Stephen J Greene1, Adam D DeVore2, Shubin Sheng3, Gregg C Fonarow4, Javed Butler5, Robert M Califf6, Adrian F Hernandez2, Roland A Matsouaka3, Ayman Samman Tahhan7, Kevin L Thomas2, Muthiah Vaduganathan8, Clyde W Yancy9, Eric D Peterson2, Christopher M O'Connor10, Robert J Mentz2. 1. Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina. Electronic address: stephen.greene@duke.edu. 2. Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina. 3. Division of Cardiology, Duke University School of Medicine, Durham, North Carolina. 4. Ahmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, California. 5. Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. 6. Duke Forge, Duke University School of Medicine, Durham, North Carolina; Department of Medicine, Stanford University, Stanford, California; Verily Life Sciences (Alphabet), South San Francisco, California. 7. Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia. 8. Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts. 9. Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Inova Heart and Vascular Institute, Falls Church, Virginia.
Abstract
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).
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).
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