Abstract DP142: Settling the Debate: Evaluating the Effectiveness of Primary Versus Secondary Seizure Prophylaxis in Stroke Patients at High-Risk for Post-stroke Epilepsy: A Systematic Review

Background: Post-stroke epilepsy (PSE) is a common complication of acute ischemic stroke (AIS) that can increase disability, cognitive impairment, and mortality. Current guidelines do not routinely recommend prophylactic anti-seizure medications (ASMs), but their use in high-risk patients, as identified by the SELECT score, could potentially prevent neuronal injury and reduce mortality and readmissions. This review summarizes evidence comparing primary and secondary prophylaxis strategies in AIS. Methods: A systematic search was conducted in PubMed, Embase, Cochrane and Web of Science using predefined search criteria for relevant literature from inception to July 2025. Two authors independently performed a database search, data collection, and study quality evaluation. The primary outcome was PSE. Results: This review included data from 6 studies evaluating more than 5000 stroke patients. In patients who received a short-term prophylactic course of diazepam after AIS, seizures occurred less frequently in the diazepam group compared to placebo, but the difference was not statistically significant (1.5% vs 3.3%, IRR 0.45, 95% CI 0.18–1.16, p=0.11). Interestingly, in the subgroup analysis of patients with cortical anterior circulation stroke, the seizure rate was significantly lower in the diazepam group compared to placebo (0.9% vs. 4.6%, IRR 0.2, 95% CI 0.05–0.78, p=0.02). In patients aged 65 or older with new, non-severe AIS, primary prophylaxis with an ASM increased mortality even after adjusting for confounding factors (Risk difference 131 deaths/1000 patients, 95% CI 65–200). A decision analysis model evaluating primary and secondary ASM prophylaxis strategies on quality-adjusted life-years (QALYs) in patients with AIS revealed that primary prophylaxis resulted in fewer QALYs than secondary prophylaxis, which was safer and more effective. Starting ASMs promptly after PSE is identified, but continuing them only for a limited time, led to better patient outcomes than indefinite treatment. Conclusion: Overall, secondary prophylaxis was safer and more effective than primary prophylaxis. However, there is limited data to suggest that some patients, who are deemed high-risk for developing PSE, may benefit from early ASM use. Since there are no direct comparisons of ASM prophylaxis strategies in this patient population, we hope this study will serve as a platform for larger multicenter studies, which could focus on targeted interventions for this high-risk group.