Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials
Secades JJ (1), Alvarez-Sabín J (2), Castillo J (3), Díez-Tejedor E (4), Martínez-Vila E (5), Ríos J (6), Oudovenko N (7).
(1) Scientific Department, Ferrer Group, Barcelona, Spain.
(2) Department of Neurology, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
(3) Department of Neurology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
(4) Department of Neurology and Stroke Centre, Hospital Universitario La Paz, Madrid, Spain.
(5) Department of Neurology, Clínica Universitaria de Navarra, Pamplona, Spain.
(6) Biostatistics and Data Management Core Facility, IDIBAPS (Hospital Clinic), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
(7) Scientific Department, Ferrer Group, Barcelona, Spain.
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.
A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke.
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).
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.
CITATION J Stroke Cerebrovasc Dis. 2016 May 24. pii: S1052-3057(16)30019-2. doi: 10.1016/j.jstrokecerebrovasdis.2016.04.010