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

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).

Keywords: enrollment; heart failure; race; sex; trial.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Selection of the Analytic Cohorts and Outline of Study Group Comparisons

This study included 3 comparisons: Part 1, trial-ineligible versus trial-eligible patients; Part 2, trial-eligible versus patients enrolled in the trial (unadjusted); and Part 3, trial-eligible versus patients enrolled in the trial (propensity score matched). ACS = acute coronary syndrome; ASCEND-HF = Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure; BNP = B-type natriuretic peptide; CMS = Centers for Medicare & Medicaid Services; GWTG-HF = Get With The Guidelines–Heart Failure; HF = heart failure; NT-proBNP = N-terminal pro–B-type natriuretic peptide.

FIGURE 2. In-Hospital and Post-Discharge Outcomes According to Trial Eligibility and Enrollment Status

(A) Event rates for trial-ineligible, trial-eligible, and trial-enrolled patients. (B) Event rates for trial-eligible and trial-enrolled patients after propensity score matching. Abbreviations as in Figure 1.

FIGURE 3. Outcomes According To Trial Eligibility And Enrollment Status Stratified According To Race And Sex

The Figure displays event rates for (A) trial-ineligible versus trial-eligible patients, (B) trial-eligible versus trial-enrolled patients without adjustment, and (C) trial-eligible versus trial-enrolled patients after propensity score matching. Abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. Trial- and Patient-Level Representativeness of the ASCEND-HF Trial According to Race and Sex

ASCEND-HF = Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure; HF = heart failure.