Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation: Should We Use a CHA₂DS₂-VA Score Rather Than CHA₂DS₂-VASc?

BACKGROUND: Stroke risk in atrial fbrillation is assessed by using the CHA ₂DS ₂-VASc score. Sex category (Sc, ie, female sex) confers 1 point on CHA ₂DS ₂-VASc. We hypothesized that female sex is a stroke risk modifer, rather than an overall risk factor, when added to a CHA ₂DS ₂-VA (sexindependent thromboembolism risk) score scale. METHODS: Using 3 nationwide registries, we identifed patients with incident nonvalvular atrial fbrillation from January 1, 1997, through December 31, 2015. Patients receiving oral anticoagulant treatment at baseline were excluded, and person-time was censored at the time of treatment initiation (if any). CHA ₂DS ₂-VA scores were calculated for men and women, and were followed for up to 1 year in the Danish National Patient Registry. The primary outcome was a primary hospital code for ischemic stroke or systemic embolism (thromboembolism). We calculated crude event rates for risk strata as events per 100 person-years. For quantifying absolute risk of stroke, we calculated risks based on the pseudovalue method. Female sex as a prognostic factor was investigated by inclusion as an interaction term on the CHA ₂DS ₂-VA score to calculate the thromboembolic risk ratio for different score points. RESULTS: A total of 239671 patients with atrial fbrillation (48.7% women) contributed to the analyses. The mean ages for women and men were 76.6 years and 70.3 years, respectively; the mean CHA ₂DS ₂-VA scores were 2.7 for women and 2.3 for men. The overall 1-year thromboembolic rate per 100 person-years for women was 7.3 and 5.7 for men. The 1-year absolute risk of thromboembolism was 0.5% among men and women with a CHA ₂DS ₂-VA score of 0 and increased up to >7% among very comorbid patients (score >5). The risk ratio (male as reference) across points >t1 indicated that women exhibit a higher stroke risk. The interaction was statistically signifcant (P<0.001). CONCLUSIONS: Female sex is a risk modifer for stroke in patients with atrial fbrillation. Initial decisions on oral anticoagulant treatment could be guided by a CHA ₂DS ₂-VA score (ie, excluding the sex category criterion), but the Sc risk component modifes and accentuates stroke risk in women who would have been eligible for oral anticoagulant treatment on the basis of =2 additional stroke risk factors.