Reference : Angiotensin-neprilysin inhibition versus enalapril in heart failure.
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Angiotensin-neprilysin inhibition versus enalapril in heart failure.
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. [> >]
Neyses, Ludwig mailto [University of Luxembourg > Rectorate > Research Service]
The New England journal of medicine
Yes (verified by ORBilu)
United States
[en] Aged ; Aminobutyrates/adverse effects/therapeutic use ; Angiotensin Receptor Antagonists/adverse effects/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/adverse effects/therapeutic use ; Double-Blind Method ; Drug Combinations ; Enalapril/adverse effects/therapeutic use ; Female ; Heart Failure/drug therapy/mortality ; Hospitalization/statistics & numerical data ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neprilysin/antagonists & inhibitors ; Stroke Volume ; Tetrazoles/adverse effects/therapeutic use
[en] 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 number, NCT01035255.).

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