Taking cardiology clinical trials to the next level: A call to action

Abstract

Physicians previously perceived heart disease to be a man's disease; yet, since 1984, more women have died of ischemic heart disease. Because women who develop obstructive coronary heart disease and heart failure tend to do so 10 years later than men, cardiology clinical trials that use arbitrary age cutoffs or exclusion criteria based on comorbidities and polypharmacy often limit the pool of potential participants to a greater extent for women. Issues related to trial design and insufficient accounting for female-predominant disease patterns have contributed to low rates of enrollment of women in certain domains of cardiology research. Accordingly, women do not benefit from as rich an evidence base for cardiology as men. Here, we review major sex differences in heart disease and discuss areas of cardiology research in which women have been underrepresented. Considering the widespread sex differences in cardiovascular structure and function, it is important to include balanced numbers of women and men in cardiovascular clinical trials. Beyond inclusion, sex-specific reporting is also essential. Moreover, with ongoing developments of clinical-trial methodology, it is imperative to seek innovative ways to learn as much as possible about how interventions behave in women and men. Adaptive trials are specifically identified as promising opportunities to consider sex-based analyses at interim stages, allowing sex-specific flexibility as these trials unfold. Finally, we emphasize the importance of factoring sex as a biological variable into the design, analysis, and reporting of preclinical research, because this research critically informs the design and execution of clinical trials.