{"doi":"10.1056/nejmoa1409077","title":"Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure","abstract":"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.).","journal":"New England Journal of Medicine","year":2014,"id":11594,"datarank":9.640043025947207,"base_score":8.81818627792769,"endowment":8.81818627792769,"self_citation_contribution":1.3227279416891538,"citation_network_contribution":8.317315084258054,"self_endowment_contribution":1.3227279416891538,"citer_contribution":8.317315084258054,"corpus_percentile":85.9,"corpus_rank":1853,"citation_count":6755,"citer_count":148,"citers_with_citation_signal":148,"citers_with_endowment":148,"datacite_reuse_total":0,"is_dataset":false,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2014-09-11","authors":[{"id":92418,"name":"Milton Packer","orcid":"0000-0003-1828-2387","position":1,"is_corresponding":false},{"id":57261,"name":"Akshay S. Desai","orcid":"0000-0002-1443-0701","position":2,"is_corresponding":false},{"id":92419,"name":"Jianjian Gong","orcid":"0000-0001-7981-0054","position":3,"is_corresponding":false},{"id":92420,"name":"Martin P. Lefkowitz","orcid":null,"position":4,"is_corresponding":false},{"id":92421,"name":"Adel R. Rizkala","orcid":"0000-0002-4118-4489","position":5,"is_corresponding":false},{"id":39753,"name":"Jean L. Rouleau","orcid":"0009-0004-0592-8091","position":6,"is_corresponding":false},{"id":92422,"name":"Victor C. Shi","orcid":null,"position":7,"is_corresponding":false},{"id":27970,"name":"Scott D. Solomon","orcid":"0000-0003-3698-9597","position":8,"is_corresponding":false},{"id":92423,"name":"Karl Swedberg","orcid":"0000-0002-6358-2154","position":9,"is_corresponding":false},{"id":92424,"name":"Michael R. Zile","orcid":"0000-0001-7076-221X","position":10,"is_corresponding":false},{"id":92425,"name":"Martin Lefkowitz","orcid":null,"position":11,"is_corresponding":false},{"id":92426,"name":"Victor Shi","orcid":"0000-0002-2533-4379","position":12,"is_corresponding":false},{"id":2612,"name":"John J.V. McMurray","orcid":"0000-0002-6317-3975","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}