Background: The polypill is an emerging strategy for the prevention and management of cardiovascular disease. We assessed the participation of females in randomised controlled trials evaluating polypills for prevention of cardiovascular disease and subsequent sex-specific analyses and reporting.
Methods: Cardiovascular polypill trials were identified through a systematic review. Data were extracted on the use of sex-specific eligibility criteria, female participation, and the conduct, findings, and interpretation of sex-specific analyses.
Results: Of 26 trials included, 12 (46%) excluded groups of females, mainly if pregnant or lactating or of childbearing potential. Female participation ranged from 10% to 73% across trials. Overall, 42% of included participants were female. Of 18 trials conducted in a mostly primary prevention population, females represented 49% of trial participants. In mixed or exclusively secondary prevention trials (n=8), females represented 26% of trial participants. Females represented 46% of trial participants in trials that excluded groups of females (n=12). In trials without explicit exclusion criteria (n=13), females represented 32% of trial participants. Nine out of 26 trials reported sex-stratified analyses (35% of trials; 70% of all participants). Of these, two found some evidence for possible sex differences, both reporting larger blood pressure effects in females than males. Four trials provided sex considerations in the discussion section of the report.
Conclusion: The participation of females in cardiovascular polypill trials is substantially higher in primary prevention trials as compared to trials conducted in mixed or exclusively secondary prevention populations. The use of sex-specific eligibility criteria was not linked to lower female participation. Sex-specific reporting is sparsely conducted, although most frequent in larger trials.
Historically, women have been underrepresented in clinical trials, making it difficult to determine if treatments work differently in males and females. Despite efforts to include more females, their participation in cardiovascular research remains lower than expected. This study investigated the participation of females in clinical trials that evaluate the effectiveness of polypills. Polypills, which combine multiple medications into a single pill, are a promising approach for managing cardiovascular diseases. We conducted a systematic review of 26 trials to assess how many females were included, whether there were sex-specific eligibility criteria, and if the trials analysed and reported results separately for males and females. We found that nearly half of the trials (46%) excluded certain groups of females, often due to pregnancy or the potential to become pregnant. The participation of females in these trials varied 10% to 73%, with an overall average of 42%. Females were better represented in trials in individuals with a history of cardiovascular disease (49% participation) than in those treating existing conditions (26% participation). The explicit exclusion of specific female groups did not result in lower overall female participation. Only 35% of the trials reported results separately for males and females, and just two of these found differences between sexes, specifically in blood pressure outcomes. The study concludes that while females are reasonably well-represented in some polypill trials, there is still a lack of consistent sex-specific analysis and reporting, which is crucial for understanding how treatments may affect males and females differently.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.