Gender and contemporary risk of adverse events in atrial fibrillation

Background and Aims The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial. Methods The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005–2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities. Results 78 852 patients were included with AF, aged 40–75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5–70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87–0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83–0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83–0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94–1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96–1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97–1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA₂DS₂-VA (ignoring gender) superior to CHA₂DS₂-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45). Conclusions Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.