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Choice of Epilepsy Anti-Seizure Medications and Associated Outcomes in Medicare Beneficiaries

Brooks, J. D.; Caze de Medeiros, R.; Sun, S.; Sankaranarayanan, M.; Westover, M. B.; Schwamm, L. H.; Newhouse, J. P.; Haneuse, S.; Moura, L. M. V. R.

2025-03-20 neurology
10.1101/2025.03.18.25324227 medRxiv
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BackgroundThe lack of specific guidelines for seizure treatment after acute ischemic stroke (AIS), makes the choice of an appropriate anti-seizure medication choice a challenge for providers because each drug may have different adverse effects and outcomes. MethodsIn this retrospective matched cohort study, we analyzed a 20% sample of U.S. Medicare beneficiaries aged 65 and over hospitalized for a first acute ischemic stroke (AIS) between 2009-2021 who were discharged home. We included individuals who were enrolled in Medicare hospital, medical and prescription drug insurance for 12 months prior to hospitalization and were not taking epilepsy-specific anti-seizure medication (ESM) prior to hospitalization. We matched individuals on days from discharge to ESM initiation. Individuals who initiated ESMs other than Levetiracetam, i.e. Lamotrigine, Carbamazepine, Oxcarbazepine within 30 days of discharge (N = 229) were matched to Levetiracetam initiators (N =687). We investigated the time to seizure-like events, emergency department (ED) visits, and re-hospitalizations with a follow-up of 180 days after initiation using a semi-competing risk framework. We estimated the average treatment effect among the treated i.e. those who received other ESMs. ResultsThe matched cohort of 916 ESM initiators had a median age of 74 (IQR 69, 82) and was 57% female and 71% Non-Hispanic White. Using the semi-competing risk framework, those who received other ESM had a 37% lower hazard of seizure-like events compared to receiving LEV, given that death had not occurred, hazard ratio 0.63 (95% CI: 0.43, 0.91). Among those who initiated ESMs other than Levetiracetam, the hazard of ED visits and hospitalizations, given that death had not occurred, did not different significantly from initiating Levetiracetam; hazard ratios 1.00 (95% CI: 0.80, 1.25) and 0.98 (95% CI: 0.75, 1.28), respectively. ConclusionIn a sample of Medicare beneficiaries hospitalized for acute ischemic stroke and discharged home, initiating Levetiracetam in the outpatient setting was associated with a higher risk of seizure-like events compared to other ESMs. However, no significant differences were observed in the incidence of ED visits or hospitalizations, suggesting comparable safety profiles in these broader clinical outcomes.

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