(B-068) Impact of andexanet alfa introduction on mortality and thromboembolic events, before and after Tuscan guidelines, in patients treated with rivaroxaban or apixaban with major bleeding

Background: The Tuscany Region (RT) has implemented guidelines for the use of andexanet alfa (AA) to support emergency room decisions and restrict its use to specific cases.

Objectives: To assess the impact of these guidelines on mortality and the occurrence of thromboembolic events in Tuscan patients treated with apixaban or rivaroxaban who experienced major bleeding.

Methods: We conducted a retrospective ecological cohort study using health administrative data stored by ARS Toscana. All individuals registered in the inhabitant registry and treated with rivaroxaban or apixaban were observed (2018/1/1 and 2024/8/1) for major bleeding occurrence. The study period was divided into: (1) 2018/1/1-2020/3/8 and 2021/6/22-2021/8/31 (AA unavailable in RT, excluding the COVID19 emergency), (2) 01/09/2021-31/07/2023 (AA available pre-guidelines), (3) 2023/8/1-2024/6/30 (AA available with guidelines). Major bleeding was defined per the International Society on Thrombosis and Haemostasis and previous validation studies. Within 30 days after bleeding, we observed the occurrence of thromboembolic events (myocardial infarction, ischemic stroke, deep vein thrombosis, transient ischemic attack, pulmonary embolism) or death (mortality data until 2024/1/1). Age-standardized bleeding incidence and time to event (death/thromboembolic event), with corresponding interquartile range (IQR), were analyzed. Also, monthly dispensation of AA was described.

Results: Among 99,083 individuals treated with rivaroxaban or apixaban, 1,366 episodes of major bleeding occurred (449, 471, 106 in the three periods), primarily in males (54.4%) with a mean age at bleeding of 81 years (81.4, 81, 81.5 in the three periods, respectively). Thromboembolic events at 30 days were more frequent in period 3 (4.7%) vs. period 1 (2.9%) and 2 (2.1%). Mortality was 20.7%, with a median of 6 days (IQR 6-12): 17.6% in period 1 (6 days, IQR 2-11.5), 22.7% in period 2 (7 days, IQR 2-15), and 19.8% in period 3 (4 days, 1-7). Monthly AA dispensation averaged 7.4 in period 2 and 6.2 in period 3.

Conclusions: Preliminary results of this study showed that, while no further increase in mortality was observed after the introduction of the guidelines, thromboembolic events occurrence did rise and will be further analyzed. Additionally, and contrary to expectations, mortality increased after introduction of AA. This result warrants further investigation.