海瑞金医院施仲伟CHARM-Alternative: Primary outcome CV death or CHF hospita

8、lisationNumber at riskCandesartan 1013 929 831 434 122Placebo 1015 887 798 427 1260123years01020304050PlaceboCandesartan%HR 0.77 (95% CI 0.670.89), p=0.0004Adjusted HR 0.70, p0.00013.5406 (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=0.11SOL

9、VD-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 IIIV906例死亡（记录事件）缬沙坦40 mg bid， 上调至160 mg bid安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)

10、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 TrialMedian follow-up of 41 monthsCandesartann=1276Placebon=1272Completed Studyn=1273Completed Studyn=1271Lost to follow-upn=3Lost to follow-upn=12548 patients randomisedNYHA IIIV, LVEF 40%ACE inhibitor treated上海瑞金医院施仲伟CHARM-Adde

11、d: Primary outcomeCV death or CHF hospitalisationNumber at riskCandesartan1276 1176 1063 948 457Placebo1272 1136 1013 906 4220123years01020304050PlaceboCandesartan3.5HR 0.85 (95% CI 0.750.96), p=0.011Adjusted HR 0.85, p=0.010483 (37.9%)538 (42.3%)%上海瑞金医院施仲伟Captopril00.050.10.150.20.250.3061218243036

12、Probability of EventVALIANT: Mortality by TreatmentN Engl J Med 2003; 349:1893-1905Valsartan4909 4464 4272 4007 2648 1437 357MonthsValsartan vs. Captopril: HR = 1.00; P = 0.982Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726Captopril4909 4428 4241 4018 2635 1432 364Valsartan + Cap4885 4414 4265 3994 2648 1435 382ValsartanValsartan + Captopril上海瑞金医院施仲伟ONTARGET: Kaplan-Meier Curves for the Primary Outcome in the Three GroupsThe ONTARGET Investigators. NEJM 2008, 358(15):1547-1559Telmisartan vs Ramipril: RR=1.01 (0.941.09)Combination vs Ramipril: RR=