Evaluation of oral factor Xa inhibitor-associated extracranial bleeding reversal with andexanet alfa

Abstract

Introduction: A reversal agent for factor Xa (FXa) inhibitors, andexanet alfa, was Food and Drug Administration approved without extensive study of clinical effectiveness, due to an overwhelming demand for FXa inhibitor reversal. In this study, we aimed to describe patient selection, clinical effectiveness, and safety of FXa inhibitor reversal with andexanet alfa in patients presenting with extracranial bleeding.

Methods: Consecutive patients who received andexanet alfa for reversal of FXa inhibitor-associated extracranial hemorrhage were identified. The primary outcome of interest was hemostatic efficacy, assessed using the Sarode et al criteria. Secondary outcomes of interest included incidence of thrombotic episodes post-reversal until discharge and in-hospital mortality.

Results: Twenty-one patients met the inclusion criteria (61.9% male, mean age: 73 years). Anticoagulation reversal with andexanet alfa was deemed effective (excellent [n = 3], good [n = 7]) in 10 (47.6%) patients, and poor in 11 patients (52.4%). Eight (38.1%) patients died, of which three were surgically managed, with all causes of death attributed to hemorrhage. Six ischemic complications occurred in four patients (19.0%); ischemic stroke (n = 2], pulmonary embolism (n = 1), deep vein thrombosis (n = 1), liver ischemia (n = 1), and bowel ischemia (n = 1).

Conclusion: We report poor overall outcomes, a low rate of hemostatic effectiveness, and a high rate of ischemic complications and mortality in this retrospective analysis of oral FXa inhibitor reversal with andexanet alfa for extracranial bleeds. More rigorous epidemiological, and ideally randomized studies, are needed to determine the role of andexanet alfa for FXa inhibitor-associated bleeding for extracranial hemorrhages, where large variation in severity and presentation exists.

Keywords: PRT064445; factor Xa inhibitors; hemorrhage; hemostasis; treatment outcome.