Effectiveness and Safety of Early Treatment with Sulfonylureas in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis
Jimena Gonzalez Salido1, Luis A. Marin-Castañeda2, Dante A. Ayala-Ortiz3, Luis Cueva-Cañola4, Francisco de Jesús García-Mendoza5, Iris E. Martínez-Juárez1, Gerson Ángel Alavez6, Geronimo Pacheco Aispuro6
1Epilepsy Clinic, Epilepsy Clinic & Clinical Epileptology Fellowship, National Institute of Neurology and Neurosurgery “Manuel Velasco Suarez” (NINNMVS) & Faculty of Medicine, UNAM, Mexico City and Clinical Epileptology Fellowship NINNMVS/UNAM, 2Department of Neurophysiology, National Institute of Neurology and Neurosurgery. Mexico City, Mexico., 3Faculty of Medicine, Universidad del Valle de México, Zapopan, México., 4Faculty of Medicine, Universidad Nacional de Piura, Peru., 5Faculty of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, México, 6Neurology Department, Hospital Ángeles del Pedregal. Mexico City, Mexico.
Objective:
This systematic review and meta-analysis aims to assess the effectiveness of treatment with sulfonylureas in patients with aneurysmal subarachnoid hemorrhage (aSAH).
Background:
Sulfonylureas have been shown to prevent neuroinflammation and cerebral edema and improve neurological outcomes by modulating the sulfonylurea receptor 1(SUR1) protein. This protein regulates the transient receptor potential melastatin 4 (TRPM4) cation channel, which is notably upregulated in aneurysmal subarachnoid hemorrhage (aSAH) and plays a significant role in acute brain injury.
Design/Methods:
Following PRISMA guidelines, a systematic search of PubMed, Embase, and Cochrane databases was conducted from inception through October 2024. Randomized controlled trials reporting functional outcomes and complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) were included. The quality of the studies was assessed using the RoB2 tool, and data were analyzed with a random-effects model.
Results:
From an initial pool of 874 articles, 5 studies met the inclusion criteria. Due to high heterogeneity in reported outcomes, we were only able to analyze favorable modified Rankin Scale (mRS) scores (>3) at discharge and at 6 months. No statistically significant differences were found between groups at discharge (OR 0.86 [0.46, 1.60], p=0.63) or at 6 months of follow-up (OR 1.38 [0.78, 2.44], p=0.28). Our analysis showed low to moderate heterogeneity (0%, p=0.38 at discharge; 35%, p=0.19 at 6 months). However, there was a trend toward favorable outcomes in the placebo group. Adverse events were poorly reported, with hypoglycemia, cerebral infarction, and hydrocephalus being the most commonly mentioned complications.
Conclusions:
This meta-analysis underscores the need for future studies with larger populations to better assess the potential role of sulfonylureas in improving outcomes in patients with aSAH. Currently, the available literature suggests a trend toward no significant effect of sulfonylurea use on patient outcomes.
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