Andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage: the prospective observational multicenter ASTRO-DE study.

Background: Hematoma expansion after intracranial hemorrhage (ICH) in anticoagulated patients signifi-cantly influences clinical outcomes and mortality, emphasizing the need for effective reversal agents. Andexanet alfa is a specific reversal agent for factor Xa associated major bleeding.

Aims: The ASTRO-DE study collected real-world evidence on the effect of andexanet alfa on mitigat-ing hematoma expansion and altering prognosis in rivaroxaban- or apixaban-treated patients with ICH.

Methods: ASTRO-DE was a prospective non-interventional cohort study conducted at 25 certified stroke centers in Germany. The primary outcome was the hematoma volume change and the propor-tion of patients with hematoma growth ≤33% within 12-72 h or until first control imaging. Sec-ondary endpoints included in-hospital thromboembolic events and mortality up to 90 days.

Results: A total of 137 patients (47.4% male, mean age 80.0 years) with ICH (92.6% spontaneous, 87.4% intracerebral), mean NIHSS on admission of 11.2 points, and mean initial hematoma volume of 26.5 mL (median: 14.1 mL) were analyzed. Ninety patients (65.7%) suffered ICH while treated with apixaban and 47 (34.3%) with rivaroxaban. The median time between symptom onset and application of andexanet alfa was 3.3 h, door-to-needle time was 1.3 h. The mean change in hematoma volume until the first control imaging, conducted after a median of 15.6 h, was 2.3 mL (95% CI: 0.4 to 4.2), while the change within 12-72 h was 1.8 mL (95% CI: 0.4 to 3.2). Hema-toma growth ≤33% was achieved in 90.3% of the 93 evaluable patients based on first control imaging and in 90.5% of the 63 evaluable patients, considering only imaging performed within the 12-72 h window. During hospitalization, death occurred in 30/137 patients (21.9%) and 17 thromboembolic events in 11/137 (8.0%) patients. The 90-day-mortality was 47/128 (36.7%).

Conclusions: ASTRO-DE is the first prospective observational study systematically collecting standardized clinical routine data with andexanet alfa treatment. The study demonstrated favorable hemo-stasis and minimal mean hematoma volume growth in patients with ICH associated with apixa-ban or rivaroxaban treatment.