The effect of allopurinol on the cerebral vasculature of patients with subcortical stroke; a randomized trial.
OBJECTIVE
New preventative strategies for stroke are required. One promising strategy is uric acid reduction and xanthine oxidase inhibition with allopurinol. We sought to investigate whether allopurinol improves cerebrovascular reactivity (CVR) following subcortical stroke.


METHODS
We performed a randomized, double-blind, controlled study to investigate the effect of a 3-month course of 300 mg allopurinol once daily vs. placebo on CVR in individuals with recent (within 6 months) subcortical stroke. Participants were randomized on a 1:1 basis. CVR was defined as the percentage change in middle cerebral artery flow velocity following an intravenous injection of 15 mg kg(-1) of acetazolamide. Our primary end-point was the CVR difference between baseline and 3 months. Secondary end-points included measures of peripheral vascular reactivity and blood markers of inflammation and endothelial activation.


RESULTS
We enrolled 50 participants; 45 completed the protocol. Baseline serum urate was 0.35 mmol l(-1) (SD 0.1) and 0.34 mmol l(-1) (SD 0.1) in the allopurinol and placebo groups, respectively. There were no serious adverse events related to treatment. CVR did not change following treatment with allopurinol [median CVR change 0.89% after allopurinol (n = 20) and -0.68% after placebo (n = 25); 95% confidence interval for estimated difference in medians -13.4, 25.5, P = 0.64]. Urate was significantly lowered by allopurinol but no change in other secondary end-points was seen.


CONCLUSIONS
Xanthine oxidase inhibition with allopurinol has previously been shown to improve cerebrovascular function, but no benefit was seen in this study. It may therefore be that previous encouraging findings will not translate into important clinical benefits.
Dawson
Jesse
J
Acute Stroke Unit, Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Western Infirmary, Glasgow, UK. j.dawson@clinmed.gla.ac.uk
Quinn
Terrence J
TJ
Harrow
Craig
C
Lees
Kennedy R
KR
Walters
Matthew R
MR
D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D013223:Statistics as Topic; D020521:Stroke / Q000188:drug therapy*; D014527:Uric Acid / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase