Introduction: Antithrombotic therapies are associated with increased bleeding risk. Abnormal uterine bleeding data have been reported in clinical trials of patients with venous thromboembolism (VTE), but data are limited for patients with atrial fibrillation (AF).
Objective: Using real-world data from 4 US healthcare databases (October 2010 to December 2018), we compared the occurrence of severe uterine bleeding among women newly exposed to rivaroxaban, apixaban, dabigatran, and warfarin stratified by indication.
Methods: To reduce potential confounding, patients in comparative cohorts were matched on propensity scores (PS). Treatment effect estimates were generated using Cox proportional hazard models for each indication, in each database, and only for pairwise comparisons that met a priori study diagnostics. If estimates were homogeneous (I2 <40%), meta-analysis across databases was performed and pooled hazard ratios (HR) reported.
Results: Data from 363,919 women newly exposed to a DOAC or warfarin with a prior diagnosis of AF (60.8%) or VTE (39.2%) were analyzed. Overall incidence of severe uterine bleeding was low in the populations exposed to direct oral anticoagulants (DOACs), although relatively higher in the younger VTE population versus the AF population (unadjusted incidence rates: 2.8-33.7 vs 1.9-10.0 events/1,000 person-years). In the PS-matched AF population, a suggestive, moderately increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin (HRs and 95% confidence intervals ranging from 0.83 [0.27-2.48] to 2.84 [1.32-6.23] across databases with significant heterogeneity), apixaban (pooled HR: 1.45 [0.91-2.28]), and dabigatran (2.12 [1.01-4.43]), which were sensitive to the time-at-risk period. In the PS-matched VTE population, a consistent, increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin (2.03 [1.19-3.27]) and apixaban (2.25 [1.45-3.41]), which were insensitive to the time-at-risk period.
Conclusion: For women who need antithrombotic therapy, personalized management strategies with careful evaluation of benefits and risks are required.
Below are links for study-related artifacts that have been made available as part of this study: