ArticleNeurology and therapy2025
Safety and Effectiveness of Direct Oral Anticoagulants in Combination with Antiseizure Medications: Protocol for a Systematic Review and Meta-analysis.
Article in Neurology and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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
1 citing paper in PubMed.
- Utilization of Apixaban Pharmacokinetics for Dose Optimization in High-Risk Elderly Patients.Clinical pharmacokinetics · 2026Observational
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe concurrent use of direct oral anticoagulants (DOACs) and antiseizure medications (ASMs) is increasingly common, particularly among patients with atrial fibrillation, stroke, and epilepsy. Certain ASMs may affect the pharmacokinetics of DOACs through enzyme induction or modulation of P-glycoprotein, potentially altering their effectiveness and safety. However, evidence regarding these interactions and their impact on clinical outcomes remains limited, heterogeneous, and inconsistently reported. The objective of this systematic review is to synthesize current evidence on cerebrovascular outcomes, bleeding risk, and pharmacokinetic effects in patients treated concurrently with DOACs and ASMs.
methodsThis protocol outlines a systematic review and meta-analysis of randomized controlled trials, observational studies, case-control studies, and pharmacokinetic investigations involving patients aged 8 years or older treated with DOACs in combination with ASMs. Databases including MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) will be searched without language restrictions. Additional studies will be identified via reference screening, expert contact, and AI-assisted evidence discovery (Elicit). Dual independent review will be applied for study selection, data extraction, and risk of bias assessment using validated tools (Newcastle-Ottawa Scale (NOS), the Quality In Prognosis Studies (QUIPS) tool, and the Cochrane Risk of Bias 2.0 tool). Where appropriate, meta-analysis will be performed using random-effects models; otherwise, results will be synthesized narratively in accordance with SWiM (Synthesis Without Meta-analysis) guidelines. PLANNED OUTCOMES: Primary effectiveness outcome: composite of ischemic stroke and systemic embolism (IS/SE). SECONDARY OUTCOMES: ischemic stroke alone, systemic embolism alone, transient ischemic attack (TIA), major bleeding, intracranial hemorrhage, pharmacokinetic measures, and seizure occurrence. Subgroup analyses will stratify by ASM type, pharmacokinetic interaction potential, age groups (8-17, ≥ 18 years), and DOAC indications (e.g., non-valvular atrial fibrillation, venous thromboembolism, left ventricular thrombus). An individual participant data (IPD) meta-analysis is planned if sufficient eligible data are available. A summary table of outcomes and definitions (Table 1) and an overview flow diagram of the planned process (Fig. 1) are provided. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4201050986.
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