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(Stroke. 2008;39:3303.)
© 2008 American Heart Association, Inc.

Original Contributions

Allopurinol Use Yields Potentially Beneficial Effects on Inflammatory Indices in Those With Recent Ischemic Stroke

A Randomized, Double-Blind, Placebo-Controlled Trial

Scott W. Muir, MRCP; Craig Harrow, MRCP; Jesse Dawson, MRCP; Kennedy R. Lees, MD, FRCP; Christopher J. Weir, PhD; Naveed Sattar, PhD, FRCP Matthew R. Walters, MD, FRCP

From the Acute Stroke Unit, Division of Cardiovascular and Medical Sciences (S.W.M., C.H., J.D., K.R.L., M.R.W.), the Robertson Centre for Biostatistics (C.J.W.), and the BHF Glasgow Cardiovascular Research Centre (N.S.), University of Glasgow, Glasgow, UK.

Correspondence to Jesse Dawson, MRCP, Acute Stroke Unit, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, G11 6NT UK. E-mail j.dawson{at}clinmed.gla.ac.uk

Background and Purpose— Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke.

Methods— We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks’ treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke.

Results— We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test).

Conclusion— Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.

Key Words: stroke management • uric acid • xanthine oxidase