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.

OBJECTIVE: To investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE). DESIGN AND SETTING: Post hoc analysis of the Hokusai-VTE study, a multicentre, randomised, double-blind trial comparing edoxaban with warfarin for acute symptomatic VTE. POPULATION: Women below 50 years receiving edoxaban or warfarin for treatment of VTE. METHODS: We collected data on diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding events. MAIN OUTCOME MEASURES: Occurrence of major and clinically relevant nonmajor (CRNM) abnormal vaginal bleeding events. RESULTS: 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. CONCLUSIONS: 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. TWEETABLE ABSTRACT: Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.

Direct factor Xa inhibitor edoxaban: from bench to clinical practice.

Edoxaban is a direct factor Xa inhibitor and has become the fourth direct oral anticoagulant (DOAC) approved for stroke prevention in atrial fibrillation (AF) and for treatment and secondary prevention of venous thromboembolism (VTE). This review provides an overview of the key characteristics of edoxaban and clinical evaluation program leading to regulatory approval. Approval for AF and VTE treatment was based on large phase III randomized controlled trials that showed that edoxaban reduces the risk of bleeding compared with warfarin and provides similar protection against thromboembolism. Edoxaban is the second once-daily DOAC, is tested in a reduced dose for patients with a moderate renal impairment, body weight of ≤60 kg or concomitant use of p-glycoprotein inhibitors and thereby is a valuable addition to the therapeutic arsenal of modern anticoagulation. For AF regulatory approval in the USA is limited to patients with a creatinine clearance of 15-95 ml/min. Another limitation is the need for initial parenteral anticoagulation with heparin in treatment of acute VTE.