Representation of women in heart failure trials: does it matter?

Sex differences across the HF spectrum are well defined and pertain to risk factors, aetiology, provision of evidence-based therapies, referral to services, treatment response and clinical outcomes in both the acute and chronic HF syndrome setting.1 Much of our evidence base for the management of HF is derived from randomised clinical trials (RCTs) that inform best practice for the treatment of HF and shape guideline recommendations. A recent analysis of 740 cardiovascular trials (102 trials in HF) registered between 2010 and 2017 has shown the lowest PPR of 0.48 in HF trials.5 This is despite the fact that legislature such as the National Institutes of Health Revitalization Act stipulates the inclusion of women and men in clinical trials proportionate to the sex-related prevalence of the disease under investigation, to provide data on the treatment effect of interventions/treatments studied in both women and men. Underenrolment in clinical trials deprive women with HF of the benefits of trial participation, including receipt of contemporary evidence-based therapy, receipt of better-quality medical care with closer clinical follow-up and better outcomes than those of eligible non-participants.1 Furthermore, interventions that been shown to be beneficial in clinical trials that recruited mainly male participants have been shown in subsequent observational studies to have unexpected adverse effects in women11 with the current study reporting sex differences in outcomes for select RCTs included in the descriptive analysis (online supplemental table 5). Trial characteristics associated with under-enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review.