Author + information
- Received February 15, 2015
- Accepted March 8, 2015
- Published online April 28, 2015.
- Jacob P. Kelly, MD∗∗ (, )
- Robert J. Mentz, MD∗,
- Alexandre Mebazaa, MD†,
- Adriaan A. Voors, MD‡,
- Javed Butler, MD, MPH§,
- Lothar Roessig, MD‖,
- Mona Fiuzat, PharmD∗,
- Faiez Zannad, MD¶,
- Bertram Pitt, MD#,
- Christopher M. O’Connor, MD∗ and
- Carolyn S.P. Lam, MBBS∗∗
- ∗Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
- †Department of Anesthesia and Critical Care, University Paris Diderot, Sorbonne Paris Cité, Paris, France
- ‡Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
- §Cardiology Division, Stony Brook University, Stony Brook, New York
- ‖Global Clinical Development, Bayer Pharma AG, Berlin, Germany
- ¶INSERM, Centre d'Investigations Cliniques, Université de Lorraine and CHU de Nancy, Nancy, France
- #University of Michigan School of Medicine, Ann Arbor, Michigan
- ∗∗Department of Cardiology, National Heart Centre Singapore, Singapore
- ↵∗Reprint requests and correspondence:
Dr. Jacob Kelly, Duke University Medical Center, Department of Medicine, 2400 Pratt Street, Durham, North Carolina 27705.
Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the effect of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France, on December 6, 2013.
Dr. Kelly has received funding from a National Institutes of Health Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (5 T32 HL 7101-39). Dr. Mentz has received research support from Gilead Sciences, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Otsuka, Amgen, ResMed, HeartWare, and Luitpold; and has received honoraria from Thoratec. Dr. Mebazza has received speakers honoraria from Cardiorentis, Vifor, Edwards, Orion, and Bayer; and is a consultant for Adrenomed and Cardiorentis. Dr. Voors has received consultancy fees and/or research grants from Alere, AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Cardio3Biosciences, Celladon, Johnson & Johnson, Merck/Merck Sharp & Dohme, Novartis, Servier, Torrent, Trevena, and Vifor. Dr. Butler has served as a consultant to Amgen, BG Medicine, Celladon, Gambro, Janssen, Ono Pharma, Relypsa, Trevena, Takada, Bayer HealthCare, Medtronic, CardioCell, Novartis, Z Pharma, and GE Healthcare; and has received research support from the National Institutes of Health, European Union, and the Health Resources and Services Administration. Dr. Roessig is an employee of Bayer Pharma AG. Dr. Zannad has received grant funding from Novartis, BG Medicine, and Roche Diagnostics, served on a board for Boston Scientific, and served as a consultant for Novartis, Takeda, AstraZeneca, Boehringer Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer, Johnson & Johnson, and ResMed. Dr. Pitt has received consultancy fees and/or stock options from Pfizer Inc., AstraZeneca, Bayer HealthCare, Lilly, Stealth Peptides, SC Pharmaceuticals, Sarfez Pharmaceuticals, and Relypsa. Dr. O’Connor has received research support from Johnson & Johnson and ResMed. Dr. Fiuzat has received research support from ResMed. Dr. Lam has received research support from Boston Scientific, Medtronic, Vifor Pharma, and the National Medical Research Council of Singapore; and is a consultant for Bayer, Novartis Takeda, Merck, AstraZeneca, and DC Devices. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 15, 2015.
- Accepted March 8, 2015.
- 2015 American College of Cardiology Foundation