Does dabigatran use in women with acute venous thromboembolism reduce the risk of uterine bleeding compared to warfarin?

Analyzed Studies and Patient Population

The post-hoc analysis included 1,280 female patients aged 18–50 years from the randomized double-blind RE-COVER and RE-MEDY studies. They were indicated for anticoagulation therapy for acute venous thromboembolism or prevention of its recurrence. They were randomized into two groups: 643 patients took dabigatran 150 mg twice daily, and the remaining 637 were treated with warfarin (a vitamin K antagonist) with dosage titrated to a target INR of 2.0–3.0. The therapy lasted for 6 months (RE-COVER study) and up to 36 months in the RE-MEDY study. The rates of major and clinically relevant non-major bleeding, as well as abnormal uterine bleeding, treatment management upon occurrence, and the impact of oral contraceptive use on bleeding and deep vein thrombosis recurrence were monitored.

Results

Major bleeding occurred in 3 (0.5%) and 5 (0.8%) patients on dabigatran and warfarin respectively (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.15–2.72). Major or clinically relevant non-major bleeding was reported in 30 (4.7%) patients on dabigatran and 57 (8.9%) patients on warfarin (HR 0.53; 95% CI 0.34–0.83). No bleeding event was fatal.

At the last INR measurement before a bleeding event, 49% of warfarin patients had values within the target range of 2–3, 27% had values < 2, and 24% had values > 3.

Abnormal uterine bleeding was reported in 38 (5.9%) patients treated with dabigatran compared to 61 (9.6%) treated with warfarin (odds ratio [OR] 0.59; 95% CI 0.39–0.90; p = 0.015; HR 0.62; 95% CI 0.41–0.93). In the dabigatran group, the bleeding occurred on average after 110 days, compared to 78 days in the warfarin group. Menorrhagia accounted for 69% and 90% of bleeding events in patients treated with dabigatran and warfarin respectively, and metrorrhagia accounted for 24% and 8% of events. In the dabigatran group, 63% (n = 24) of the events were mild bleeding and 31% (n = 12) were moderately severe bleeding. In the warfarin group, mild bleeding was reported in 56% (n = 34) of patients with a bleeding event, and moderately severe bleeding in 41% (n = 25) of patients. Severe bleeding occurred in 2 patients in each group. Dose reduction or discontinuation was necessary in 18% of dabigatran patients and 16% of warfarin patients. None of the patients experienced recurrence of deep vein thrombosis.

A total of 270 patients (135 in each group) used oral contraceptives during anticoagulation therapy. This was not associated with recurrence of deep vein thrombosis (OR 0.59; 95% CI 0.20–1.72) or abnormal uterine bleeding (OR 1.14; 95% CI 0.70–1.86), with comparable results in both groups.

Conclusion

The study results indicate that the use of dabigatran as anticoagulation therapy for deep vein thrombosis is associated with a significantly lower risk of abnormal uterine bleeding compared to the use of warfarin. Further studies will be necessary to confirm these findings. Additionally, oral contraceptives can be continued during anticoagulation therapy for both pregnancy prevention and treatment of menorrhagia.

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Source: Huisman M. V., Ferreira M., Feuring M. et al. Less abnormal uterine bleeding with dabigatran than warfarin in women treated for acute venous thromboembolism. J Thromb Haemost 2018; 16 (9): 1775–1778, doi: 10.1111/jth.14226.