An 18-month single-center observational study of real-world use of andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage

Abstract

Objective: Intracranial hemorrhage is a life threatening complication of factor Xa inhibitors. Except for results of the open-label, single-arm ANNEXA-4 study, published real-world utilization of andexanet alfa is limited. We present our experience with andexanet alfa use in factor Xa inhibitor associated intracranial hemorrhage. The objective of this study was to assess the hemostatic efficacy and safety following early implementation of andexanet alfa use in factor Xa inhibitor associated intracranial hemorrhage.

Methods: Single center, retrospective, observational study at a large community teaching hospital and Comprehensive Stroke Center. Consecutive patients with factor Xa inhibitor associated intracranial hemorrhage, spontaneous or traumatic, treated with andexanet alfa. Primary outcome was hemostatic efficacy established by categories of hematoma growth between baseline and follow-up head computerized tomography after andexanet alfa treatment. Safety outcomes included inpatient mortality and 30-day readmission due to a thromboembolic event. Consecutive factor Xa inhibitor associated intracranial hemorrhage treated with andexanet alfa presenting between June 2018 and December 2019 were included.

Results: Thirty-nine patients with mean age of 81.9 years and median baseline Glasgow Coma Score of 14 were evaluated. Median (IQR) baseline intracerebral hematoma volume was 7.1 mL (2.3-28.5), while baseline thickness for subdural hemorrhage was 12.5 mm (8.0-19.3). In 35 of 39 patients with repeat computerized tomography prior to surgical intervention, excellent/good hemostatic efficacy was seen in 29 (82.9%). Excluded from the hemostatic efficacy estimate were four trauma patients who underwent hematoma evacuation prior to repeat head computerized tomography, nevertheless they had excellent hemostatic effectiveness without perioperative complications or rebleeding. Four (10.3%) patients died during hospitalization and two (5.1%) thrombotic events were observed.

Conclusions: In this cohort of a real-world utilization of andexanet alfa for reversal of factor Xa inhibitors in patients presenting with intracranial hemorrhage, we observed a high excellent/good hemostatic efficacy rate and lower than reported inpatient mortality and 30-day readmission due to thromboembolism consistent with the findings reported in ANNEXA-4 study. Despite the lack of comparative group, our outcomes, most noticeably hemostatic efficacy and inpatient mortality are consistent with those reported in the literature.

Keywords: Andexanet; Anticoagulation; Hemorrhage; Intracranial; Reversal.