Author + information
- Received March 22, 2019
- Revision received June 21, 2019
- Accepted July 29, 2019
- Published online October 28, 2019.
- Stephen J. Greene, MDa,b,∗ (, )@SJGreene_md@DCRINews,
- Adam D. DeVore, MD, MHSa,b,
- Shubin Sheng, PhDb,
- Gregg C. Fonarow, MDc,
- Javed Butler, MD, MPH, MBAd,
- Robert M. Califf, MDe,f,g,
- Adrian F. Hernandez, MD, MHSa,b,
- Roland A. Matsouaka, PhDb,
- Ayman Samman Tahhan, MDh,
- Kevin L. Thomas, MDa,b,
- Muthiah Vaduganathan, MD, MPHi,
- Clyde W. Yancy, MD, MScj,
- Eric D. Peterson, MD, MPHa,b,
- Christopher M. O’Connor, MDk and
- Robert J. Mentz, MDa,b
- aDuke Clinical Research Institute, Durham, North Carolina
- bDivision of Cardiology, Duke University School of Medicine, Durham, North Carolina
- cAhmanson–UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, California
- dDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- eDuke Forge, Duke University School of Medicine, Durham, North Carolina
- fDepartment of Medicine, Stanford University, Stanford, California
- gVerily Life Sciences (Alphabet), South San Francisco, California
- hEmory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia
- iBrigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts
- jDivision of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- kInova Heart and Vascular Institute, Falls Church, Virginia
- ↵∗Address for correspondence:
Dr. Stephen J. Greene, Duke Clinical Research Institute, 200 Morris Street, Durham, North Carolina 27701.
Objectives This study sought to determine the degree to which U.S. patients enrolled in a heart failure (HF) trial represent patients in routine U.S. clinical practice according to race and sex.
Background Black patients and women are frequently under-represented in HF clinical trials. However, the degree to which black patients and women enrolled in trials represent such patients in routine practice is unclear.
Methods The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized patients hospitalized for HF to receive nesiritide or placebo from May 2007 to August 2010 and was neutral for clinical endpoints. This analysis compared non-Hispanic white (n = 1,494) and black (n = 1,012) patients enrolled in ASCEND-HF from the U.S. versus non-Hispanic white and black patients included in a U.S. hospitalized HF registry (i.e., Get With The Guidelines–Heart Failure [GWTG-HF]) during the ASCEND-HF enrollment period and meeting trial eligibility criteria.
Results Among 79,291 white and black registry patients, 49,063 (62%) met trial eligibility criteria (white, n = 37,883 [77.2%]; black, n = 11,180 [22.8%]). Women represented 35% and 49% of the ASCEND-HF and trial-eligible GWTG-HF cohorts, respectively. Compared with trial-enrolled patients, trial-eligible GWTG-HF patients tended to be older with higher blood pressure and higher ejection fraction. Trial-eligible patients had higher in-hospital mortality (2.3% vs. 1.3%), 30-day readmission (20.2% vs. 16.8%), and 180-day mortality (21.2% vs. 18.6%) than those enrolled in the trial (all p < 0.02), with consistent mortality findings by race and sex. After propensity score matching, mortality rates were similar; however, trial-eligible patients continued to have higher rates of 30-day readmission (23.1% vs. 17.3%; p < 0.01), driven by differences among black patients and women (all p for interaction ≤0.02).
Conclusions Patients with HF seen in U.S. practice and eligible for the ASCEND-HF trial had worse clinical outcomes than those enrolled in the trial. After accounting for clinical characteristics, trial-eligible real-world patients continued to have higher rates of 30-day readmission, driven by differences among black patients and women. Social, behavioral, and other unmeasured factors may impair representativeness of patients enrolled in HF trials, particularly among racial/ethnic minorities and women. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852)
This analysis was funded by an internal grant from the Duke Clinical Research Institute to Dr. Greene. Scios Inc. provided financial and material support for the ASCEND-HF trial. Database management and statistical analysis were performed by the Duke Clinical Research Institute. Dr. Greene is supported by the National Heart, Lung, and Blood Institute T32 post-doctoral training grant (T32HL069749-14), a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; has received research support from Amgen, Bristol-Myers Squibb, and Novartis; and serves on an advisory board for Amgen. Dr. DeVore has received research funding from Akros Medical, the American Heart Association, Amgen, Bayer, Intra-Cellular Therapies, Luitpold Pharmaceuticals, the National Heart, Lung, and Blood Institute, Novartis, and the Patient-Centered Outcomes Research Institute; and serves as a consultant for Novartis. Dr. Fonarow has received research funding from the National Institutes of Health (NIH); and serves as a consultant for Amgen, Bayer, Medtronic, and Novartis. Dr. Butler has received research support from the NIH, the Patient-Centered Outcomes Research Institute, and the European Union; and serves as a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, Stealth Peptides, SC Pharma, Vifor, and ZS Pharma. Dr. Califf was the Commissioner of Food and Drugs for the U.S. Food and Drug Administration from February 2016 to January 2017 and Deputy Commissioner for Medical Products and Tobacco for the U.S. Food and Drug Administration from February 2015 to January 2016; serves on the corporate board for Cytokinetics; is the Board Chair for the People-Centered Research Foundation; has received consulting fees from Merck, Biogen, Genentech, Eli Lilly, and Boehringer Ingelheim; and is employed as a scientific advisor by Verily Life Sciences (Alphabet). Dr. Hernandez has received consulting fees from AstraZeneca, Bayer, Boston Scientific, Merck, Novartis, and Sanofi; and research support from AstraZeneca, GlaxoSmithKline, Luitpold, Merck, and Novartis. Dr. O’Connor has received grant support from the NIH and Roche Diagnostics. Dr. Samman Tahhan is supported by the Abraham J. & Phyllis Katz Foundation and an NIH National Institute on Aging grant (AG051633). 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 has served on advisory boards or received research funding from Amgen, AstraZeneca, Bayer AG, and Baxter Healthcare. Dr. Peterson has received consultant/honoraria from AstraZeneca, Bayer, Janssen, Merck & Co., and Sanofi; and research grants from AstraZeneca, Bayer, Daiichi Sankyo, Genentech, Janssen, Regeneron, Sanofi, Merck & Co., and Amgen Inc. Dr. Mentz has received research support from the NIH (U01HL125511-01A1, U10HL110312, and R01AG045551-01A1), Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, Luitpold, Medtronic, Merck, Novartis, Otsuka, and ResMed; honoraria from Abbott, AstraZeneca, Bayer, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, and ResMed; and has served on an advisory board for Amgen, Luitpold, Merck, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John Teerlink, MD, served as Guest Editor for this paper.
- Received March 22, 2019.
- Revision received June 21, 2019.
- Accepted July 29, 2019.
- 2019 American College of Cardiology Foundation
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