The effect of allopurinol on the cerebral vasculature of patients with subcortical stroke; a randomized trial
Article first published online: 21 JUL 2009
© 2009 The Authors. Journal compilation © 2009 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 68, Issue 5, pages 662–668, November 2009
How to Cite
Dawson, J., Quinn, T. J., Harrow, C., Lees, K. R. and Walters, M. R. (2009), The effect of allopurinol on the cerebral vasculature of patients with subcortical stroke; a randomized trial. British Journal of Clinical Pharmacology, 68: 662–668. doi: 10.1111/j.1365-2125.2009.03497.x
- Issue published online: 6 NOV 2009
- Article first published online: 21 JUL 2009
- Received 10 April 2009Accepted6 July 2009
- uric acid;
- xanthine oxidase
WHAT IS ALREADY KNOWN ABOUT THE SUBJECT
• The therapeutic potential of xanthine oxidase inhibition with allopurinol in vascular disease is increasingly apparent.
• Allopurinol has been shown to improve measures of peripheral vascular function in those with and at risk of cardiac disease and stroke.
• It has also been shown to improve cerebrovascular function in those with diabetes, but no study has assessed its effect on cerebrovascular function in those with previous stroke.
WHAT THIS PAPER ADDS
• This study did not confirm a beneficial effect of allopurinol on cerebrovascular reactivity.
• This raises the possibility that previous encouraging findings will not therefore translate into important clinical benefits.
• Results of this and other trials suggest allopurinol may be most effective in those with increased serum uric acid levels, but cast doubt over whether previous positive effects will be sustained over a prolonged period.
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.
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.
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.
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.