Author + information
- Douglas L. Mann, MD1,∗,
- Stephen J. Greene, MD2,3,
- Michael M. Givertz, MD4,
- Justin M. Vader, MD1,
- Randall C. Starling, MD MPH5,
- Andrew P. Ambrosy, MD6,
- Palak Shah, MD, MS7,
- Steven E. McNulty, MS3,
- Claudius Mahr, DO8,
- Divya Gupta, MD9,
- Margaret M. Redfield, MD10,
- Anuradha Lala, MD11,
- Gregory D. Lewis, MD12,
- Selma F. Mohammed, MD13,
- Nisha A. Gilotra, MD14,
- Adam D. DeVore, MD, MHS2,3,
- Eiran Z. Gorodeski, MD, MPH15,
- Patrice Desvigne-Nickens, MD16,
- Adrian F. Hernandez, MD2,3,
- Eugene Braunwald, MD4,
- for the LIFE Investigators
- 1Department of Medicine, Washington University, St Louis, Missouri
- 2Department of Medicine, Duke University, Durham, North Carolina
- 3Duke Clinical Research Institute, Duke University, Durham, North Carolina
- 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- 5Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
- 6Division of Research, Kaiser Permanente Northern California, Oakland, CA
- 7Inova Heart and Vascular Institute, Falls Church, Virginia
- 8Department of Medicine, University of Washington, Seattle, Washington
- 9Department of Medicine, Emory University, Atlanta, Georgia
- 10Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- 11Icahn School of Medicine at Mount Sinai, New York, New York
- 12Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- 13MedStar Washington Hospital Center, Washington, DC
- 14Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- 15Harrington Heart and Vascular Center, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio
- 16Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Baltimore, Maryland
- ↵∗Corresponding Author: Douglas L. Mann, MD Center for Cardiovascular Research Campus Box 8086, 660 S. Euclid Ave. St. Louis, MO 63110
• There is limited experience with the use of sacubitril/valsartan (S/V) in patients with advanced HF and NYHA class IV symptoms.
• The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial is a 24-week prospective, multicenter, double-blinded, double-dummy, active-comparator trial to assess the safety, efficacy and tolerability of S/ compared with valsartan patients with advanced HFrEF
• The overall study protocol and timeline are depicted in the Central Illustration
• Enrollment in the LIFE trial was halted prematurely because of the COVID-19 pandemic
• The COVID-19 mitigation strategies employed by the LIFE investigators are described
The PARADIGM-HF 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 PARADIGM-HF had NYHA class IV symptomology; accordingly, data that informs the use of S/V among patients with advanced HF are limited. The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) study is a 24-week prospective, multicenter, double-blinded, double-dummy, active-comparator trial to assess the safety, efficacy and tolerability of S/V compared with V in patients with advanced HFrEF. The trial planned to randomize 400 patients age ≥18 years with advanced HF, defined as an EF ≤35%, NYHA 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(s) of advanced HF. Following a 3-7 day open-label run-in period with S/V 24/26 mg twice daily, patients are randomized 1:1 to S/V titrated to 97/103 mg twice daily versus 160 mg V twice daily. The primary endpoint is the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints include clinical outcomes, as well as 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 will consist of the first 335 randomized patients, whose clinical follow-up was not severely impacted by COVID-19.
Disclaimer: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; The National Institute of Arthritis and Infectious Diseases; the National Institutes of Health; or the U.S. Department of Health and Human Services.
- Received April 21, 2020.
- Revision received May 18, 2020.
- Accepted May 19, 2020.
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