Glibenclamide in aneurysmal subarachnoid hemorrhage: a randomized controlled clinical trial
Bruno Braga Sisnando da Costa, Isabela Costola Windlin, Edwin Koterba, Vitor Nagai Yamaki, Nícollas Nunes Rabelo, Davi Jorge Fontoura Solla, Antonio Carlos Samaia da Silva Coelho, João Paulo Mota Telles, Manoel Jacobsen Teixeira, Eberval Gadelha Figueiredo
Abstract
OBJECTIVE: Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide's impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS). RESULTS: A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2-4), 3 (IQR 3-4), and 3 (IQR 1-4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29-1.48], adjusted common OR 1.25 [95% CI 0.46-3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0-2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%). CONCLUSIONS: In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.