发布日期：2014 年 9 月
英文标题：
Angiotensin-neprilysin inhibition versus enalapril in heart failure.
作者：
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees.
出处：N Engl J Med. 2014 Sep 11;371(11):993-1004.
内容介绍：PARADIGM-HF 是一项随机双盲的大型 3 期临床试验，平均随访时间长达 27 个月，极有可能对临床实践造成非常深远的影响。该研究共纳入了 8399 名 NYHA 分级为 2-4 级的心衰患者，纳入标准为 LVEF ≤ 35%、血利钠肽水平升高以及至少使用相当于 10 mg/d 的依那普利的 ACEI/ARB 类药物治疗 4 周。这些患者将被随机分配到 LCZ696（200 mg，bid）组和依那普利（10 mg，bid）组。和传统的血管紧张素转化酶抑制剂（ACEI）类药物依那普利相比，使用 LCZ696 的慢性心衰患者因心衰而住院的次数减少了，其心血管死亡率也下降了（LCZ696 组患者的心血管死亡或心衰住院率为 21.8%，而依那普利组为 26.5%。LCZ696 组和依那普利组患者的全因死亡率分别为 13.3% 和 16.5%。）
摘要展示：
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.).
