(170) FACTOR XA INHIBITOR–RELATED MAJOR BLEEDING EVENTS IN THE NETHERLANDS

Background: Despite the lower bleeding risk of oral factor Xa inhibitors (FXai) compared to vitamin K antagonists, the risk of major bleeding complications of FXai is still very substantial and associated with significant morbidity and mortality.

Objectives: To explore the incidence of major bleeding following initial FXai use, by bleeding type, FXai type and rates over time.

Methods: A retrospective observational cohort study was conducted using the PHARMO Data Network in the Netherlands, and involved an analysis of new oral FXai users (i.e. apixaban, edoxaban or rivaroxaban) between 1 January 2008 (date of first approval of FXai in the Netherlands) and 31 December 2021 (last date of data collection). Adult patients with a FXai dispensing for a therapeutic indication (i.e. venous thromboembolism, atrial fibrillation (AF), non-mechanical cardiac-valve replacement) and without a recent major bleeding (≤60 days before initial FXai use) were included. Incidence rates of major bleeding were assessed over time and reported 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. No formal comparisons were analysed.

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% of the patients were male. The most common FXai indication among the study patients was AF (78%). A total of 349 patients were observed with major bleeding, 107 patients had GIBs and 42 patients had ICHs. 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 initial FXai use, respectively. These incidence rates were highest at 1 month and decreased over time for all FXai included. Per FXai type, crude incidence rates of major bleedings were 1.24, 1.84 and 2.27 per 100 PY in 3 years for new apixaban users, rivaroxaban users and edoxaban users, respectively.

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