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


CONCLUSIONS
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.
Muir
Scott W
SW
Division of Cardiovascular and Medical Sciences, Acute Stroke Unit, University of Glasgow, Western Infirmary, Glasgow, UK.
Harrow
Craig
C
Dawson
Jesse
J
Lees
Kennedy R
KR
Weir
Christopher J
CJ
Sattar
Naveed
N
Walters
Matthew R
MR
D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D014527:Uric Acid / Q000097:blood*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D014527:Uric Acid; D000493:Allopurinol; D002097:C-Reactive Protein; D014969:Xanthine Oxidase