Introduction: Stroke is the third leading condition with the highest mortality and death and is a major cause of disability. The estimated number of deaths due to stroke is about 5.71 million people as per the WHO data, and is estimated to peak at 7.8 million in 2030. Citicoline is believed to exert neuroprotection and neurorestoration intracellularly by supporting cellular phospholipid synthesis. Citicoline is used in Acute Ischemic Stroke patients, however, there is not enough statistical evidence available for the benefits of the same. Hence, this calls for a meta-analysis of RCTs on a larger scale to generate highest level of scientific evidence regarding the controversial negative studies of Citicoline when tested against placebo.

Objectives: To review and analyze statistical evidence from existing randomized controlled trials, the therapeutic efficacy of Citicoline in acute ischemic stroke (AIS) patients.

Materials & Methods: A total of 17 studies, involving 5127 patients were included. The studies were double-blind, randomized, and placebo-controlled clinical trials studying the effect of Citicoline on patients with Acute Ischemic Stroke. The included patients suffered from an Acute Ischemic Stroke with a minimum therapeutic window of 6 hours. The treatments tested were either Citicoline, with doses ranging from 250 to 4000 mg daily, or placebo. The duration of the treatment ranged from 10 days to 9 weeks. The principal summary measures were the Odd’s Ratio(OR) and Relative Risk (RR). For the measurement of treatment effect Rev Man 5.4.1 version software by Cochrane Database will be utilized to calculate Odd’s ratio and Relative Risk(RR).

Results: The RR(for 5127 participants) was 1.301(random effect model) and 1.163(fixed effect model)[95% confidence interval (CI) 1.081 to 1.2521 (fixed effect model), p<0.001] and the overall OR(for 5127 participants) was 1.769(random effect model) and 1.281(fixed effect model)[95% confidence interval (CI) 1.137 to 1.443 (fixed effect model), p<0.001], indicating a slight advantage of Citicoline over placebo treatment. Citicoline was also found to be associated with a less number of adverse events and deaths compared to placebo.

Conclusion: Citicoline is proven to be slightly more efficacious than placebo, with lesser adverse events and deaths. However the margin of benefit is narrow. Future trials comparing the same, on higher number of patients is necessary to draw a final conclusion on it.