Effects of long-term Antiepileptic Drug Monotherapy on All-cause Death in Patients with Post-Stroke Epilepsy: A Nationwide Population-based Study

Objective: We aim to compare the effect of long-term antiepileptic drug (AED) monotherapy on the risk of death and recurrent ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and Methods We identified all hospitalized patients (≥20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohorts were defined as the stroke patients (1) who had no epilepsy and no AEDs use before the index stroke, and (2) who had epilepsy and AEDs use after 14 days from the stroke onset. The PSE patients receiving AED monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new AED groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of death and recurrent ischemic stroke within 5 years across all groups, using the new AED group as the reference. Results: Of 6962 PSE patients using AED monotherapy, 3917 (56%) were on phenytoin, 1623 (23%) on valproic acid, 457 (7%) on carbamazepine, and 965 (14%) on new AEDs. After adjusting for confounders, compared with new AED users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95% CI: 1.06-2.55). On the other hand, all AED groups showed a similar risk of recurrent ischemic stroke. Conclusion: Among PSE patients on first-line monotherapy, compared to new AEDs, use of phenytoin was associated with a higher risk of death in 5 years.