Abstract

Introduction: Sulfonylurea medications may reduce cerebral edema following ischemic stroke. Prior retrospective studies evaluated the impact of pre-stroke sulfonylurea exposure on outcome metrics yielding inconclusive results and have not provided results based on stroke subtype. We hypothesize that exposure to pre-stroke sulfonylureas would have a better outcome than unexposed regardless of stroke etiology. Methods: We performed a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) dataset. Only those with pre-enrollment diabetes mellitus were included. The primary exposure was pre-stroke sulfonylurea usage. The primary outcome was 90-day functional outcome by mRS 0 - 2 (good) versus 3 - 6 (poor). Ischemic stroke was categorized as lacunar or non-lacunar. Standard descriptive and logistic regression analyses were used for data interpretation. Results: A total of 919 individuals met inclusion criteria: mean age 65 years, 58% male, 256 (28%) being sulfonylurea exposed. Lacunar stroke was diagnosed in 220 (24%) of the cohort. Pre-stroke sulfonylurea exposure was reported in 256 participants (lacunar: 59 vs. non-lacunar: 197, p = 0.69). Amongst the whole cohort, exposed individuals were more likely to have a poor outcome (OR 1.7, 95%CI 1.25 - 2.32, p = <0.001). The association between sulfonylurea exposure and poor outcome remains in those with non-lacunar stroke (OR 1.67, 95%CI 1.19 - 2.32, p = 0.003) as opposed to lacunar stroke (OR 0.60, 95%CI 0.43 - 0.84, p = 0.003) (pinteraction 0.1). Conclusion: Patients with pre-stroke sulfonylurea exposure were more likely to have a poor outcome at 90 days. Current trials investigating sulfonylurea infusion for cerebral edema, though these data suggest chronic oral administration may mitigate this response. Limitations exist including potential unaccounted differences amongst the cohort. This is a hypothesis generating study with future studies needed expand and corroborate our findings.

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