6G-02 - Levetiracetam Use and Dementia Risk in Patients with Post-Stroke Seizures: A Population-Based Study Using a Target Trial Emulation Framework

Background: Patients with post-stroke seizures, a common complication of stroke, face a higher risk of developing dementia compared to those without seizures. Levetiracetam is commonly prescribed for post-stroke seizures, however, the impact of levetiracetam use on long-term dementia risk in this patient population remains unclear.

Objectives: To understand the dementia risk associated with levetiracetam versus valproic acid in patients with post-stroke seizures.

Methods: Using data from Taiwan’s Health and Welfare Database, this retrospective cohort study followed the target trial emulation framework to emulate a hypothetical randomized trial estimating the effect of levetiracetam on the risk of dementia. Eligible patients were those who were hospitalized for their first seizure event between 2012 and 2020 and newly initiated levetiracetam or valproic acid before discharge; they also had at least one inpatient stroke diagnosis within the two years prior to the first seizure event. Patients were excluded if they had dementia diagnosis or anti-dementia drug use within six months before the discharge date. Patients were followed from discharge date until the occurrence of outcomes of interest [(1) new-onset dementia, (2) initiation of anti-dementia drugs, and (3) a composite dementia-related outcome – either a new-onset dementia diagnosis or the initiation of anti-dementia drugs], death, or end of study period (2020), whichever occurred first. We estimated the effect of initiating levetiracetam on dementia risk using cox proportional hazards models with inverse probability treatment weighting to adjust for baseline confounding.

Results: The observational cohort included 937 (50.2%) levetiracetam users and 929 (49.8%) valproic acid users. After weighting, levetiracetam use was associated with increased risks of initiating anti-dementia drugs (HR: 1.51; 95% CI: 1.07–2.12) and composite dementia-related outcome (HR: 1.26; 95% CI: 1.05–1.50) compared to valproic acid use. However, no statistically significant difference was observed in the risk of new-onset dementia alone between the two drug groups (HR: 1.1; 95% CI: 0.90–1.34).

Conclusions: Levetiracetam use was associated with a higher likelihood of initiating anti-dementia drugs and an increased risk of composite dementia-related outcome, suggesting a possible link to cognitive decline. Careful monitoring of cognitive function is recommended for patients with post-stroke seizures who are treated with levetiracetam.