Abstract A143: Clinical effectiveness and Safety of Glibenclamide in Post-Stroke Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Stroke is a leading cause of death and disability worldwide. Among its complications, secondary cerebral edema is determinant in prognosis and potentially treatable in the acute phase. Glibenclamide, a sulfonylurea, has emerged as a potential therapeutic in brain swelling by blocking the SUR1-TRPM4 channel, involved in edema formation. However, evidence concerning its effectiveness in improving neurological outcomes post-stroke and clinical safety remains unclear. This systematic review and meta-analysis evaluated the efficacy and safety of glibenclamide in the post-stroke patients. Methods: The protocol was registered in PROSPERO (CRD420251001371). Pubmed, Embase, and Cochrane databases considering only randomized controlled trials (RCTs) comparing intravenous or oral glibenclamide to placebo in post-stroke patients. The primary endpoint evaluated functional outcomes through the Modified Rankin Score (mRs) scale 0-2 (favorable) and 3-5 (unfavorable) after ≥ 90 days. Secondary outcomes included decompressive craniectomy, mortality and clinical hypoglycemia. Data pooled analysis was performed using random-effects models and heterogeneity was assessed with I 2 statistics. The certainty of evidence was assessed by GRADE method. Results: A total of 1,270 patients from eight RCTs were included, of whom 780 had ischemic stroke and 490 had hemorrhagic stroke. The mean NIHSS score was 13. Most participants were male (61%), with a mean age of 57.9. Treatment with glibenclamide showed no significant difference compared to placebo in the distribution of mRS scores 0–2 (RR: 1.07; 95% CI: 0.98 to 1.17) and 3–5 (RR: 0.96; 95% CI: 0.80 to 1.41). There was no statistically significant difference in decompressive craniectomy rates (RR: 1.05, 95% CI: 0.80 to 1.37) or mortality (RR: 1.03, 95% CI: 0.78 to 1.35) between the intervention and placebo groups. For these outcomes, the certainty of evidence was rated as high. In contrast, treatment with glibenclamide was associated with a significantly higher incidence of hypoglycemia, although the certainty of evidence was rated low due inconsistency and imprecision (RR: 3.57, 95%CI: 1.19 to 10.68). Conclusions: In conclusion, this meta-analysis found no significant benefit of glibenclamide in acute stroke, with no improvement in functional outcomes, reduction in the need for decompressive craniectomy, or increase in survival. Hypoglycemia was more frequently observed in patients using glibenclamide.