Abstract Body (Do not enter title and authors here):
Background: Despite increasing recognition of sex differences in the burden of cardiovascular (CV) diseases, women have historically been underrepresented in clinical trials.

Aims: The study aimed to systematically quantify the extent of sex disparity in the enrollment of CV trials and explore the annual enrollment trends of women in CV trials.

Methods: The analysis included studies that: (1) were registered in ClinicalTrials.gov up to February 2024; (2) were randomized trials involving ≥1 intervention; (3) investigated ≥1 CV condition, as determined by Medical Subject Heading descriptors. The exclusion criteria were: (1) studies without available enrollment information; (2) studies exclusively enrolling men or women; and (3) studies with ≤100 participants. We computed enrollment disparity difference (EDD), defined as the difference between the proportion of women in trial participants and the proportion of women with CV diseases in the general population, based on the Global Burden of Disease estimates matched by country/geographic region and enrollment period. Random-effects meta-analysis was performed to summarize the overall enrollment disparity. Subgroup analysis by trial characteristics was conducted. Meta-regression was used to assess the association of enrollment disparity with the start year of the trials.

Results: A total of 1,687 CV trials were identified from 484,781 studies. Among 2,198,317 trial participants for whom sex was reported, 819,570 (37.3%) were women. EDD in CV trials was -0.105 (95% CI, -0.113 to -0.097), indicating that women were under-enrolled by 10.5% (Figure 1). Except for valvular heart disease trials, disparities were evident across other CV disease trials, with the most remarkable under-enrollment of women in peripheral artery disease trials (-0.302 [95% CI, -0.324 to -0.279]). Disparities were more prominent in trials with larger sample sizes, longer study durations, device or procedural interventions, and data monitoring committee oversight (p<0.001 for subgroup differences; Figure 2). There was a significant yet modest improvement in the representation of women over time (increase of 0.0028 [95% CI, 0.0011 to 0.0045] in EDD per start year of trials; p=0.001; Figure 3).

Conclusion: Women remain substantially underrepresented in CV trials, particularly in peripheral artery disease trials. The findings underscore the imperative for interventions to mitigate sex inequity in the enrollment of CV trials.