Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure

作者：McMurray, John J. V.; Packer, Milton^*; Desai, Akshay S.; Gong, Jianjian; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.

来源：New England Journal of Medicine, 2014, 371(11): 993-1004.

DOI：10.1056/NEJMoa1409077

• NEUTRAL ENDOPEPTIDASE INHIBITION
• CONVERTING ENZYME-INHIBITION
• NATRIURETIC-PEPTIDE
• RANDOMIZED-TRIAL
• EJECTION FRACTION
• DOUBLE-BLIND
• MORTALITY
• SURVIVAL
• RECEPTOR
• MORBIDITY

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.

• 出版日期2014-9-11