Author + information
- Received October 3, 2019
- Revision received December 6, 2019
- Accepted December 19, 2019
- Published online March 11, 2020.
- Nasrien E. Ibrahim, MDa,b,
- John C. Burnett Jr., MDc,
- Javed Butler, MD, MPH, MBAd,
- Alexander Camacho, PhDa,
- G. Michael Felker, MDe,
- Mona Fiuzat, PharmDe,
- Christopher O’Connor, MDe,f,
- Scott D. Solomon, MDb,g,
- Muthiah Vaduganathan, MD, MPHb,g,
- Michael R. Zile, MDh and
- James L. Januzzi Jr., MDa,b,i,∗ (, )@JJHeart_doc
- aCardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- bHarvard Medical School, Boston, Massachusetts
- cCardiology Division, Mayo Clinic, Rochester, Minnesota
- dCardiology Division, University of Mississippi, Jackson, Mississippi
- eCardiology Division, Duke University, Durham, North Carolina
- fInova Heart and Vascular Institute, Fairfax, Virginia
- gBrigham and Women’s Hospital, Boston, Massachusetts
- hMedical University of South Carolina, Charleston, South Carolina, and Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina
- iBaim Institute for Clinical Research, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. James L. Januzzi, Jr, Massachusetts General Hospital, 32 Fruit Street, Yawkey 5984, Boston, Massachusetts 02114.
• BNP and NT-proBNP are used as inclusion criteria in several HF clinical trials.
• Despite widespread use, there is inconsistency in how BNP and NT-proBNP are utilized.
• We call for standardization of natriuretic peptide inclusion criteria across HF trials.
This study investigated the use of natriuretic peptides as inclusion criteria and to develop recommendations regarding their use. B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) are commonly used as inclusion criteria for heart failure (HF) clinical trials, but no consensus exists regarding their optimal use for this purpose. A comprehensive search of the Aggregate Analysis of ClincalTrials.gov database identified 3,446 HF trials. Of these, 365 recently completed or ongoing HF clinical trials (10.6%) used either BNP or NT-proBNP as inclusion criteria. A panel of experts discussed current practices and a path forward for the use of natriuretic peptides as inclusion criteria for HF trials. Significant variations existed across trials regarding which natriuretic peptide and which cutoff value were used. Overall, 43% used both natriuretic peptides, 33% used only NT-proBNP, and 24% used only BNP in determining eligibility. Studies using BNP and NT-proBNP concentrations as inclusion criteria had higher cardiovascular event rates and higher concentrations for study entry and were generally associated with higher event rates. Areas of uncertainty included use in certain patient populations in which natriuretic peptides are historically lower (e.g., black patients, obese patients, patients with HF with preserved ejection fraction) or higher (older patients, patients with atrial fibrillation). This paper discusses best practices regarding use of BNP or NT-proBNP in clinical trials and identification of gaps in medical literature, including importance of documentation in ClinicalTrials.gov studies to inform future research efforts.
Dr. Ibrahim is supported by the Dennis and Marilyn Barry Research Fund in Cardiology (Boston, Massachusetts). Dr. Januzzi is supported by the Hutter Family Professorship (Boston, Massachusetts). Dr. Ibrahim has received honorarium from Roche Diagnostics. Dr. Burnett is a consultant for Novartis. Dr. Felker has received research support from U.S. National Institutes of Health (NIH)/ National Heart, Lung, and Blood Institute (NHLBI), 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, Rocket Pharma, and SC Pharma. Dr. O’Connor has received support from NIH/NHLBI, U.S. Food and Drug Administration, Merck, Bayer, Abbott, and Medtronic; and is a consultant for Merck, Bayer, and Bristol-Myers Squibb. Dr. Fiuzat has received research funding from Roche Diagnostics. Dr. O’Connor has received research funding from Roche Diagnostics; and is a consultant for Merck, Bayer, Bristol-Myers Squibb, Windtree, and Arena Pharmaceuticals. 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, NIH/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, GlaxoSmith Kline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/National Center for Advancing Translational Sciences award UL 1TR002541); and serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, and Boehringer Ingelheim. Dr. Zile has received research support from NHLBI, Department of Defense, and Veterans’ Administration; and is a consultant for Abbott, Boston Scientific, CVRx, EBR Systems, Endotronics, Edwards Lifesciences, Ironwood, Merck, Medtronic, Myokardia, Novartis, AND V Wave. Dr. Januzzi is a trustee of the American College of Cardiology and a board member of Imbria Pharmaceuticals; and has received support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex, and Prevencio; is a consultant for Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and serves on clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer-Ingelheim, Janssen, and Takeda. 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.
- Received October 3, 2019.
- Revision received December 6, 2019.
- Accepted December 19, 2019.
- 2020 American College of Cardiology Foundation
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