血管紧张素-脑啡肽酶抑制剂与依那普利治疗心力衰竭的比较。
Angiotensin-neprilysin inhibition versus enalapril in heart failure.
机构信息
From the British Heart Foundation (BHF) Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M.); the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston (A.S.D., S.D.S.); Novartis Pharmaceuticals, East Hanover, NJ (J.G., M.P.L., A.R.R., V.C.S.); Institut de Cardiologie de Montréal, Université de Montréal, Montreal (J.L.R.); the Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); National Heart and Lung Institute, Imperial College London, London (K.S.); and the Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston (M.R.Z.).
出版信息
N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
BACKGROUND
We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.
METHODS
In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.
RESULTS
The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.
CONCLUSIONS
LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).
背景
我们比较了血管紧张素受体-脑啡肽酶抑制剂 LCZ696 与依那普利在射血分数降低的心力衰竭患者中的疗效。此前的研究表明，依那普利可改善此类患者的生存率。
方法
在这项双盲试验中，我们将 8442 例射血分数为 40%或更低的 II 级、III 级或 IV 级心力衰竭患者随机分为 LCZ696 组（每日 2 次，每次 200mg）或依那普利组（每日 2 次，每次 10mg），两组均接受推荐的治疗。主要终点为心血管原因死亡或心力衰竭住院的复合终点，但试验设计旨在检测 LCZ696 组心血管原因死亡率的差异。
结果
根据预先设定的规则，中位随访 27 个月后提前终止了试验，因为 LCZ696 的获益优势明显。研究结束时，LCZ696 组有 914 例（21.8%）患者和依那普利组有 1117 例（26.5%）患者发生主要终点事件（LCZ696 组的风险比为 0.80；95%置信区间[CI]为 0.73 至 0.87；P<0.001）。LCZ696 组共有 711 例（17.0%）患者和依那普利组共有 835 例（19.8%）患者死亡（任何原因死亡的风险比为 0.84；95%CI 为 0.76 至 0.93；P<0.001）；其中，558 例（13.3%）和 693 例（16.5%）患者死于心血管原因（风险比为 0.80；95%CI 为 0.71 至 0.89；P<0.001）。与依那普利相比，LCZ696 还使心力衰竭住院风险降低 21%（P<0.001），并减轻心力衰竭的症状和身体限制（P=0.001）。LCZ696 组低血压和非严重血管性水肿的发生率较高，但肾功能损害、高钾血症和咳嗽的发生率较低。
结论
LCZ696 降低死亡和心力衰竭住院风险的疗效优于依那普利。（由诺华资助；PARADIGM-HF ClinicalTrials.gov 编号，NCT01035255）。
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