OBJECTIVES: The risk of factor Xa inhibitor (FXai)-related major bleeding is substantial and associated with significant morbidity and mortality. This research explored incidence of major bleeding following new FXai use, by bleeding type, FXai type and over time.

METHODS: A retrospective observational cohort study was conducted using the PHARMO Data Network in the Netherlands, analysing new oral FXai users between 2008 and 2021. Adult patients with a FXai dispensing for a therapeutic indication (venous thromboembolism, atrial fibrillation (AF), non-mechanical cardiac-valve replacement) and without a recent major bleeding (≤60 days before FXai initiation) were included. Incidence rates of major bleeding were assessed over time per 100 person years (PY). Results were stratified by type of bleeding (e.g. gastro-intestinal bleedings [GIB] and intracranial haemorrhage [ICH]), type of FXai, and analysed over time.

RESULTS: In this study, 17,822 new FXai users were included, of whom 7,043 used apixaban, 1,967 edoxaban and 8,812 rivaroxaban. The mean (SD) age of patients was 71 (12) years and 56% was male. The most common FXai indication was AF (78%). A total of 349 patients were observed with major bleeding. Incidence rates of all major bleeding, GIB and ICH were 1.65, 0.50 and 0.20 per 100 PY in the 3 years after FXai initiation, respectively. Rates were highest at 1 month and decreased over time for all FXai. Per FXai type, crude incidence rates of major bleedings were 1.24, 1.84 and 2.27 per 100 PY in 3 years for apixaban, rivaroxaban and edoxaban, respectively.

CONCLUSIONS: Our study provided insight into the incidence of major bleeding in new FXai users. The highest incidence rate of bleeding was seen in edoxaban users, although no formal adjusted comparisons were made. The most common type of bleeding was GIB, and overall incidence rates were highest in the first month after initiating FXai.