Post-Discharge Antiseizure Medication Use and Poststroke Survival: An Emulated Target Trial in Older Adults

Purpose Levetiracetam is commonly prescribed for seizure prophylaxis after acute ischemic stroke (AIS) and often continued beyond discharge. While its short-term effectiveness for preventing poststroke seizures is established, it is unclear whether prolonged use improves survival, particularly in older adults. We estimated the effect of continued levetiracetam use on 90-day mortality among Medicare beneficiaries after AIS. Methods Using Traditional Medicare claims data (2008-2021), we identified beneficiaries aged ≥ 65 years hospitalized for AIS who initiated outpatient levetiracetam within 90 days of discharge. After 1 month of continued poststroke levetiracetam use (start of follow-up), we compared 90-day mortality between patients with a new levetiracetam dispensation within a 14-day grace period post-follow-up and those without one. We performed cloning, censoring, and weighting to address immortal-time bias and estimated standardized mortality risks, risk differences, and 95% confidence intervals (CIs). Results Among 3212 eligible beneficiaries, 1779 (55.4%) received a new levetiracetam dispensation within the 14-day grace period. After adjustment for demographics, hospitalization characteristics, timing of initiation, and comorbidities, continued use was associated with lower 90-day mortality than discontinuation (53 vs. 62 deaths per 1000; risk difference -9 per 1000; 95% CI: -12, -5). Conclusion Among older Medicare beneficiaries who initiated levetiracetam after AIS, continued outpatient use was associated with lower short-term 90-day mortality, particularly among patients aged ≥ 75 years. These findings should not be interpreted as support for routine or indefinite continuation, because the claims-based design cannot assess seizure recurrence, functional outcomes, quality of life, treatment indication, or potential neuropsychiatric harms.