Oral anticoagulant drugs and CNS-related hematomas: a pharmacovigilance analysis from the FAERS database

Objective

Central nervous system (CNS)-related hematoma adverse events (hAEs) are serious and devastating complications in patients receiving oral anticoagulant (OAC) therapy. We aimed to analyze and characterize the risk of CNS-related hAEs across different OACs.

Methods

We analyzed CNS-related hAEs from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted to identify signals for each OAC. Logistic regression was used to assess mortality risk factors, while time-to-onset analysis characterized temporal patterns.

Results

A total of 5501 patients and 5641 CNS-related hAE reports were associated with OACs. Disproportionality analysis identified positive signals for all OACs, with warfarin showing the highest association (reporting odds ratio [ROR] = 38.31), followed by dabigatran (ROR = 22.76), rivaroxaban (ROR = 20.51), edoxaban (ROR = 16.81), and apixaban (ROR = 12.53). Subdural hematoma was the most frequently reported type (74.0 %). In multivariate analysis, age ≥75 years, weight <60 kg, multiple adverse events (AEs), and concomitant antidepressant use were independent predictors of mortality. All OACs exhibited early failure-type temporal profiles, with warfarin demonstrating a significantly longer median onset time (435.5 days) compared to non-vitamin K antagonist oral anticoagulants (NOACs, 158.5–228.0 days; P < 0.001).

Conclusion

OACs are associated with CNS-related hematomas, with varying risk profiles among agents. Advanced age, low body weight, multiple AEs, and concomitant antidepressant use are crucial mortality risk factors. CNS-related hAEs typically occur early during treatment. These findings provide insights for optimizing risk management and support appropriate anticoagulation when clinically indicated.