OBJECTIVE: To determine the effectiveness and safety of andexanet and prothrombin complex concentrates (PCCs) when administered after intracranial hemorrhage (ICrH) associated with direct oral anticoagulants, specifically apixaban or rivaroxaban.

DESIGN: A multicenter, retrospective, observational study of patients with apixaban or rivaroxaban-related ICrH who received andexanet or PCCs between January 1, 2015, and March 31, 2023. A predefined sensitivity analysis excluding patients with an admission Glasgow Coma Scale score of less than 7 was also performed.

SETTING: Forty-two stroke centers in the United States.

PATIENTS: A total of 1133 patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary efficacy outcome was the percentage of patients with excellent or good hemostasis as defined by the modified Sarode criteria. The primary safety outcome was the occurrence of a thrombotic event (TE) during their hospital stay. Of the 1133 patients evaluated, 1096 were included. In the full hemostatic efficacy analysis, patients receiving andexanet (87.8%) had higher odds of achieving excellent or good hemostasis (odds ratio [OR] 1.60; 95% CI, 1.00-2.56; p = 0.048) compared with PCCs (81.8%). Patients treated with andexanet (7.9%) had higher odds of a TE (OR 1.91; 95% CI, 1.13-3.20; p = 0.014) compared to those treated with PCCs (4.2%). No differences in hemostatic or thrombotic outcomes were observed when the sensitivity analysis was applied.

CONCLUSIONS: Despite statistically higher odds of achieving hemostatic efficacy with andexanet, we also observed higher odds of a TE with no difference in discharge outcomes observed between groups. When those with more severe neurologic injuries were excluded, efficacy and safety outcomes were similar between treatments.