Countering sex and gender bias in cardiovascular research requires more than equal recruitment and sex disaggregated analyses

The US Multiple Risk Factor Intervention Trial in the 1970s screened 325 348 men and no women for risk of cardiovascular disease; 12 866 of these men were identified as high risk and offered prevention strategies.1 Dozens of publications resulted, producing a robust evidence base on cardiovascular risk and prevention—in white men.1 Tellingly, the trial’s acronym was “Mr Fit.”

This flagrant sex and ethnic bias was part of a wider pattern. The Physicians Health Study, which established the efficacy of aspirin for prevention of myocardial infarction,2 and various cardiovascular prevention studies that ran till the mid-1990s were limited to white men.34 Indeed, in the second half of the 20th century, women in childbearing years were routinely excluded from medical research trials on the grounds that their hormone cycles made study populations too heterogeneous,5 and to avoid a repeat of the thalidomide tragedy in which an experimental drug proved teratogenic.6 Yet cardiovascular disease, then as now, is the leading cause of death in women globally.7

Multiple initiatives have helped to achieve sex balanced recruitment to trials. The US National Institutes of Health mandated the inclusion of women and people from ethnic minorities in government funded health research from 1994,56 and in the UK the National Institute for Health and Care Research published guidance on representativeness of sex and gender in 2020.4 Despite these measures and overall increased awareness, representation of women in cardiovascular trials remains significantly lower than that of men.789 A cross specialty review of 20 000 trials showed that under-representation of women is worse in cardiovascular …