title: Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  URL: https://clinicaltrials.gov. Unique identifier: NCT00860366.
authors.affiliation: 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.).
authors.forename: Laura
authors.initials: L
authors.lastname: Llull
authors.affiliation: 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.).
authors.forename: Carlos
authors.initials: C
authors.lastname: Laredo
authors.affiliation: 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.).
authors.forename: Arturo
authors.initials: A
authors.lastname: Renú
authors.affiliation: 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.).
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
authors.affiliation: 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.).
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vila
authors.affiliation: 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.).
authors.forename: Víctor
authors.initials: V
authors.lastname: Obach
authors.affiliation: 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.).
authors.forename: Xabier
authors.initials: X
authors.lastname: Urra
authors.affiliation: 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.).
authors.forename: Anna
authors.initials: A
authors.lastname: Planas
authors.affiliation: 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.).
authors.forename: Sergio
authors.initials: S
authors.lastname: Amaro
authors.affiliation: 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.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Chamorro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D014527:Uric Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D014527:Uric Acid; D010959:Tissue Plasminogen Activator
keywords: allantoin; oxidative stress; sex; stroke; uric acid