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Introduction: Previous animal studies suggest that post-stroke epileptogenesis is facilitated by activation of albumin-mediated TGF-β signaling and that blockade of this pathway with the angiotensin II receptor blocker (ARB) losartan prevents the development of recurrent spontaneous seizures in rat models. We used a large national retrospective cohort to examine the association between post-stroke seizures and ARB exposure among Veterans with ischemic stroke.Hypothesis: ARB exposure is negatively associated with post-stroke seizures.Methods: We reviewed data from the Veteran’s Affairs Office of Quality and Performance retrospective cohort stroke study, which included Veterans discharged from a VA hospital in 2007 with a primary diagnosis of ischemic stroke. Clinical and demographic data were abstracted by chart review, including NIHSS score. Abstracted data were linked to ICD9 codes for seizure and epilepsy 2 years before and 3 years after stroke admission and to pharmacy data. Patients with seizures prior to stroke admission were excluded. Patients were considered to have ARB exposure if they had a prescription for an ARB at any time during the data collection period. The association between clinical, demographic, and ARB exposure and post-stroke seizures was examined using univariate and multivariate logistic regression analysis.Results: Of 3299 eligible patients, 453 (13.7%) were prescribed ARB therapy and 307 (9.3%) had a diagnosis of seizure or epilepsy. In univariate analysis, age, NIHSS, history of ischemic stroke, seizure at onset of stroke, and history of head trauma within 3 months were independently associated (p≤0.10) with post-stroke seizures. In multivariate analysis, only age (OR 1.026; 95% CI 1.014-1.038), NIHSS (0.973; 0.953-0.993), history of ischemic stroke (0.603; 0.460-0.789), and seizure at onset (0.033; 0.014-0.079) were independently associated (p≤0.05) with post-stroke seizures.Conclusion: In this retrospective post-stroke cohort, ARB exposure was not associated with a reduction in post-stroke seizures. Further, prospective studies assessing the development of post-stroke seizures and the use of ARBs over time are required.