Underrepresentation of Women in Reduced Ejection Heart Failure Clinical Trials With Improved Mortality or Hospitalization

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), influence current guidelines for therapy. OBJECTIVES: The authors evaluate the representation of women in HFrEF RCTs that observed reduced all-cause or cardiovascular mortality or HHF. METHODS: We queried Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, 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). A PPR of 0.8 to 1.2 was considered representative. CONCLUSIONS: Women are underrepresented in HFrEF RCTs that have demonstrated mortality or HHF benefits and influence current guidelines. Representation is key to further delineation of sex-specific differences in major trial results. Sustained efforts are warranted to ensure equitable and appropriate inclusion of women in HFrEF trials.