Effectiveness of Levetiracetam vs Valproic Acid for Poststroke Seizure: A Population-Based Study Using a Target Trial...

Evidence on levetiracetam for poststroke seizures is limited. Understanding whether levetiracetam effectively manages poststroke seizures is important for improving prognosis and preventing further complications in stroke patients. The aim of this study was to assess the risk of seizure rehospitalization between levetiracetam and valproic acid in patients with poststroke seizures.

Using data from Taiwan's National Health Insurance Research Database, this observational retrospective cohort study followed the target trial emulation framework to emulate a hypothetical randomized trial estimating the effect of levetiracetam for poststroke seizure management. Eligible patients were those who were hospitalized for their first seizure event (index seizure) between January 1, 2012, and December 31, 2020, and were newly prescribed levetiracetam or valproic acid monotherapy before discharge. Patients should have had a stroke-related hospitalization within 2 years before the seizure. Patients prescribed levetiracetam were assigned to the exposure group, whereas those prescribed valproic acid were assigned to the reference group, based on their first prescription after the index seizure. Inverse probability-weighted marginal structural models were used to assess outcomes between levetiracetam and valproic acid, including seizure rehospitalization as the primary outcome. Secondary outcomes included all-cause mortality and a composite of seizure rehospitalization and all-cause mortality. Both baseline and time-varying confounders were adjusted in the models.

The final sample included 740 levetiracetam users (48.5%) and 786 valproic acid users, with a mean age of 67.2 years in both groups and a similar proportion of men (59.9% for levetiracetam; 61.3% for valproic acid). In the primary outcome analysis, levetiracetam use was associated with a lower risk of seizure rehospitalization compared with valproic acid (hazard ratio 0.78; 95% CI 0.64-0.95). In secondary outcome analyses, no significant differences were observed in all-cause mortality or the composite of seizure rehospitalization and all-cause mortality.

Levetiracetam was associated with a lower risk of seizure rehospitalization, with no significant difference in the risk of all-cause mortality. These findings support levetiracetam as a potentially suitable treatment option for patients with poststroke seizures. As this study focused on monotherapy, future investigations should further explore combination antiseizure medication regimens involving levetiracetam.

This study provides Class II evidence that levetiracetam is associated with a lower risk of seizure rehospitalization compared with valproic acid in patients with post-stroke seizures.