Neth Heart J. 2025 Nov 12. doi: 10.1007/s12471-025-01999-4. Online ahead of print.
ABSTRACT
BACKGROUND: Prior studies showed underrepresentation of females in cardiovascular disease (CVD) clinical trials, potentially hindering accurate treatment effect estimates. We assessed the female contribution to treatment effect estimates in selected CVD trials and explored sex differences in efficacy outcomes.
METHODS: We analyzed completed (1997-2024) randomized controlled CVD trials performed via the Dutch WCN Investigator Network. Female participation was quantified using the Participation to Prevalence (in the population) Ratio (PPRF). In trials with a cardiovascular event as the primary efficacy endpoint, a meta-analysis was conducted to evaluate differences in treatment effect on the study-specific primary endpoint between females and males using a random-effects model.
RESULTS: In 115 trials investigating various treatments across different cardiovascular domains (801 k participants, 29.1% females), the median PPRF was 0.75 (interquartile range: 0.64-0.83), while 58% of trials had a PPRF below 0.8 (underrepresentation). Based on 46 trials, female contribution to primary endpoints was lower than their sample size contribution (mean 26.2% versus 28.5%). Similarly, based on 66 trials, female contribution to sex-stratified efficacy estimates was lower than their sample size contribution (27.4% versus 29.2%). Regarding the primary endpoint, the relative treatment effect was similar in females and males: pooled difference of the relative effect measure on the natural log scale of -0.02, 95% CI -0.05 to 0.01, p = 0.23, I2 = 11%.
CONCLUSION: Despite underrepresentation, female participation in the selected WCN-CVD trials was sufficient to exclude major sex differences in efficacy. Given the limited and heterogeneous trial sample, further disease-specific studies are needed, and greater female inclusion remains essential for equity and safety insights.
PMID:41222889 | DOI:10.1007/s12471-025-01999-4