Reversal of Factor Xa Inhibitor-Related Intracranial Hemorrhage: A Multicenter, Retrospective, Observational Study Comparing the Efficacy and Safety of Andexanet and Prothrombin Complex Concentrates

Crit Care Med. 2025 Jun 1;53(6):e1202-e1213. doi: 10.1097/CCM.0000000000006656. Epub 2025 Apr 1.

Abstract

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.

Keywords: andexanet; anticoagulation reversal; factor Xa inhibitors; intracranial hemorrhage; prothrombin complex concentrates.

Publication types

  • Multicenter Study
  • Observational Study
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Coagulation Factors* / adverse effects
  • Blood Coagulation Factors* / therapeutic use
  • Factor Xa Inhibitors* / adverse effects
  • Factor Xa Inhibitors* / therapeutic use
  • Factor Xa* / adverse effects
  • Factor Xa* / therapeutic use
  • Female
  • Humans
  • Intracranial Hemorrhages* / chemically induced
  • Intracranial Hemorrhages* / drug therapy
  • Male
  • Middle Aged
  • Pyrazoles / adverse effects
  • Pyridones / adverse effects
  • Recombinant Proteins* / therapeutic use
  • Retrospective Studies
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use
  • Treatment Outcome
  • United States

Substances

  • Factor Xa Inhibitors
  • prothrombin complex concentrates
  • Blood Coagulation Factors
  • Rivaroxaban
  • PRT064445
  • Factor Xa
  • Pyrazoles
  • apixaban
  • Recombinant Proteins
  • Pyridones