SAN DIEGO—Administering uric acid along with t-PA to patients with stroke within 4.5 hours of symptom onset appears to be safe and effective at limiting disability, investigators reported at the 2014 International Stroke Conference.
In a study of 421 patients with acute stroke, approximately 40% of participants treated with uric acid and clot busters had a favorable outcome at 90 days, compared with 33% of patients treated with placebo. Favorable outcomes were defined as a modified Rankin scale (mRS) score of 0 to 1 or an mRS score of 2 in patients with a prior qualifying mRS score of 2. The difference between the two treatment arms was not statistically significant, however.
After treatment, the median mRS was 3 for controls and 2 for patients receiving uric acid. Uric acid produced the greatest benefits for women and patients with high blood sugar and moderate stroke. The drug was not associated with an increased risk of gout.
Patients Were Randomized to t-PA Plus Uric Acid or Placebo
“When used in stroke, uric acid is a firefighter, not an arsonist,” said Ángel Chamorro, MD, PhD, Director of the Comprehensive Stroke Center at Hospital Clinic in Barcelona. Extensive human and animal research found that a higher level of uric acid in patients with acute stroke was associated with better recovery, he added.
“Uric acid has a pretty bad reputation because it is associated with gout attacks, renal problems, and perhaps also with cardiovascular disease,” said Dr. Chamorro. “But what people do not know so well is that uric acid is an extremely potent antioxidant that prevents the formation of free radicals that can result when a brain artery is blocked.”
All patients received t-PA and were randomly assigned to receive uric acid or a placebo. Physicians assessed patients’ NIH Stroke Scale score at baseline, two hours, one day, two days, five days, and 90 days. Patients’ Barthel index and mRS scores were recorded at 90 days.
Half of patients in the study were women, and the average age of all patients was 76. Most participants had other medical conditions and were treated at 10 stroke centers in Spain. Approximately equal proportions of patients in both arms had high blood pressure, diabetes, and atrial fibrillation. Sixty patients died during the trial.
A Larger Trial Could Validate the Study’s Results
The study may explain why women have more disability after stroke than men. “We believe women are less equipped to combat oxidative stress as the result of their lower uric acid levels,” said Dr. Chamorro.
The study group was small, and the results will need validation in larger trials. The study’s strength, however, is that it involved elderly patients who had more serious strokes and other health problems, said Dr. Chamorro.
“We may need to acknowledge that there’s promise for uric acid in patients with acute stroke treated with a clot buster within 4.5 hours of symptom onset,” he observed. “The results of this trial are exciting and offer new hope in a field that was full of failures.”
—Erik Greb