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.