Recovering from Ischemic Stroke
Oral citicoline ups odds of favorable outcome by 33% after 12 weeks of treatment, meta-analysis shows
As the number of patients who succumb to debilitating or even fatal stroke continues to rise all over the world, medical practitioners and those in the health-care industry race against time to find the perfect way to protect people from stroke. In the past few years, studies have looked into the capacity of several compounds that interfere with biochemical mechanisms in mediating ischemic brain injury. Many of them showed promise in preclinical, animal models but failed to show conclusive benefit of efficacy in more rigorous clinical trials.
A positive meta-analysis study on citicoline, a neuroprotective agent, now provides a glimmer of hope.
A group of doctors led by Dr. Antoni Davalos of the Hospital Universitari Doctor Josep Tructa in Spain conducted an individualized pooling data meta-analysis of all prospective, randomized, placebo-controlled, double-blind clinical trials involving the use of citicoline in the management of acute ischemic stroke. The study, presented at the 2001 annual meeting of the American Neurological Association and published in late 2002 in Stroke (a journal of the American Heart Association), pointed out that citicoline is the "only putative neuroprotectant that has shown partial positive result" in all randomized, double-blind individual trials. In addition, it is the only neuroprotective agent that has shown "efficacy in the predefined primary end point of a meta-analysis."
Recovery
The primary end goal was to assess the effect of citicoline on the recovery of moderate to severe acute ischemic stroke patients after three months. Efficacy was assessed using the global estimation effect (Odds Ratio) on NIHSS, mRS, and Barthel Index. Secondarily, the study looked at the efficacy of the drug in individual scales. Lastly, the issue was assessed using reports of adverse events in each trial.
Four clinical trials satisfied the predetermined requirements (must be placebo-controlled, randomized trial with more than 10 patients in each treatment group; identical end points obtained using mRS, Barthel Index, and National Institutes of Health Stroke Scale; six weeks of treatment; and must use good clinical practice. The patients were divided into four groups (placebo, 500mg, 1000mg, and 2000mg citicoline) with 1,372 patients fulfilling the inclusion criteria (placebo=583; citicoline=789).
The authors said "citicoline was associated with significantly greater recovery" by the third month. For the primary objective, citicoline increased the odds of favorable outcome or recovery by 33 percent (95 percent CI, p=0.0034). The most favorable dose was 2000mg having increased odds of recovery by 38 percent.
Individual scales produced similar results with citicoline increasing the probability of complete recovery of activities of daily living (Barthel Index) by 29 percent, complete functional recovery by 42 percent, and complete neurological recovery (NIHSS) by 28 percent.
Citicoline had no effect on mortality after three months (citicoline=18.8 percent; placebo=17.8 percent). There was little difference between the two groups in terms of overall adverse events. A significant difference was found specific adverse events: anxiety (citicoline=13.7 percent, placebo=9.8), depression (citicoline=22.5 percent, placebo=27.4), and urinary incontinence (citicoline=10.5 percent, placebo=14).
In contrast with other drugs studied for stroke, which have failed in the first six hours of stroke, citicoline has shown improvement within the first 24 hours, a longer therapeutic window, the authors observed. It did not cause adverse events that led to the failure of other drugs, providing for a favorable risk-to-benefit ratio for stroke patients, they added.
The study concluded that treatment with oral citicoline within the first 24 hours after symptom onset in patients with moderate to severe stroke increases the probability of complete recovery in three months.
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