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 significantly 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 Andexanet alfa: non-interventional study at STROke centers in Germany (Deutschland, DE) (ASTRO-DE) study collected real-world evidence on the effect of andexanet alfa on mitigating 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 proportion of patients with hematoma growth ⩽33% within 12-72 h or until first control imaging. Secondary 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 National Institutes of Health Stroke Scale (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 1.1 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% confidence interval (CI) = 0.4-4.2), while the change within 12-72 h was 1.8 mL (95% CI = 0.4-3.2). Hematoma 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%).

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

Data access statement: Data are available upon reasonable request by contacting the corresponding author.