Laura Llull1, Carlos Laredo1, Arturo Renú1, Belén Pérez1, Elisabet Vila1, Víctor Obach1, Xabier Urra1, Anna Planas1, Sergio Amaro1, Ángel Chamorro2. 1. From the Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, August Pi i Sunyer Biomedical Research Institute (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain (L.L., C.L., A.R., V.O., X.U., S.A., Á.C.); Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain (B.P., E.V.); Department of Brain Ischemia and Neurodegeneration, Institute for Biomedical Research of Barcelona, Spanish Research Council, Barcelona, Spain (A.P.); and Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain (A.P.). 2. From the Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, August Pi i Sunyer Biomedical Research Institute (Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer), Barcelona, Spain (L.L., C.L., A.R., V.O., X.U., S.A., Á.C.); Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain (B.P., E.V.); Department of Brain Ischemia and Neurodegeneration, Institute for Biomedical Research of Barcelona, Spanish Research Council, Barcelona, Spain (A.P.); and Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain (A.P.). achamorro@clinic.ub.es.
Abstract
BACKGROUND AND PURPOSE: It is unknown whether women and men with acute ischemic stroke respond similar to an antioxidant regimen administered in combination with thrombolysis. Here, we investigated the independent effect of sex on the response to uric acid (UA) therapy in patients with acute stroke treated with alteplase. METHODS: In the Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial, 206 women and 205 men were randomized to UA 1000 mg or placebo. In this reanalysis of the trial, the primary outcome was the rate of excellent outcome at 90 days (modified Rankin Scale, 0-1, or 2, if premorbid score of 2) in women and men using regression models adjusted for confounders associated with sex. The interaction of UA levels by treatment on infarct growth was assessed in selected patients. RESULTS: Excellent outcome occurred in 47 of 111 (42%) women treated with UA, and 28 of 95 (29%) treated with placebo, and in 36 of 100 (36%) men treated with UA and 38 of 105 (34%) treated with placebo. Treatment and sex interacted significantly with excellent outcome (P=0.045). Thus, UA therapy doubled the effect of placebo to attain an excellent outcome in women (odd ratio [95% confidence interval], 2.088 [1.050-4.150]; P=0.036), but not in men (odd ratio [95% confidence interval], 0.999 [0.516-1.934]; P=0.997). The interactions between treatment and serum UA levels (P<0.001) or allantoin/UA ratio (P<0.001) on infarct growth were significant only in women. CONCLUSIONS: In women with acute ischemic stroke treated withalteplase, the administration of UA reduced infarct growth in selected patients and was better than placebo to reach excellent outcome. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00860366.
RCT Entities:
BACKGROUND AND PURPOSE: It is unknown whether women and men with acute ischemic stroke respond similar to an antioxidant regimen administered in combination with thrombolysis. Here, we investigated the independent effect of sex on the response to uric acid (UA) therapy in patients with acute stroke treated with alteplase. METHODS: In the Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial, 206 women and 205 men were randomized to UA 1000 mg or placebo. In this reanalysis of the trial, the primary outcome was the rate of excellent outcome at 90 days (modified Rankin Scale, 0-1, or 2, if premorbid score of 2) in women and men using regression models adjusted for confounders associated with sex. The interaction of UA levels by treatment on infarct growth was assessed in selected patients. RESULTS: Excellent outcome occurred in 47 of 111 (42%) women treated with UA, and 28 of 95 (29%) treated with placebo, and in 36 of 100 (36%) men treated with UA and 38 of 105 (34%) treated with placebo. Treatment and sex interacted significantly with excellent outcome (P=0.045). Thus, UA therapy doubled the effect of placebo to attain an excellent outcome in women (odd ratio [95% confidence interval], 2.088 [1.050-4.150]; P=0.036), but not in men (odd ratio [95% confidence interval], 0.999 [0.516-1.934]; P=0.997). The interactions between treatment and serum UA levels (P<0.001) or allantoin/UA ratio (P<0.001) on infarct growth were significant only in women. CONCLUSIONS: In women with acute ischemic stroke treated with alteplase, the administration of UA reduced infarct growth in selected patients and was better than placebo to reach excellent outcome. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00860366.
Authors: Roy G Cutler; Simonetta Camandola; Neil H Feldman; Jeong Seon Yoon; James B Haran; Sandro Arguelles; Mark P Mattson Journal: Neurobiol Aging Date: 2018-12-12 Impact factor: 4.673
Authors: Sarah R Martha; Lisa A Collier; Stephanie M Davis; Sarah J Goodwin; David Powell; Doug Lukins; Justin F Fraser; Keith R Pennypacker Journal: J Neurosci Res Date: 2019-04-03 Impact factor: 4.164
Authors: Michael A Schwarzschild; Eric A Macklin; Rachit Bakshi; Shamik Battacharyya; Robert Logan; Alberto J Espay; Albert Y Hung; Grace Bwala; Christopher G Goetz; David S Russell; John L Goudreau; Sotirios A Parashos; Marie H Saint-Hilaire; Alice Rudolph; Joshua M Hare; Gary C Curhan; Alberto Ascherio Journal: Neurology Date: 2019-09-04 Impact factor: 9.910
Authors: Lynda D Lisabeth; Jonggyu Baek; Lewis B Morgenstern; Mathew J Reeves; Devin L Brown; Darin B Zahuranec; Melinda A Smith; Brisa N Sánchez Journal: Ann Epidemiol Date: 2017-07-13 Impact factor: 3.797