Citicoline Should Not Be Used for Acute Ischemic Stroke
The American Heart Association/American Stroke Association explicitly states that citicoline cannot be recommended for the treatment of acute ischemic stroke (Grade A recommendation), as multiple high-quality randomized controlled trials have failed to demonstrate consistent efficacy in improving patient outcomes. 1, 2
Definitive Evidence Against Citicoline
The strongest evidence comes from the International Citicoline Trial on Acute Stroke (ICTUS), which enrolled 2,298 patients with moderate to severe ischemic stroke and 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 This large, well-designed European multicenter trial provides high-quality evidence that citicoline does not improve meaningful clinical outcomes. 1
Why Earlier Studies Were Misleading
A 2001 phase III trial of 899 patients showed no benefit on the primary planned analysis (51% vs 52% achieving ≥7-point NIHSS improvement), though post-hoc analyses suggested possible modest effects using different outcome measures. 3 Post-hoc analyses are hypothesis-generating only and cannot override negative primary endpoints. 3
A 2016 meta-analysis suggested benefit (OR 1.56,95% CI 1.12-2.16), but this finding is undermined by the subsequent large ICTUS trial and represents the problem of combining smaller, potentially biased studies. 4 The meta-analysis authors themselves noted that when citicoline was added to rtPA (the current standard of care), the benefit was diluted or absent. 4
Observational studies from Korea and other regions showing benefit 5 lack the rigor of placebo-controlled trials and are subject to selection bias and confounding.
What You Should Do Instead
Focus on proven, time-sensitive interventions for acute ischemic stroke:
Immediate brain imaging with non-contrast CT or MRI to determine stroke type and treatment eligibility. 2
IV recombinant tissue plasminogen activator (rtPA) within 3 hours (Grade 1A) or 4.5 hours (Grade 2C) of symptom onset for eligible patients. 2
Endovascular thrombectomy for large vessel occlusions within appropriate time windows. 2
Early aspirin therapy (160-325 mg) within 24-48 hours for patients not receiving thrombolysis, after excluding intracranial hemorrhage. 1, 2
Blood pressure management: Lower to <185/110 mmHg before reperfusion therapy and maintain <180/105 mmHg for 24 hours afterward. 2 For patients not receiving reperfusion, only lower BP if extremely elevated (>220/120 mmHg). 2
Critical Pitfall to Avoid
Do not waste time or resources on unproven neuroprotective agents like citicoline when the focus should be on rapid assessment and administration of proven therapies where time is brain. 2 The therapeutic window for effective interventions like rtPA and thrombectomy is narrow, and delays reduce efficacy dramatically. 2
Application to Hemorrhagic Stroke
The AHA/ASA recommendation against citicoline extends to hemorrhagic stroke given the complete absence of definitive evidence, despite preliminary underpowered pilot studies. 6 For hemorrhagic stroke, prioritize acute blood pressure management, anticoagulation reversal when applicable, and surgical evaluation for cerebellar hemorrhages. 6