Citicoline for Acute Ischemic Stroke
Citicoline is not recommended for the treatment of acute ischemic stroke based on high-quality evidence from multiple randomized controlled trials, including the definitive ICTUS trial, which showed no benefit in improving 90-day outcomes. 1, 2
Guideline Position
The American Heart Association/American Stroke Association explicitly states that citicoline cannot be recommended for acute ischemic stroke treatment (Grade A recommendation). 1, 2 This recommendation is based on:
The International Citicoline Trial on Acute Stroke (ICTUS), the largest and most definitive trial with 2,298 patients with moderate to severe ischemic stroke, found no difference in 90-day global outcomes between citicoline and placebo (OR 1.03,95% CI 0.86-1.25, p=0.364). 1, 2
Multiple earlier clinical trials testing citicoline as a neuroprotective agent produced disappointing or negative results, with some showing worse outcomes in treated patients. 3
The 2013 AHA/ASA guidelines note that although a preliminary study suggested benefit, a subsequent large trial was negative. 3
Conflicting Evidence to Consider
While guidelines are clear against citicoline use, some post-hoc and pooled analyses suggest potential benefit in specific subgroups:
A patient-level pooled analysis of four trials (1,372 patients) showed 25.2% recovery in citicoline-treated patients versus 20.2% in placebo (OR 1.33,95% CI 1.10-1.62, p=0.0034) when started within 24 hours. 4
A 2016 meta-analysis found benefit in patients not treated with rtPA (OR 1.63,95% CI 1.18-2.24), suggesting the effect may be diluted when combined with thrombolysis. 5
A Korean surveillance study of 4,191 patients showed improvements in functional outcomes, particularly with doses ≥2000 mg/day. 6
However, these post-hoc findings do not override the negative results from the prospectively designed, adequately powered ICTUS trial, which represents the highest quality evidence. 1
What to Use Instead
Focus on proven interventions with established mortality and morbidity benefits:
IV rtPA within 3-4.5 hours of symptom onset for eligible patients (Grade 1A for <3 hours, Grade 2C for 3-4.5 hours). 2
Endovascular thrombectomy for large vessel occlusions within appropriate time windows. 2
Aspirin 160-325 mg within 24-48 hours for patients not receiving thrombolysis. 3, 2
Admission to specialized stroke units with coordinated interdisciplinary care. 2
Blood pressure management and control of physiological parameters. 1, 2
Clinical Pitfall
Do not delay proven therapies (imaging, rtPA evaluation, thrombectomy assessment) to administer unproven neuroprotective agents like citicoline. 2 Time is brain—every minute counts for interventions with demonstrated efficacy.