Sex related differences in patients with acute venous thromboembolism treated with new oral anticoagulants. A meta-analysis of the interventional trials

BACKGROUND: Gender differences have been reported in patients with acute VTE treated with antithrombotic drugs. OBJECTIVE: To address the relationship between gender and new oral anticoagulants (NOACs), we performed a meta-analysis to evaluate the incidence of recurrent VTE and major plus clinically relevant non-major bleedings in males and females, with acute VTE, treated with NOACs over the treatment period. DESIGN: Systematic review and meta-analysis of double blind randomized controlled trials (RCTs). DATA SOURCES: MEDLINE, Cochrane Library of Clinical Trials (up to September 2015). STUDY SELECTION: RCTs that compared the beneficial and harmful effects of NOAC drugs (apixaban, dabigatran, edoxaban and rivaroxaban). DATA EXTRACTION: Three authors abstracted data. Study-specific risk ratios (RR) were combined using random-effects model. RESULTS: Nine studies including 16,372 patients were selected. No significant difference for the incidence of recurrent VTE was found between men and women. Compared to men, women had a higher incidence of major bleedings plus clinically relevant minor bleedings (5.3% and 7.9% respectively; RR: 0.635; 95% CI: 0.54-0.74; p<0.001). The subgroup analysis showed a significant gender difference in incidence of major bleedings and clinically relevant minor bleedings only for Edoxaban (RR: 0.52; 95% CI: 0.42-0.64; p<0.001). CONCLUSIONS: This meta-analysis showed, compared to men, a higher risk of bleeding in women with acute VTE treated with NOACs. Future trials should evaluate the effect of gender on bleeding in patients with acute VTE treated with NOACs.