Representativeness of a Heart Failure Trial by Race and Sex Results From ASCEND-HF and GWTG-HF

• Type of Material: Article
• Authors: Stephen J. Greene, Duke Clinical Research Institute; Adam D. DeVore, Duke Clinical Research Institute; Shubin Sheng, Duke University; Gregg C. Fonarow, University of California Los Angeles; Javed Butler, Emory University; Robert M. Califf, Duke University; Adrian F. Hernandez, Duke Clinical Research Institute; Roland A. Matsouaka, Duke University; Ayman Samman Tahhan, Emory University; Kevin L. Thomas, Duke Clinical Research Institute; Muthiah Vaduganathan, Brigham & Womens Hospital; Clyde W. Yancy, Northwestern University; Eric D. Peterson, Duke Clinical Research Institute; Christopher M. O'Connor, Inova Heart & Vascular Institute; Robert J. Mentz, Duke Clinical Research Institute
• Language: English
• Date: 2019-11-01
• Publisher: Elsevier Science Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by the American College of Cardiology Foundation. Published by Elsevier.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jchf.2019.07.011
• Title of Journal or Parent Work: JACC: Heart Failure
• Volume: 7
• Issue: 11
• Start Page: 980
• End Page: 992
• Grant/Funding Information: Dr. DeVore reports receiving 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 serving as a consultant for Novartis.; 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. Fonarow reports research funding from the National Institutes of Health (NIH); and serving as a consultant for Amgen, Bayer, Medtronic, and Novartis.; Database management and statistical analysis were performed by the Duke Clinical Research Institute.; 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.; 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 (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial.
• Keywords: Women; sex; Cardiovascular System & Cardiology; Participation; Registry; Life Sciences & Biomedicine; race; trial; Minorities; Barriers; heart failure; Cardiac & Cardiovascular Systems; Outcomes; enrollment; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology; Health Sciences, Public Health

Abstract

OBJECTIVES This study sought to determine the degree to which US patients enrolled in a heart failure (HF) trial represent patients in routine US 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 United States versus non-Hispanic white and black patients included in a US 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 according to 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 US 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. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure [ASCEND-HF]; NCT00475852).