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

Article English OPEN
Muir, S.W. ; Harrow, C. ; Dawson, J. ; Lees, K.R. ; Weir, C.J. ; Sattar, N. ; Walters, M.R. (2008)

<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>\ud \ud <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>\ud \ud <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>\ud \ud <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>
  • References (21)
    21 references, page 1 of 3

    1. Dawson J, Walters MR. Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol. 2006;62:633- 644.

    2. Weir CJ, Muir SW, Walters MR, Lees KR. Serum urate as an independent predictor of poor outcome and vascular events after acute stroke. Stroke. 2003;34:1951-1957.

    3. Cherubini A, Polidori MC, Bregnocchi M, Pezzuto S, Cecchetti R, Ingegni T, di Iorio A, Senin U, Mecocci P. Antioxidant profile and early outcome in stroke patients. Stroke. 2003;31:2295-2300.

    4. Chamorro A, Obach V, Cervera A, Revilla M, Deulofeu R, Aponte JH. Prognostic significance of uric acid serum concentration in patients with acute ischemic stroke. Stroke. 2002;33:1048 -1052.

    5. Høiggen A, Alderman M, Kjeldsen SE, Julius S, Devereux RB, De Faire U, Fyhrquist F, Ibsen H, Kristianson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H, Chen C, Dahlo¨ f B; LIFE Study Group. The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int. 2004;65: 1041-1049.

    6. Berry C, Hamilton CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJV, Dominiczak AF. Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation. 2000;106:221-226.

    7. Dawson J, Quinn TQ, Walters MR. Xanthine oxidase inhibition-a new paradigm in management of cardiovascular risk. Curr Med Chem. 2007; 14:1879 -1886.

    8. Okamoto H, Mizuno K, Hori T. Monocytes-derived multinucleated giant cells and sarcoidosis. J Dermatol Sci. 2003;31:119 -128.

    9. Amaro S, Soy D, Obach V, Cervera A, Planas AM, Chamorro A. A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke. 2007;38:2173.

    10. George J, Carr E, Davies J, Belch JJF, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114:2508 -2516.

  • Metrics
    No metrics available
Share - Bookmark