Effects of allopurinol on endothelial dysfunction: a meta-analysis.

Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation.
Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ(2) statistic (with substantial heterogeneity defined as values >50%).
The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ(2) = 319.1, I(2) = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ(2) = 9.0, I(2) = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation.
We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.
AuthorsMehmet Kanbay, Dimitrie Siriopol, Ionut Nistor, Omer C Elcioglu, Ozge Telci, Mumtaz Takir, Richard J Johnson, Adrian Covic
JournalAmerican journal of nephrology (Am J Nephrol) Vol. 39 Issue 4 Pg. 348-56 ( 2014) ISSN: 1421-9670 [Electronic] Switzerland
PMID24751886 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
Chemical References
  • Gout Suppressants
  • Allopurinol
  • Allopurinol (pharmacology, therapeutic use)
  • Cardiovascular Diseases (prevention & control)
  • Endothelium, Vascular (drug effects)
  • Gout Suppressants (pharmacology, therapeutic use)
  • Humans
  • Hyperuricemia (drug therapy)
  • Vasodilation (drug effects)

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