PMID- 32641226 OWN - NLM STAT- MEDLINE DCOM- 20201009 LR - 20240320 IS - 2213-1787 (Electronic) IS - 2213-1779 (Print) IS - 2213-1779 (Linking) VI - 8 IP - 10 DP - 2020 Oct TI - Sacubitril/Valsartan in Advanced Heart Failure With Reduced Ejection Fraction: Rationale and Design of the LIFE Trial. PG - 789-799 LID - S2213-1779(20)30272-9 [pii] LID - 10.1016/j.jchf.2020.05.005 [doi] AB - 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 /=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). CI - Copyright (c) 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Mann, Douglas L AU - Mann DL AD - Department of Medicine, Washington University, St. Louis, Missouri. Electronic address: dmann@wustl.edu. FAU - Greene, Stephen J AU - Greene SJ AD - Department of Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina. FAU - Givertz, Michael M AU - Givertz MM AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Vader, Justin M AU - Vader JM AD - Department of Medicine, Washington University, St. Louis, Missouri. FAU - Starling, Randall C AU - Starling RC AD - Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio. FAU - Ambrosy, Andrew P AU - Ambrosy AP AD - Division of Research, Kaiser Permanente Northern California, Oakland, California. FAU - Shah, Palak AU - Shah P AD - Inova Heart and Vascular Institute, Falls Church, Virginia. FAU - McNulty, Steven E AU - McNulty SE AD - Duke Clinical Research Institute, Duke University, Durham, North Carolina. FAU - Mahr, Claudius AU - Mahr C AD - Department of Medicine, University of Washington, Seattle, Washington. FAU - Gupta, Divya AU - Gupta D AD - Department of Medicine, Emory University, Atlanta, Georgia. FAU - Redfield, Margaret M AU - Redfield MM AD - Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. FAU - Lala, Anuradha AU - Lala A AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Lewis, Gregory D AU - Lewis GD AD - Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. FAU - Mohammed, Selma F AU - Mohammed SF AD - MedStar Washington Hospital Center, Washington, DC. FAU - Gilotra, Nisha A AU - Gilotra NA AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - DeVore, Adam D AU - DeVore AD AD - Department of Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina. FAU - Gorodeski, Eiran Z AU - Gorodeski EZ AD - Department of Medicine, Harrington Heart and Vascular Center, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Desvigne-Nickens, Patrice AU - Desvigne-Nickens P AD - Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Baltimore, Maryland. FAU - Hernandez, Adrian F AU - Hernandez AF AD - Department of Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina. FAU - Braunwald, Eugene AU - Braunwald E AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. CN - LIFE Investigators LA - eng SI - ClinicalTrials.gov/NCT02816736 GR - U10 HL110337/HL/NHLBI NIH HHS/United States GR - U10 HL110342/HL/NHLBI NIH HHS/United States PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200610 PL - United States TA - JACC Heart Fail JT - JACC. Heart failure JID - 101598241 RN - 0 (Aminobutyrates) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Biphenyl Compounds) RN - 0 (Cardiotonic Agents) RN - 0 (Drug Combinations) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination) RN - 0 (Tetrazoles) RN - 80M03YXJ7I (Valsartan) SB - IM CIN - JACC Heart Fail. 2020 Nov;8(11):959-960. PMID: 33121709 EIN - JACC Heart Fail. 2020 Dec;8(12):1059. PMID: 33272389 MH - Humans MH - *Aminobutyrates/therapeutic use MH - *Angiotensin Receptor Antagonists/therapeutic use MH - Betacoronavirus MH - Biphenyl Compounds MH - Cardiotonic Agents/therapeutic use MH - Coronavirus Infections MH - COVID-19 MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Combinations MH - Early Termination of Clinical Trials MH - Glomerular Filtration Rate MH - *Heart Failure/drug therapy/metabolism/physiopathology MH - Heart Transplantation MH - Heart-Assist Devices MH - Hospitalization/statistics & numerical data MH - Hypotension/chemically induced MH - Natriuretic Peptide, Brain/metabolism MH - Pandemics MH - Peptide Fragments/metabolism MH - Pneumonia, Viral MH - SARS-CoV-2 MH - Stroke Volume MH - *Tetrazoles/therapeutic use MH - Valsartan MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic PMC - PMC7286640 OTO - NOTNLM OT - NYHA functional class IV OT - heart failure OT - sacubitril/valsartan OT - valsartan EDAT- 2020/07/10 06:00 MHDA- 2020/10/10 06:00 PMCR- 2020/06/10 CRDT- 2020/07/10 06:00 PHST- 2020/04/21 00:00 [received] PHST- 2020/05/18 00:00 [revised] PHST- 2020/05/19 00:00 [accepted] PHST- 2020/07/10 06:00 [pubmed] PHST- 2020/10/10 06:00 [medline] PHST- 2020/07/10 06:00 [entrez] PHST- 2020/06/10 00:00 [pmc-release] AID - S2213-1779(20)30272-9 [pii] AID - 10.1016/j.jchf.2020.05.005 [doi] PST - ppublish SO - JACC Heart Fail. 2020 Oct;8(10):789-799. doi: 10.1016/j.jchf.2020.05.005. Epub 2020 Jun 10.