Dabigatran Is Associated with a Significantly Lower Risk of Abnormal Uterine Bleeding Than Warfarin in Female Patients of Childbearing Age with Venous Thromboembolism

Introduction: While Direct Oral Anticoagulants (DOACs) have been shown to have an overall equal efficacy as and better safety profile than warfarin in patients with acute venous thromboembolism (VTE), Xa-inhibitors have been associated with a higher risk of abnormal uterine bleeding (AUB). No data regarding AUB with the direct thrombin inhibitor dabigatran etexilate (dabigatran) have been reported to date.

Aim: To determine the risk of AUB during anticoagulation with dabigatran compared to warfarin in female VTE patients aged 18-50 years.

Methods: We performed a post hoc analysis of the pooled RE-COVER studies, two double-blind randomized trials evaluating dabigatran administered at a dose of 150mg twice daily versus warfarin after an initial treatment with parenteral anticoagulants, and the RE-MEDY trial, a double-blind randomized trial that studied the extended use of dabigatran at the same dose versus warfarin, all in patients with VTE. We compared the incidence of AUB, based on a defined preferred terms search in adverse events, in female patients aged 18-50 years who were treated with dabigatran versus who were treated with warfarin. Patients who rolled-over from RE-COVER into RE-MEDY and stayed on the same treatment were accounted for as "only one patient" taking the whole treatment period into consideration, whereas patients who switched treatment were analyzed as two different study subjects.

Results: Of the 2964 women included in the above mentioned trials, 1280 women were in the relevant age category and included in the current analysis. A total of 643 patients were randomized to treatment with dabigatran and 637 to treatment with warfarin. The overall rate of AUB was 5.9% for the women treated with dabigatran and 9.6% in those treated with warfarin, for an Odds Ratio of 0.59 (95% confidence interval 0.39-0.90).

Conclusion: In female VTE patients of 18-50 years old, dabigatran was associated with a significantly 41% lower risk of AUB than warfarin.