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.).