UMEM Educational Pearls

Title: Andexanet Alfa vs. 4F-PCC for FXa Inhibitor-Related ICH (in collaboration with Castin Schulz, PharmD)

Category: Pharmacology & Therapeutics

Keywords: andexanet alfa, 4F-PCC, Kcentra, ICH, thrombosis (PubMed Search)

Posted: 11/13/2025 by Wesley Oliver (Updated: 12/5/2025)
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This pearl was adapted from a literature update presented by Castin Schulz, PharmD on November 13, 2025.

A 2025 study in the American Journal of Emergency Medicine provides new real-world data on the two most common reversal agents for factor Xa (fXa) inhibitor-related intracranial hemorrhage (ICH).

This national retrospective cohort study evaluated 350 Veterans who received either andexanet alfa (AA) or 4-factor prothrombin complex concentrate (4F-PCC) for fXa inhibitor-related ICH.

Key Findings (Propensity-Matched Analysis)

Effectiveness (Mortality): There was no significant difference in the primary effectiveness endpoint of 90-day mortality between the two groups.
- AA Group: 30.9% mortality
- 4F-PCC Group: 36.6% mortality
- (p=0.35)
Safety (Thrombosis): The AA group experienced a significantly higher rate of 30-day thrombotic events.
- AA Group: 11.4% thrombotic events
- 4F-PCC Group: 2.4% thrombotic events
- (p<0.01)
Specific Risk: The primary driver for this difference was a significantly higher rate of acute ischemic stroke (AIS) in the AA group (6.5% vs. 0.8%, p=0.02).

Clinical Takeaway

In this study of Veterans with fXa inhibitor-related ICH, andexanet alfa did not improve 90-day mortality compared to 4F-PCC. However, its use was associated with a significantly increased risk of 30-day thrombotic events, particularly ischemic stroke.

This study adds to a growing body of literature questioning the safety profile of AA. The authors conclude that the selection of AA should be carefully weighed against the patient's underlying risk of thrombotic events.

References

Rech MA, Budde E, Evans CT, et al. Andexanet alfa increases 30-day thrombotic events relative to four-factor prothrombin complex concentrate for factor Xa inhibitors-related intracerebral hemorrhage in veterans. Am J Emerg Med. 2025;97:97-102. doi:10.1016/j.ajem.2025.07.037