Uric acid improves glucose-driven oxidative stress in human ischemic stroke

© 2015 American Neurological Association. Objective A study was undertaken to test in a subgroup reanalysis of the URICO-ICTUS trial whether uric acid is superior to placebo in improving the functional outcome in patients with acute stroke and hyperglycemia. Methods Patients were part of the URICO-ICTUS trial, a double-blind study that compared the administration of uric acid versus placebo in stroke patients treated with alteplase within 4.5 hours of onset. The effect of therapy on the rate of excellent outcome at 90 days (modified Rankin Scale ¿ 2) in each tertile of admission glucose was assessed with multivariate adjusted models in 409 of the 421 randomized patients who had available pretreatment glucose levels. The effect of therapy on infarct growth was assessed in 72 patients who had longitudinal multimodal brain imaging. Results Uric acid was associated with an increased rate of excellent outcome in patients with glucose levels in the upper tertile range (odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.0-8.3). However, the effect was not apparent for patients in the middle tertile (OR = 1.6, 95% CI = 0.8-3.6) or lower tertile of glucose (OR = 1.1, 95% CI = 0.5-2.6). Uric acid therapy was more effective than placebo in limiting infarct growth in the upper tertile range (Mann-Whitney U test, p = 0.04) but not in the middle tertile (p = 0.95) or lower tertile of glucose (p = 0.30). Uric acid also proved superior to placebo in reducing infarct growth in patients with early recanalization. Interpretation Uric acid therapy was associated with reduced infarct growth and improved outcome in patients with hyperglycemia during acute stroke. Ann Neurol 2015;77:775-783The URICO-ICTUS trial was funded by the Institute of Health Carlos III of the Spanish Ministry of Health (grant number EC07/90276), by the Spanish Ministry of Economy and Competence (RETICS-INVICTUS R012/0014), and by a private grant from Fundación Doctor Melchor Colet. The medication in the study was supplied by Grifols, Barcelona, Spain. This study was also supported by the Spanish Ministry of Economy and Competitiveness (grant PI13/01268, S.A.; funded as part of the Plan Nacional R+D+ I and cofinanced by ISCIII Subdirección General de Evaluación and by the Fondo Europeo de Desarrollo Regional)Peer Reviewe