Work

Stroke and Thrombotic Events Associated With Concomitant Use of Oral Anticoagulants and Antiepileptic Drugs in the United States and Japan

Year: 2025

Type: article

Abstract: INTRODUCTION: Direct oral anticoagulants (DOACs) are substrates of efflux P-glycoprotein (P-gp) transporters, and the hepatic enzyme cytochrome P450 plays an important role. Antiepileptic drugs (AEDs) may reduce absorption or increase the metabolism of DOACs, thereby reducing their antithrombotic efficacy. However, there is no evidence that concurrent use of metabolic inducers in patients taking DOACs is associated with an increased risk of stroke or thrombotic events. METHODS: We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2010 to June 2023 and the Japanese Adverse Drug Event Report (JADER) database to April 2023. We compared the proportion of cases reporting thromboembolic and ischemic adverse events with the concomitant use of DOACs and first-generation drugs, such as phenytoin, metabolically inducing AEDs, to the proportion of cases with DOACs and control AEDs, such as levetiracetam. RESULTS: Compared with control AEDs, first-generation AEDs were associated with increased odds of reporting outcomes (reporting odds ratio {ROR}: 1.79, 95% confidence interval {CI}: 1.52-2.10, p<0.0001). Dabigatran, rivaroxaban, and apixaban were also similarly associated with increased reporting of outcome (ROR: 1.74, 95% CI: 1.26-2.39, ROR: 1.58, 95% CI: 1.24-2.02, and ROR: 2.07, 95% CI: 1.48-2.90). Edoxaban and JADER scores were not associated with patient outcomes. CONCLUSION: We observed an increase in the odds of reporting anticoagulation treatment failure among patients treated with DOACs and concomitant first-generation AEDs compared to those treated with control AEDs in the FAERS database. Care should be taken when administering dabigatran, apixaban, and rivaroxaban.

Source: Cureus

DOI: 10.7759/cureus.83268

Authors: Tomiko Sunaga, Ryo Yonezawa

Institutions: Hoshi University, SHOWA Medical University

Language: English

Topic: Atrial Fibrillation Management and Outcomes

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W4409962722