Evaluating Antiseizure Medication Selection and Cardiovascular Outcomes During DOAC Therapy

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  JAMA Neurology. https://doi.org/10.1001/jamaneurol.2026.2712 
Dr. Kai Michael Schubert et al.

Points

University of Liverpool and Zurich researchers evaluated electronic health records from over two million adults with epilepsy to assess clinical risks associated with concomitant antiseizure and anticoagulant therapy.
Real world data from over nine thousand patients revealed that taking levetiracetam alongside direct oral anticoagulants was associated with nearly double the risk of serious blood clots.
Patients prescribed levetiracetam and direct oral anticoagulants exhibited a sixty percent higher risk of all cause mortality compared to those taking alternative non-inducing antiseizure medications.
Older enzyme-inducing antiseizure medications like carbamazepine and phenytoin showed a fifty-five percent higher thromboembolism risk and thirty-eight percent lower major bleeding risk due to accelerated drug breakdown.
Study authors noted these observational results represent a critical safety signal rather than definitive causality, advising patients to maintain current drug regimens while regulatory bodies review the findings.

Summary

This real-world observational study evaluated clinical outcomes associated with concomitant antiseizure medication (ASM) and direct oral anticoagulant (DOAC) therapy in adults with epilepsy. Led by researchers from the University of Liverpool and the University of Zurich, the investigation analyzed anonymized electronic health records across 165 healthcare organizations within the international TriNetX network. Out of a pool of over 2.29 million adults with epilepsy, researchers identified 9,529 patients who initiated an ASM while receiving DOAC therapy, assessing comparative risks of thromboembolism, major bleeding, and all-cause mortality.

The majority of the study population (57%) received levetiracetam. Comparative analyses demonstrated that co-prescription of levetiracetam with DOACs was associated with almost twice the risk of thromboembolic events—such as stroke, myocardial infarction, or systemic embolism—compared with alternative non-enzyme-inducing ASMs like lamotrigine or lacosamide. Additionally, patients treated with levetiracetam experienced a 60% higher risk of all-cause mortality, though no statistically significant difference in major bleeding risk was observed between cohorts.

Evaluating enzyme-inducing ASMs, including carbamazepine and phenytoin, confirmed a 55% higher risk of thromboembolic events and a 38% lower risk of major bleeding compared to non-inducing comparator agents. These findings suggest that levetiracetam, traditionally preferred due to its presumed lack of metabolic drug interactions, presents a novel safety signal when combined with DOACs. The authors concluded that ASM selection represents a crucial, modifiable risk factor in patients with epilepsy requiring anticoagulation, warranting further mechanistic research and clinical vigilance.

Link to the article: https://jamanetwork.com/journals/jamaneurology/article-abstract/2853050#google_vignette

References

Schubert, K. M., Ferreira-Atuesta, C., Soma, A., Zelano, J., Seiffge, D. J., Brigo, F., Trinka, E., Mishra, N. K., Russo, E., Lip, G. Y. H., Mbizvo, G. K., & Galovic, M. (2026). Safety of antiseizure medications during direct oral anticoagulant therapy in epilepsy. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2026.2712