ArticleCNS drugs2021
Effect of Enzyme-Inducing Antiseizure Medications on the Risk of Sub-Therapeutic Concentrations of Direct Oral Anticoagulants: A Retrospective Cohort Study.
Article in CNS drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 3 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Induction of cytochrome P450 2C9 and P-glycoprotein activity by antiseizure medications: A systematic review and network meta-analysis.Epileptic disorders : international epilepsy journal with videotape · 2026Pooled it
- 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2024Guideline
- Guideline
- Cardiovascular Effects of Antiseizure Medications for Epilepsy.CNS drugs · 2025Review
- The Effect of Levetiracetam Compared with Enzyme-Inducing Antiseizure Medications on Apixaban and Rivaroxaban Peak Plasma Concentrations.CNS drugs · 2024Observational
- Pilot study on the probability of drug-drug interactions among direct oral anticoagulants (DOACs) and antiseizure medications (ASMs): a clinical perspective.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study.CNS drugs · 2023Article
- Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment.CNS drugs · 2023Article
- Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation: A Structured Narrative Review.Clinical pharmacokinetics · 2023Review
- Thromboembolic Risks with Concurrent Direct Oral Anticoagulants and Antiseizure Medications: A Population-Based Analysis.CNS drugs · 2022Article
- Anticoagulant drug-drug interactions: Highlighting the need for antithrombotic stewardship and shared decision making.Research and practice in thrombosis and haemostasis · 2022Article
- Association Between Use of Pharmacokinetic-Interacting Drugs and Effectiveness and Safety of Direct Acting Oral Anticoagulants: Nested Case-Control Study.Clinical pharmacology and therapeutics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStroke and thromboembolic events occurring among patients taking direct oral anticoagulants (DOACs) have been associated with low concentrations of DOACs. Enzyme-inducing antiseizure medications (EI-ASMs) are associated with enhanced cytochrome-P450-mediated metabolism and enhanced P-glycoprotein-mediated transport.
objectiveThe aim of this study was to evaluate the effect of concomitant EI-ASM use on DOAC peak concentrations in patients treated in clinical care.
methodsWe performed a retrospective cohort study of patients treated with DOACs for atrial fibrillation and venous thromboembolic disease in an academic general hospital. In total, 307 patients treated with DOACs between August 2015 and January 2020 were reviewed. Clinical characteristics and peak DOAC plasma concentrations of patients co-treated with an EI-ASM were compared with those of patients not treated with an EI-ASM. An apixaban dose score (ADS) was defined to account for apixaban dosage and the number of apixaban dose-reduction criteria.
resultsIn total, 177 peak DOAC plasma concentrations (including apixaban, rivaroxaban, and dabigatran) from 131 patients were measured, including 24 patients co-treated with an EI-ASM and 107 controls not treated with an EI-ASM. The proportion of patients with DOAC concentrations below the expected range was significantly higher among EI-ASM users than among patients not taking an EI-ASM (37.5 vs. 9.3%, respectively; p = 0.0004; odds ratio 5.82; 95% confidence interval [CI] 2.03-16.66). Most of these patients were treated with apixaban (85%); however, sensitivity analysis results were also significant (p = 0.031) for patients with non-apixaban DOACs. In patients co-treated with apixaban and an EI-ASM, median apixaban peak concentration was 106 ng/mL (interquartile range [IQR] 71-181) compared with 150 ng/mL (IQR 94-222) in controls (p = 0.019). In multivariable analysis, EI-ASM use was associated with 6.26-fold increased odds for apixaban concentration below the expected range (95% CI 2.19-17.90; p = 0.001). Apixaban concentrations were significantly associated with EI-ASM use, moderate enzyme inhibitor use, and ADS.
conclusionsConcurrent EI-ASM and DOAC use presents a possible risk for DOAC concentrations below the expected range. The clinical significance of the interaction is currently unclear.
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