Why Citicoline (A Medical Food) Should Not Be Prescribed to Treat People with Acute Ischemic Stroke: The Certainty of the Evidence

Abstract

Background: Citicoline, a medical food prescribed for ischemic stroke, faces scrutiny due to its unproven efficacy and potential harms. This essay, drawing on a recent Cochrane review and focusing solely on all-cause mortality, advocates for a critical reevaluation of its use. Rather than offering an updated Cochrane review, this analysis provides a reflective perspective through the lens of Evidence-based Medicine and Philosophy of Science.

Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.?

 Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties.

Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials.

Data collection and analysis: I identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. I estimated risk ratios (RRs) for that outcome. I measured statistical heterogeneity using the I² statistic. I conducted the analyses using the fixed effect model. I did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. I used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. I used a Trial Sequential Analysis with Copenhagen Trial Unit Software. I estimated a Bayes factor from the relative risk and 95% confidence interval.

Results: I identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. I conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I² = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline.

Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.