Influence of sex on long-term prognosis in patients with atrial fibrillation treated with oral anticoagulants. Results from the prospective, nationwide FANTASIIA study

Background: While many risk factors for Atrial Fibrillation (AF) have been identified, there are important differences in their relative impact between sexes. The aim of our study was to investigate the influence of sex as a long-term predictor of adverse events in "real world" AF patients treated with direct oral anticoagulants. Methods: The FANTASIIA registry is a prospective, national and multicentric study including outpatients with anticoagulated AF patients. Baseline characteristics and adverse events at 3 years of follow-up were collected and classified by sex. Cox multivariate analysis was performed to investigate the role of sex in major events and composite outcomes. Results: A total of 1956 patients were included in the study. 43.9% of them were women, with a mean age of 73.8 +/- 9.4 years (women were older 76.5 +/- 7.9 vs 71.7 +/- 10.1, p<0.001). Women had higher rate of cardiovascular risk factors and higher mean of CHA(2)DS(2)-VASc (4.4 +/- 1.4 vs 3.7 +/- 1.6, p<0.001) and HAS-BLED (2.1 +/- 1.0 vs 1.9 +/- 1.1, p<0.001) than men. After 3 years of follow-up, rates of major events were similar in both groups with limit difference for all-cause mortality (4.4%/year in women vs 5.6%/year in men; p = 0.056). However, all the composite events were more frequent in women. We observed in the non-adjusted adverse events lower rate of all-cause mortality (HR 0.62, 95%CI 0.47-0.81; p<0.001), composite 1 outcomes (HR 0.80, 95%CI 0.65-0.98; p = 0.029) and composite 2 (HR 0.77, 95%CI 0.64-0.94; p = 0.010) in women compared with men. In multivariate Cox regression analysis observed that female sex was an independently protector factor for all-cause mortality and for the composite outcomes 1 and 2. Conclusions: In this "real world" study of anticoagulated AF patients, women could have a protective role against development of adverse events, mainly on all-cause mortality and combined events.