Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or warfarin for venous thromboembolism: a post hoc analysis of the Hokusai-VTE study.

Abstract

To investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE). Post hoc analysis of the Hokusai-VTE study, a multicentre, randomised, double-blind trial comparing edoxaban with warfarin for acute symptomatic VTE. Women below 50 years receiving edoxaban or warfarin for treatment of VTE. We collected data on diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding events. Occurrence of major and clinically relevant nonmajor (CRNM) abnormal vaginal bleeding events. In all, 628 women aged under 50 years were treated with edoxaban and 665 with warfarin. The rate of abnormal vaginal bleeding was 15/100 person-years (py) (95% CI 11-19) in women receiving edoxaban and 9/100 py (95% CI 6-12) in the warfarin group (hazard ratio: 1.7, 95% CI 1.1-2.5). Major abnormal vaginal bleeding occurred in eight (1.3%) women on edoxaban and in three (0.9%) women receiving warfarin [odds ratio (OR) 2.8; 95% CI 0.8-10.8], and CRNM abnormal vaginal bleeding occurred in 53 (8.4%) women treated with edoxaban and in 37 (5.6%) on warfarin therapy (OR 1.6, 95% CI 1.0-2.4). Over 85% of all vaginal bleeds were characterised by heavy menstrual bleeding. Major bleeds frequently required treatment, and in more than 75% of patients anticoagulant therapy was adjusted. The severity of clinical presentation and course of major and CRNM bleeds was mild in most patients. Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin. Reassuringly, most events could be managed conservatively and had a mild outcome. Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.