Andexanet alfa vs standard of care for factor Xa inhibitor-induced intracranial hemorrhage-a systematic review and meta-analysis.

BACKGROUND

Direct oral anticoagulants are activated factor (F)X (FXa) or thrombin inhibitors. Patients on FXa inhibitors are at increased risk for major bleeding events that require anticoagulation reversal. Andexanet alfa is a FXa inhibitor reversal agent, potentially offering better efficacy compared to standard of care options.

OBJECTIVES

To conduct a systematic review and meta-analysis comparing the efficacy and safety of andexanet alfa vs standard of care for reversing FXa inhibitor-induced intracranial hemorrhage.

METHODS

Random-effects meta-analysis. Ovid Medline, EMBASE, and CINAHL were searched from inception until February 1, 2025. Primary outcomes included hemostatic efficacy, thrombotic events, and mortality. Subgroup analyses isolated studies using 4-factor prothrombin complex concentrate as standard of care and the Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) trial's definitions of hemostatic efficacy.

RESULTS

A total of 3039 studies were identified, with 23 studies (1 randomized controlled trial, 452 participants; 22 nonrandomized, 4085 participants) included in the final analysis. Thirteen studies assessed hemostatic efficacy, with a pooled odds ratio of 1.68 (95% CI, 1.2, 2.36; P = .003; I 2 = 0%) favoring andexanet alfa over standard of care. Thirteen studies reported thrombotic events, with a pooled odds ratio of 0.97 (95% CI, 0.59, 1.60; P = .90; I 2 = 0%). Thirteen studies assessed mortality, noting a pooled odds ratio of 0.69 (95% CI, 0.50, 0.96; P = .03; I 2 = 27%) favoring the andexanet alfa group. Published randomized controlled trials showed similar hemostatic improvements but no mortality benefit and a higher rate of thrombotic events.

CONCLUSION

Our meta-analysis found low-certainty evidence supporting improved hemostatic efficacy with andexanet alfa compared with standard of care, with a decrease in mortality and no effect on thrombotic complications. Further randomized data is required to establish a conclusive clinical benefit favoring andexanet alfa.