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

Abstract

OBJECTIVE:

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.

METHODS:

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%).

RESULTS:

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.

CONCLUSIONS:

We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.

• Authors: Mehmet Kanbay, Dimitrie Siriopol, Ionut Nistor, Omer C Elcioglu, Ozge Telci, Mumtaz Takir, Richard J Johnson, Adrian Covic
• Journal: American journal of nephrology (Am J Nephrol) Vol. 39 Issue 4 Pg. 348-56 ( 2014) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 24751886 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Gout Suppressants
• Allopurinol

Topics

• Allopurinol (pharmacology, therapeutic use)
• Cardiovascular Diseases (prevention & control)
• Endothelium, Vascular (drug effects)
• Gout Suppressants (pharmacology, therapeutic use)
• Humans
• Hyperuricemia (drug therapy)
• Vasodilation (drug effects)