Author + information
- Received September 25, 2019
- Revision received December 12, 2019
- Accepted December 19, 2019
- Published online May 25, 2020.
- Mona Fiuzat, PharmDa,b,∗ (, )
- Naomi Lowy, MDb,
- Norman Stockbridge, MD, PhDb,
- Marco Sbolli, MDc,
- Federica Latta, MDc,
- JoAnn Lindenfeld, MDd,
- Eldrin F. Lewis, MD, MPHe,
- William T. Abraham, MDf,
- John Teerlink, MDg,
- Mary Walsh, MDh,
- Paul Heidenreich, MDi,
- Biykem Bozkurt, MDj,
- Randall C. Starling, MD, MPHk,
- Scott Solomon, MDe,
- G. Michael Felker, MDa,
- Javed Butler, MDl,
- Clyde Yancy, MDm,
- Lynne W. Stevenson, MDd,
- Christopher O'Connor, MDc,
- Ellis Unger, MDb,
- Robert Temple, MDb and
- John McMurray, MDn
- aDuke University and Duke Clinical Research Institute, Durham, North Carolina
- bU.S. Food and Drug Administration, Silver Spring, Maryland
- cInova Heart and Vascular Institute, Falls Church, Virginia
- dHeart Failure and Transplantation Section, Vanderbilt University, Nashville, Tennessee
- eCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts
- fDepartment of Medicine, Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio
- gDivision of Cardiology, San Francisco VA Medical Center, and University of California San Francisco, San Francisco, California
- hSt. Vincent Heart Center, Indianapolis, Indiana
- iVA Palo Alto Health Care System, Palo Alto, California
- jWinters Center for Heart Failure, DeBakey VA Medical Center, Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas
- kDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
- lDepartment of Medicine, University of Mississippi, Jackson, Mississippi
- mDivision of Cardiology, Northwestern University, Chicago, Illinois
- nBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
- ↵∗Address for correspondence:
Dr. Mona Fiuzat, Duke University Medical Center, Box 3850, Durham North Carolina 27710.
• HF patients experience a high burden of symptoms and functional limitations.
• There remains an unmet need for new HF drugs, despite successful therapies that improve morbidity and mortality.
• The majority of HF drugs in the United States are approved for reducing hospitalization and mortality, with only a few having an indication for improving quality of life, physical function, or symptoms.
• Improvements in symptoms, physical function, or quality of life are potentially approvable endpoints in drug development.
• Drug development should include a focus on symptomatic and functional benefit in HF patients, in addition to drugs that improve survival or reduce hospitalization.
Heart failure (HF) patients experience a high burden of symptoms and functional limitations, and morbidity and mortality remain high despite successful therapies. The majority of HF drugs in the United States are approved for reducing hospitalization and mortality, while only a few have indications for improving quality of life, physical function, or symptoms. Patient-reported outcomes that directly measure patient’s perception of health status (symptoms, physical function, or quality of life) are potentially approvable endpoints in drug development. This paper summarizes the history of endpoints used for HF drug approvals in the United States and reviews endpoints that measure symptoms, physical function, or quality of life in HF patients.
Drs. Lowy and Stockbridge are employees of the U.S. Food and Drug Administration. Dr. Latta is an employee of Inova. Dr. Lindenfeld has received consulting and/or research support from Abbott, AstraZeneca, Edwards Lifesciences, Boehringer Ingelheim, V-wave, Vifor, CVRx, and Impulse DYnamics. Dr. Abraham is a consultant for Abbott, ARCA biopharma, Boehringer Ingelheim, CVRx, Edwards Lifesciences, Sensible Medical; a compensated principal investigator for studies conducted by various companies; and is a member of the board of Cardionomic. Dr. Teerlink has received research support from and is a consultant for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cytokinetics, EBR Systems, Medtronic, Merck, Novartis, scPharma, and Windtree Therapeutics. Dr. Bozkurt serves as a member of the Clinical Event Committee, Abbott Vascular, Respicardia Registry Steering Committee; and has received consulting and/or research support from Anthem; and is a consultant for scPharmaceuticals. Dr. Solomon has received research support from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, U.S. National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI), Novartis, Sanofi, Pasteur, Theracos; and is a consultant for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. Dr. Felker has received research support from NHLBI (NIH grant U-10HL110312), American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; and is a consultant for Novartis, Amgen, Bristol-Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and SC Pharma. Dr. Butler has received consulting and/or research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, Janssen, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Sanofi, and Vifor. Dr. Lewis is a consultant for and has received research support from Novartis, Amgen, Merck, and Dal-Cor. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the FDA or the US Department of Health and Human Services. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Barry Greenberg, MD, served as Guest Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received September 25, 2019.
- Revision received December 12, 2019.
- Accepted December 19, 2019.
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