Category: Professional Posters
Purpose: Andexanet alfa (coagulation factor Xa [recombinant] inactivated-zhzo) is a recombinant modified human Factor Xa (FXa) decoy protein developed to specifically reverse the anticoagulant effect of FXa inhibitors. This study evaluated the hemostatic efficacy and anti-FXa reversal with andexanet in patients with spontaneous intracranial hemorrhage (ICrH).
Methods: The ANNEXA-4 study was a single-arm, prospective, open-label study of andexanet in patients presenting with major bleeding within 18 hours after taking either apixaban, rivaroxaban, edoxaban, or enoxaparin. We performed a subgroup analysis of patients with spontaneous (nontraumatic) ICrH. Brain imaging was performed at baseline, and at 1 and 12 hours post andexanet treatment. Subdural hemorrhage (SDH) and subarachnoid hemorrhage (SAH) thickness and intracerebral volumetric analysis were performed using Quantomo software. Patients were considered evaluable for efficacy if they had a baseline anti-FXa activity ≥75 ng/mL (≥0.25 IU/mL for enoxaparin-treated patients). The co-primary efficacy outcomes were change in anti-FXa and the proportion of patients with excellent or good hemostatic efficacy (defined as volume or thickness increase from baseline ≤35%) at 12 hours.
Results: Of 352 patients enrolled in ANNEXA-4, nontraumatic ICrH was present in 128 patients, including intracerebral +/- intraventricular ICrH in 99 patients, SAH in 5 patients, and SDH in 14 patients. In this cohort, the mean age was 78 years (SD 9.2); the median time from last FXa inhibitor dose to andexanet administration was 11.9 hours (IQR 7.9-15.3); the median time from symptoms to CT was 2.6 hours (IQR 1.2-2.7); and the median time from CT to andexanet administration was 1.8 hours (IQR 3.8-17.5). The median intraparenchymal volume in intracerebral bleeds was 9.5 mL (IQR 3.9-21.3).
Among 99 patients evaluable for efficacy, excellent or good hemostasis occurred in 77 (79%; 95% CI 70-87) patients at 12 hours post-treatment overall. The median reduction in anti-FXa activity in apixaban- and rivaroxaban-treated patients was 93.5% (IQR 91.4-95.1) and 93.0% (IQR 90.4-95.3), respectively. Within 30 days, thrombotic events occurred in 14 (10.9%) of 128 patients, and death occurred in 24 (18.8%) of 128 patients.
Conclusion: Andexanet reduced anti-FXa activity in patients with nontraumatic intracranial bleeding related to FXa inhibitor use and had a high rate of hemostatic efficacy up to 12 hours after treatment.