Endpoints in Heart Failure Drug Development: History and Future

Mona Fiuzat; Naomi Lowy; Norman Stockbridge; Marco Sbolli; Federica Latta; Jo Ann Lindenfeld; Eldrin F. Lewis; William T. Abraham; John Teerlink; Mary Walsh; Paul Heidenreich; Biykem Bozkurt; Randall C. Starling; Scott Solomon; G. Michael Felker; Javed Butler; Clyde Yancy; Lynne W. Stevenson; Christopher O'Connor; Ellis Unger; Robert Temple; John McMurray

doi:10.1016/j.jchf.2019.12.011

Endpoints in Heart Failure Drug Development: History and Future

Mona Fiuzat^*, Naomi Lowy, Norman Stockbridge, Marco Sbolli, Federica Latta, Jo Ann Lindenfeld, Eldrin F. Lewis, William T. Abraham, John Teerlink, Mary Walsh, Paul Heidenreich, Biykem Bozkurt, Randall C. Starling, Scott Solomon, G. Michael Felker, Javed Butler, Clyde Yancy, Lynne W. Stevenson, Christopher O'Connor, Ellis UngerRobert Temple, John McMurray

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Review article › peer-review

38 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	429-440
Number of pages	12
Journal	JACC: Heart Failure
Volume	8
Issue number	6
DOIs	https://doi.org/10.1016/j.jchf.2019.12.011
State	Published - Jun 2020

Funding

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. 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.

Keywords

FDA
clinical trials
endpoints
heart failure
patient-reported outcomes

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jchf.2019.12.011

Cite this

Fiuzat, M., Lowy, N., Stockbridge, N., Sbolli, M., Latta, F., Lindenfeld, J. A., Lewis, E. F., Abraham, W. T., Teerlink, J., Walsh, M., Heidenreich, P., Bozkurt, B., Starling, R. C., Solomon, S., Felker, G. M., Butler, J., Yancy, C., Stevenson, L. W., O'Connor, C., ... McMurray, J. (2020). Endpoints in Heart Failure Drug Development: History and Future. JACC: Heart Failure, 8(6), 429-440. https://doi.org/10.1016/j.jchf.2019.12.011

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title = "Endpoints in Heart Failure Drug Development: History and Future",

abstract = "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.",

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year = "2020",

month = jun,

doi = "10.1016/j.jchf.2019.12.011",

language = "English (US)",

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Fiuzat, M, Lowy, N, Stockbridge, N, Sbolli, M, Latta, F, Lindenfeld, JA, Lewis, EF, Abraham, WT, Teerlink, J, Walsh, M, Heidenreich, P, Bozkurt, B, Starling, RC, Solomon, S, Felker, GM, Butler, J, Yancy, C, Stevenson, LW, O'Connor, C, Unger, E, Temple, R & McMurray, J 2020, 'Endpoints in Heart Failure Drug Development: History and Future', JACC: Heart Failure, vol. 8, no. 6, pp. 429-440. https://doi.org/10.1016/j.jchf.2019.12.011

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AU - Fiuzat, Mona

AU - Lowy, Naomi

AU - Stockbridge, Norman

AU - Sbolli, Marco

AU - Latta, Federica

AU - Lindenfeld, Jo Ann

AU - Lewis, Eldrin F.

AU - Abraham, William T.

AU - Teerlink, John

AU - Walsh, Mary

AU - Heidenreich, Paul

AU - Bozkurt, Biykem

AU - Starling, Randall C.

AU - Solomon, Scott

AU - Felker, G. Michael

AU - Butler, Javed

AU - Yancy, Clyde

AU - Stevenson, Lynne W.

AU - O'Connor, Christopher

AU - Unger, Ellis

AU - Temple, Robert

AU - McMurray, John

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Endpoints in Heart Failure Drug Development: History and Future

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