Citicoline Should Not Be Initiated for Acute Ischemic Stroke
The American Heart Association/American Stroke Association issues a Grade A (strong) recommendation against the use of citicoline for patients with acute ischemic stroke, and it should not be started at any time point after cerebral infarction. 1, 2
Guideline-Based Recommendation
No neuroprotective agent, including citicoline, can be recommended for the treatment of acute ischemic stroke based on the highest quality evidence from the American Heart Association/American Stroke Association guidelines. 1, 3, 2
The International Citicoline Trial on Acute Stroke (ICTUS), which enrolled 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
This large, well-designed European multicenter randomized trial provides the most recent and highest quality evidence that definitively contradicts earlier, smaller studies. 1
Why Earlier Studies Are Not Applicable
While a patient-level pooled analysis of four smaller US trials suggested benefit when citicoline was started within 24 hours (25.2% recovery vs 20.2% placebo), this finding was not confirmed by the subsequent definitive ICTUS trial. 1, 4
The pooled analysis and observational studies from Korea and Russia showing positive effects 5, 6, 4 are superseded by the larger, more rigorous ICTUS trial that specifically tested this hypothesis and found no benefit. 1, 2
A 2016 meta-analysis attempted to explain away negative results by suggesting dilution of effect in rtPA-treated patients, but this post-hoc subgroup analysis does not override the primary negative findings of the definitive trial. 7
What Should Be Done Instead
Focus clinical resources on proven acute stroke interventions rather than citicoline:
Intravenous alteplase (rtPA) within 3-4.5 hours of symptom onset for eligible patients. 3, 2
Endovascular thrombectomy within appropriate time windows for large vessel occlusions. 3, 2
Early aspirin therapy (160-325 mg) within 24-48 hours for patients not receiving thrombolysis, after excluding intracranial hemorrhage. 8, 3, 2
Admission to a specialized stroke unit for coordinated interdisciplinary care. 8, 1
Blood pressure management: maintain <180/105 mmHg for 24 hours after reperfusion therapy. 8, 3
Clinical Pitfall to Avoid
Do not be swayed by older positive studies or meta-analyses when a large, definitive, more recent randomized controlled trial contradicts them. The ICTUS trial (2,298 patients) specifically tested the hypothesis generated by earlier pooled analyses and found no benefit, making citicoline an ineffective intervention that diverts attention from proven therapies. 1, 2