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Uric acid may improve outcomes after ischemic stroke in women
The use of uric acid in women with acute ischemic stroke treated with alteplase decreases infarct growth and improves outcomes compared with placebo, according to findings from the URICO-ICTUS trial.
In the multicenter, double blind, phase 2b/3 trial, Ángel Chamorro, MD, PhD, and colleagues randomly assigned 411 patients with acute ischemic stroke (206 women) to receive an IV infusion of uric acid or placebo in addition to alteplase. The women were an average of 7 years older (median age, 79 years) than the men and had higher rates of atrial fibrillation, hypertension and other comorbidities.
Patients underwent noncontrast CT scans at baseline and at 36 hours, and were admitted into stroke units. Chamorro, director of the Comprehensive Stroke Center at the Hospital Clinic in Barcelona, Spain, and colleagues monitored participants’ vital signs and BP for at least 24 hours and evaluated neurological status according to the NIH Stroke Scale (NIHSS) every 4 to 8 hours during hospitalization. Certified stroke neurologists evaluated the functional outcome at 90 days using a modified Rankin scale. The primary outcome measure was the rate of excellent outcomes at 90 days (defined as modified Rankin scale of 0-1 in patients with a premorbid score < 2, or a score of 2 if the patient’s premorbid modified Rankin scale was 2). The researchers used regression models adjusted for sex-related confounders to evaluate this outcome in men and women. They also evaluated the interaction of uric acid levels by treatment on infarct growth in 25 women and 21 men who underwent advanced brain imaging.
Excellent outcomes were achieved in 47 of 111 women (42%) who received uric acid vs. 28 of 95 (29%) treated with placebo. In men, uric acid yielded excellent outcomes in 36 of 100 (36%) men vs. 38 of 105 (34%) treated with placebo. The researchers observed an interaction between treatment, sex and excellent outcome (P = .045), and found that uric acid therapy doubled the effect of placebo in achieving excellent outcomes in women (OR = 2.088; 95% CI, 1.05-4.15), but not men (OR = 0.999; 95% CI, 0.516-1.934).
The researchers also observed an interaction between treatment and blood uric acid levels (P < .001) or ratio of allantoin/uric acid (P < .001) on infarct growth rate in women, but not in men.
“This exploratory reanalysis of the URICO-ICTUS trial highlighted the clinical value of the administration of [uric acid] in women with acute ischemic stroke who received thrombolysis within 4.5 hours of clinical onset,” the researchers wrote. “Given the major practical implications that could be derived in the field of acute ischemic stroke, larger confirmatory studies will be urgently required to confirm these encouraging results.” – by Jennifer Byrne
Disclosure: The researchers report no relevant financial disclosures.