Sex differences in venous thromboembolism outcomes: findings from the GARFIELD-VTE registry

Background: The association of sex with clinical outcome risk in venous thromboembolism (VTE) is unclear. Objective: To investigate sex differences in clinical outcomes and anticoagulation effectiveness in VTE in the GARFIELD-VTE registry. Methods: Outcomes included all-cause mortality, VTE recurrence, major and any bleeding, myocardial infarction (MI)/acute coronary syndrome (ACS), and stroke/transient ischaemic attack (TIA) over 3 years of follow-up. Hazard ratios were calculated using Cox proportional hazard models with an assessment of sex interactions with parenteral, vitamin K antagonist (VKA), and direct oral anticoagulant (DOAC) therapies. Results: Of 10,650 patients, 5290 (49.7%) were female and 5360 were male. Females and males had comparable ages (median [Q1-Q3]; females: 60.6 [44.0–72.9] years, males: 60.0 [48.0–70.3] years), body mass index (females: 27.6 [23.6–32.7] kg/m2, males: 27.1 [24.4–30.6] kg/m2), and anticoagulant treatment. Females had greater risk of major (adjusted hazard ratio [95% CI (1.25 [1.01–1.55]) and any bleeding (1.32 [1.18–1.47]) than males, but lower risk of recurrent VTE (0.82 [0.72; 0.94]), MI/ACS (0.52 [0.36–0.76]) and stroke/TIA (0.72 [0.52–0.99]). VKA-treated females had greater risk of major (1.69 [1.16–2.48]) and any bleeding (1.43 [1.18–1.73]) than VKA-treated males, while DOAC-treated females had greater risk of any bleeding (1.37 [1.17–1.61]) but not major bleeding (1.22 [0.86–1.72]) than DOAC-treated males. Sensitivity analyses excluding patients with active cancer (N = 9752) yielded similar results. Conclusions: Compared with males, females with VTE have a greater risk of bleeding, but a lower risk of recurrent VTE, MI/ACS, and stroke/TIA. Sex appears to affect the relationship between VKA and DOAC treatment and bleeding in VTE.