Risk of thromboembolic events in patients co-treated with factor Xa-inhibiting direct oral anticoagulants and anti-seizure medications: insights from pharmacovigilance data.

BACKGROUND

Limited data have raised concerns about an increased risk of thromboembolic adverse events in atrial fibrillation (AF) patients co-treated with factor Xa-inhibiting direct oral anticoagulants (FXa-DOACs) and anti-seizure medications (ASMs). However, evidence regarding this association remains controversial.

OBJECTIVES

This study aims to investigate the impact of ASMs on the reporting of thromboembolic events in FXa-DOAC-treated patients.

METHODS

This study analyzed data from the FDA Adverse Event Reporting System (FAERS) between 2011Q3 and 2024Q1 using the weighted composite score integrated by four pharmacovigilance signals [reporting odds ratio (ROR), Empirical Bayes Geometric Mean (EBGM), additive model and multiplicative model].

RESULTS

A total of 177 cases of thromboembolic events were identified in patients using combined FXa-DOACs and ASMs. Levetiracetam together with FXa-DOACs was associated with an increased risk of thromboembolic events, particularly apixaban (ROR: 2.29, 95%CI 1.56-3.38; EBGM05:1.32; additive model:0.14 > 0; multiplicative mode: 2.47 > 1;composite score:1) and rivaroxaban (ROR:3.81, 95% CI 2.77-5.26; EBGM05:1.99; additive model:0.13; multiplicative model:1.71; composite score:1). Valproic acid was associated with thromboembolic risk when with rivaroxaban (ROR:4.80, 95%CI 2.50-9.19; EBGM05:1.64; additive model:0.29; multiplicative model:8.48; composite score:1).

CONCLUSION

This study suggests that the concomitant use of levetiracetam and valproic acid with FXa-DOACs is associated with an increased risk of thromboembolic events.