(C-239) Incidence of Severe Uterine Bleeding Following Exposure to Non-Vitamin K Antagonist Oral Anticoagulants in South Korea

Background: The U.S. FDA identified a risk of severe uterine bleeding (SUB) in women exposed to Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) based on sentinel study. However, the risk of SUB in women associated with NOACs use remains insufficient in South Korea.

Objectives: To better understand the occurrence of SUB in women treated with NOACs, we investigated the incidence of SUB compared with warfarin exposure.

Methods: A retrospective cohort study was conducted using the National Health Insurance Service (NHIS) and the common data model from the Medical record Observation and Assessment for drug safety (MOA). Adult women with a diagnosis of atrial fibrillation (AF) or deep vein thrombosis/pulmonary embolism (DVT/PE) in the 183 days before and on the day of dispensing of NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or warfarin were identified in the NHIS database from 2010 to 2023 and the MOA-CDM from 2013 to 2023. We excluded women who had undergone joint replacement surgery, transfusion, medical management, or surgical management. We followed women from their first anticoagulant dispensing date until the earliest of: discontinuation of study drugs, recorded death, end of the study period, or occurrence of SUB. SUB was categorized as (1) same-day red blood cell transfusion (transfusion) at the time of uterine bleeding diagnosis, or (2) surgical management occurring within 60 days of uterine bleeding diagnosis (surgical management). The incidence rate per 1,000 years was calculated to measure the absolute incidence of SUB in the exposed and comparator groups.

Results: We identified 281,327 and 33,874 new NOACs users and 103,084 and 9,128 new warfarin users in the NHIS and MOA-CDM respectively. Overall, NOAC users had similar incidence rates of SUB compared with warfarin users(2.32 vs 2.09; NHIS, 0.81 vs 0.72; MOA-CDM). When investigated by each active ingredient in NOACs, the rivaroxaban group had the highest SUB incidence rate compared with the warfarin group(4.02 vs 2.09; NHIS, 1.84 vs 0.72; MOA-CDM) while the dabigatran group had the lowest(0.97 vs 2.09; NHIS, 0.37 vs 0.72; MOA-CDM).

Conclusions: Our research showed a relatively increased incidence of SUB associated with rivaroxaban exposure. Further research is needed to assess the comparative risk.