Citation: JACC Heart Failure. 2020 Jun 10.Journal: JACC. Heart failure.Published: ; 2020ISSN: 2213-1779.Full author list: Mann DL; Greene SJ; Givertz MM; Vader JM; Starling RC; Ambrosy AP; Shah P; McNulty SE; Mahr C; Gupta D; Redfield MM; Lala A; Lewis GD; Mohammed SF; Gilotra NA; DeVore AD; Gorodeski EZ; Desvigne-Nickens P; Hernandez AF; Braunwald E; LIFE Investigators.UI/PMID: 32641226.Subject(s): IN PROCESS -- NOT YET INDEXEDInstitution(s): MedStar Heart & Vascular InstituteActivity type: Journal Article.Medline article type(s): Journal Article | ReviewOnline resources: Click here to access onlineDigital Object Identifier: https://dx.doi.org/10.1016/j.jchf.2020.05.005 (Click here)Abbreviated citation: JACC Heart Fail. 2020 Jun 10.Abstract: The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients >=18 years of age with advanced HF, defined as an EF <=35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] >=250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] >=800 pg/ml), and >=1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736). Copyright (c) 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.