ArticleCNS drugs2022
Thromboembolic Risks with Concurrent Direct Oral Anticoagulants and Antiseizure Medications: A Population-Based Analysis.
Article in CNS drugs, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- An Observational Study of the Effect of Concomitant Levetiracetam on Apixaban Concentrations in a Hospital Cohort.Clinical and translational science · 2026Observational
- Decoding the causes of ischemic stroke despite ongoing oral anticoagulation and their clinical impact: the ASPERA-R study.Journal of neurology · 2026Article
- Post-stroke seizures: classification, risk prediction, and management.Frontiers in neurology · 2026Review
- Safety and Effectiveness of Direct Oral Anticoagulants in Combination with Antiseizure Medications: Protocol for a Systematic Review and Meta-analysis.Neurology and therapy · 2025Article
- Cardiovascular Effects of Antiseizure Medications for Epilepsy.CNS drugs · 2025Review
- Effect of the frequently used antiepileptic drugs carbamazepine, gabapentin, and pregabalin on the pharmacokinetics of edoxaban and other oral factor xa inhibitors in healthy volunteers.Frontiers in pharmacology · 2025Article
- Impact of levetiracetam on direct oral anticoagulant level and outcomes among older Asian patients with atrial fibrillation.Frontiers in pharmacology · 2025Article
- Trousseau syndrome: management of refractory VTE.Hematology. American Society of Hematology. Education Program · 2024Review
- [Pathogenesis and potential diagnostic biomarkers of atrial fibrillation in Chinese population: a study based on bioinfor-matics].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Article
- The Effect of Levetiracetam Compared with Enzyme-Inducing Antiseizure Medications on Apixaban and Rivaroxaban Peak Plasma Concentrations.CNS drugs · 2024Observational
- Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.JAMA network open · 2024Article
- Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study.CNS drugs · 2023Article
- Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.Neurology · 2023Article
- Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment.CNS drugs · 2023Article
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveDrug-drug interactions between direct oral anticoagulants (DOAC) and antiseizure medications via the cytochrome P450 (CYP) or the P-glycoprotein (P-gp) systems may lead to under-anticoagulation. The clinical relevance of these interactions is unclear. We aimed to elucidate the risk of thromboembolism with concurrent DOAC and CYP/P-gp modulating antiseizure medications.
methodsIn this propensity score-weighted population-based retrospective cohort study, we used competing risk regression analyses to determine the risks of ischemic stroke, venous thromboembolism, and death in DOAC recipients taking CYP/P-gp-modulating antiseizure medications (phenytoin, valproate, levetiracetam, carbamazepine, or phenobarbital) versus those taking CYP/P-gp-neutral antiseizure medications (pregabalin, gabapentin, or clobazam). We also performed secondary analyses for the epilepsy and atrial fibrillation subgroups.
resultsAmong DOAC users, CYP/P-gp-modulating antiseizure medications were collectively associated with an increased risk of ischemic stroke (adjusted hazard ratio 1.28, 95% confidence interval 1.05-1.57, p = 0.017). In addition, phenytoin (adjusted hazard ratio 1.34, 95% confidence interval 1.07-1.68, p = 0.011) and valproate (adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.74, p = 0.006) were associated with increased mortality. In the epilepsy subgroup, the risk of ischemic stroke and venous thromboembolism did not differ between CYP/P-gp-modulating and CYP/P-gp-neutral antiseizure medications.
conclusionsAlthough CYP/P-gp-modulating antiseizure medications were associated with an increased risk of ischemic stroke when paired with DOAC in the primary analysis, such a phenomenon was not found among patients with epilepsy who took phenytoin, valproate, or levetiracetam with DOAC. Therefore, these antiseizure medication options among patients with epilepsy with concurrent DOAC should not be restricted solely based on their potential drug-drug interactions. Yet, the increased mortality during concurrent use of DOAC with phenytoin or valproate might call for caution.
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