Citicoline in Acute Ischemic Stroke
Citicoline is not recommended for the treatment of acute ischemic stroke, as it has failed to demonstrate consistent efficacy in improving clinical outcomes despite multiple large-scale randomized controlled trials. 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 based on multiple randomized controlled trials). 1, 2 This represents the highest level of evidence against its use in clinical practice.
Key Evidence Against Citicoline
The International Citicoline Trial on Acute Stroke (ICTUS), the definitive large-scale trial, found no benefit:
- This European multicenter trial enrolled 2,298 patients with moderate to severe ischemic stroke 1
- The 90-day global outcome showed no difference between citicoline and placebo (OR 1.03,95% CI 0.86-1.25, p=0.364) 1
- This high-quality evidence definitively refutes earlier suggestions of benefit 1
Earlier trials also failed to demonstrate efficacy on primary endpoints:
- A 1999 trial of 394 patients using 500 mg daily failed its primary analysis and showed no difference in Barthel Index ≥95 at 12 weeks (placebo 40%, citicoline 40%) 3
- A 2001 trial of 899 patients using 2000 mg daily showed no difference in the primary endpoint of ≥7-point NIHSS improvement at 90 days (placebo 51%, citicoline 52%) 4
Why Post-Hoc Analyses Should Not Change Practice
While a pooled analysis suggested 25.2% recovery in citicoline-treated patients versus 20.2% in placebo (OR 1.33,95% CI 1.10-1.62) 5, this finding is contradicted by the later, larger, and more definitive ICTUS trial. 1 Post-hoc analyses from earlier trials showing possible benefit with modified Rankin 0-1 outcomes 4 are hypothesis-generating only and were not confirmed in prospective testing.
What You Should Do Instead
Focus on evidence-based acute stroke interventions:
- Immediate IV alteplase (rtPA) within 3-4.5 hours of symptom onset after excluding hemorrhage on CT/MRI 6, 2
- Endovascular thrombectomy for large vessel occlusions within appropriate time windows 2
- Aspirin 160-325 mg within 24-48 hours after excluding hemorrhage, for patients not receiving thrombolysis 6, 2
- Blood pressure management: Lower to <185/110 mmHg before thrombolysis and maintain <180/105 mmHg for 24 hours afterward 6, 2
Critical supportive care measures:
- Maintain oxygen saturation >94% 6
- Treat hyperthermia (temperature >38°C) with antipyretics 6
- Use isotonic fluids (0.9% saline) rather than hypotonic solutions to avoid worsening cerebral edema 6
- Maintain blood glucose 140-180 mg/dL; urgently correct hypoglycemia <60 mg/dL 6
- Cardiac monitoring for at least 24 hours to detect arrhythmias 6
Clinical Pitfall
Do not delay proven therapies while considering unproven neuroprotective agents. Time is critical in acute stroke management—every minute counts for thrombolysis and thrombectomy eligibility. 2