title: Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.
abstract: BACKGROUND
  Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo.
  
  
  METHODS
  A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke.
  
  
  RESULTS
  Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53).
  
  
  CONCLUSIONS
  This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit.
authors.affiliation: Scientific Department, Ferrer Group, Barcelona, Spain. Electronic address: jsecades@ferrer.com.
authors.forename: Julio J
authors.initials: JJ
authors.lastname: Secades
authors.affiliation: Department of Neurology, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.affiliation: Department of Neurology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Castillo
authors.affiliation: Department of Neurology and Stroke Centre, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Exuperio
authors.initials: E
authors.lastname: Díez-Tejedor
authors.affiliation: Department of Neurology, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Vila
authors.affiliation: Biostatistics and Data Management Core Facility, IDIBAPS (Hospital Clinic), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ríos
authors.affiliation: Scientific Department, Ferrer Group, Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Oudovenko
mesh_terms: D002545:Brain Ischemia / Q000150:complications; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology
chemical_list: D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline
keywords: Acute ischemic stroke; CDP-choline; citicoline; meta-analysis; neuroprotection; pharmacological treatment; systematic review; therapy