Rivaroxaban may increase the risk of severe abnormal uterine bleeding compared with other direct oral anticoagulants (DOACs) or warfarin, according to the findings of a retrospective study recently published in Drug Safety.

To assess whether anticoagulant therapy increases the risk of severe abnormal uterine bleeding, study authors utilized the FDA’s Sentinel System (10/2010-09/2015) to obtain data on females over 18 years old with a history of venous thromboembolism or atrial flutter/fibrillation who had recently initiated a DOAC or warfarin.

“We followed women from dispensing date until the earliest of transfusion or surgery following vaginal bleeding, disenrollment, exposure or study end date, or recorded death,” the authors explained. “We estimated hazard ratios (HRs) using Cox proportional hazards regression via propensity score stratification.” Additionally, the authors conducted 4 pairwise comparisons for each intervention.

Study findings revealed an increased risk of surgical intervention in women exposed to rivaroxaban compared with those exposed to dabigatran (HR, 1.19; 95% CI, 1.03-1.38), apixaban (HR, 1.23; 95% CI, 1.04-1.47), and warfarin (HR, 1.34; 95% CI, 1.22-1.47). For the dabigatran/apixaban comparisons, no difference was observed when assessing the risk of surgical intervention. It was noted that the risk of transfusion was only found to be increased when comparing rivaroxaban and dabigatran (HR, 1.49; 95% CI, 1.03-2.17).

Exposure to rivaroxaban was also associated with an increased risk of surgical intervention in patients without underlying gynecological conditions when compared with dabigatran (HR, 1.22; 95% CI, 1.05-1.42), apixaban (HR, 1.25; 95% CI, 1.04-1.49), and warfarin (HR, 1.36; 95% CI, 1.23-1.50).

Based on their findings, the authors concluded that women of reproductive age on anticoagulant therapy should be made aware of the potential risk of severe abnormal uterine bleeding.


Eworuke E, Hou L, Zhang R, et al. Risk of severe abnormal uterine bleeding associated with rivaroxaban compared with apixaban, dabigatran and warfarin. Drug Safety. Published May 20, 2021. doi: 10.1007/s40264-021-01072-0