COMPARATIVE STUDY
JOURNAL ARTICLE
MULTICENTER STUDY
RANDOMIZED CONTROLLED TRIAL

Angiotensin-neprilysin inhibition versus enalapril in heart failure

John J V McMurray, Milton Packer, Akshay S Desai, Jianjian Gong, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau, Victor C Shi, Scott D Solomon, Karl Swedberg, Michael R Zile
New England Journal of Medicine 2014 September 11, 371 (11): 993-1004
25176015

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.).

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Amandeep Chadha

why not 20 mg BID of Enalapril??

1

Amila Heendeniya Vidanaral

Really well done RCT!
Only issues I had was the Enalapril dosing at 10mg BID (would a higher dose change the outcome? - would be interesting to see how a higher dose would change the outcome and/or harm)

0

Daniel Schwartz

A methodologically robust study which reduced hard clinical endpoints. A welcome addition to the heart failure literature which should change clinical practice.

0

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