Sex disparities in enrollment and reporting of outcomes by sex in contemporary clinical trials of atrial fibrillation.

BACKGROUND: Underrepresentation of females in randomized controlled trials (RCTs) limits generalizability and quality of the evidence guiding treatment of females. This study aimed to measure the sex disparities in participants' recruitment in RCTs of atrial fibrillation (AF) and determine associated factors, and to describe the frequency of outcomes reported by sex. METHODS: MEDLINE was searched to identify RCTs of AF published between January 1, 2011, and November 20, 2021, in 12 top-tier journals. We measured the enrollment of females using the enrollment disparity difference (EDD) which is the difference between the proportion of females in the trial and the proportion of females with AF in the underlying general population (obtained from the Global Burden of Disease). Random-effects meta-analyses of the EDD were performed, and multivariable meta-regression was used to explore factors associated with disparity estimates. We also determined the proportion of trials that included sex-stratified results. RESULTS: Out of 1133 records screened, 142 trials were included, reporting on a total of 133 532 participants. The random-effects summary EDD was -0.125 (95% confidence interval [CI] = -0.143 to -0.108), indicating that females were under-enrolled by 12.5 percentage points. Female enrollment was higher in trials with higher sample size (<250 vs. >750, adjusted odds ratio [aOR] 1.065, 95% CI: 1.008-1.125), higher mean participants' age (aOR: 1.006, 95% CI: 1.002-1.009), and lower in trials conducted in North America compared to Europe (aOR: 0.945, 95% CI: 0.898-0.995). Only 36 trials (25.4%) reported outcomes by sex, and of these 29 (80.6%) performed statistical testing of the sex-by-treatment interaction. CONCLUSION: Females remain substantially less represented in RCTs of AF, and sex-stratified reporting of primary outcomes is infrequent. These findings call for urgent action to improve sex equity in enrollment and sex-stratified outcomes' reporting in RCTs of AF.