Abstract 18005: Underrepresentation of Women in Clinical Trials of Heart Failure With Reduced Ejection Fraction

Abstract

Background: There are established sex-specific differences in heart failure with reduced ejection fraction (HFrEF) outcomes. Randomized clinical trials (RCTs) based on cardiovascular outcome benefits, typically either reduced cardiovascular mortality or hospitalization for heart failure (HHF), and influence current guidelines for therapy. Objectives: To evaluate the representation of women in HFrEF RCTs that observed reduced all-cause or cardiovascular mortality or HHF. Methods: We queried Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, and PubMed for HFrEF RCTs that reported a statistically significant benefit of intervention resulting in improved mortality or HHF published from 1980 to 2021. We estimated representation using the participation-to-prevalence ratio (PPR). PPR was calculated based on the proportion of women with HFrEF in the Framingham cohort (40%). A PPR of 0.8 to 1.2 was considered representative. Results: The final analysis included 33 RCTs. All trials except two were mentioned in the 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America Guidelines for the Management of Heart Failure. Women represented 23.2% of enrolled participants (n = 24,363/ 104,972), ranging from 11.4% to 40.1% per-trial. Overall PPR was 0.58, with per-trial estimates ranging from 0.29 - 1.00. Five trials (15.2%) had a PPR of women representative of the disease population. Representation didn’t change significantly by the decade examined. The proportion of women in North American and Multiregional trials was significantly greater than in trials conducted in Europe (p = 0.04). The proportion of women was greater in industry trials compared to government-funded trials (p = 0.05). Conclusions: Women are underrepresented in HFrEF RCTs that have demonstrated mortality or HHF benefits, which may affect the sex-specific generalizability of major trial results. Sustained efforts are warranted to ensure equitable and appropriate inclusion of women in HFrEF trials.