Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial

Muir, S.W., Harrow, C., Dawson, J. , Lees, K.R., Weir, C.J., Sattar, N. and Walters, M.R. (2008) Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial. Stroke, 39(12), pp. 3303-3307. (doi:10.1161/STROKEAHA.108.519793)

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Publisher's URL: http://dx.doi.org/10.1161/STROKEAHA.108.519793

Abstract

<p><b>Background and Purpose</b>: 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.</p> <p><b>Methods</b>: 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.</p> <p><b>Results</b>: 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).</p> <p><b>Conclusion</b>: 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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lees, Professor Kennedy and Dawson, Professor Jesse and Sattar, Professor Naveed and Muir, Dr Scott and Walters, Professor Matthew
Authors: Muir, S.W., Harrow, C., Dawson, J., Lees, K.R., Weir, C.J., Sattar, N., and Walters, M.R.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Stroke
Publisher:American Heart Association
ISSN:0039-2499
ISSN (Online):1524-4628
Published Online:09 October 2008
Copyright Holders:Copyright © 2008 American Heart Association
First Published:First published in Stroke 39(12):3303-3307
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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