Female participation in cardiovascular trials showed similar relative treatment effects compared to males, with a pooled difference on the natural log scale of -0.02 (95% CI -0.05 to 0.01; p=0.23).
Meta-Analysis (n=801,000)
Yes
Are there significant sex differences in efficacy outcomes in cardiovascular trials?
Despite underrepresentation in cardiovascular trials, female participation was sufficient to exclude major sex differences in efficacy outcomes.
Effect estimate: Pooled difference on natural log scale -0.02 (95% CI -0.05 to 0.01)
p-value: p=0.23
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 (PPR F ). 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 PPR F was 0.75 (interquartile range: 0.64–0.83), while 58% of trials had a PPR F 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, I 2 = 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.
Bijl et al. (2025) conducted a meta-analysis in Cardiovascular disease (n=801,000). Various cardiovascular treatments vs. Male participants was evaluated on Difference in treatment effect on study-specific primary endpoints between females and males (Pooled difference on natural log scale -0.02, 95% CI -0.05 to 0.01, p=0.23). Female participation in cardiovascular trials showed similar relative treatment effects compared to males, with a pooled difference on the natural log scale of -0.02 (95% CI -0.05 to 0.01; p=0.23).