Xanthine oxidase inhibition for the treatment of cardiovascular disease: a systematic review and meta-analysis

Abstract

Background: Xanthine oxidase inhibition (XOI) reduces oxidative stress in the vasculature. Moreover it reduces uric acid levels, a risk factor for the development of cardiovascular disease. As such, XOI holds a potentially dual mechanism for the treatment of cardiovascular disease.

Aims: Through systematic review, we sought to clarify the extent of available evidence that has evaluated the effect of XOI upon clinical or surrogate markers of cardiovascular disease and function in humans.

Methods: A systematic search strategy was used to interrogate the Ovid Medline (1950-June Week 4 2010) and Embase (1980-2010 Week 25) databases, to identify relevant studies. Meta-analysis was planned for frequently studied endpoints.

Results: Thirty-eight publications (reporting 40 studies) were identified. There was heterogeneity between studies in all aspects of study design, including the outcome measures of interest. Prospective assessment of surrogate markers predominated. Combined meta-analysis was feasible for three outcome parameters, with favorable modifications in each following xanthine oxidase inhibition: brachial artery flow mediated dilatation (five studies: XOI n = 75, control n = 69) increased by 2.50% (95% CI, 0.15-4.84); forearm blood flow responses to acetylcholine infusion (five studies: XOI n = 74, control n = 74) increased by 68.80 (95% CI, 18.70-118.90; percent change relative to noninfused control arm); circulating markers of oxidative stress (malondialdehyde, six studies: XOI n = 78, control n = 68) reduced by 0.56 nmol/mL (95% CI, 0.26-0.87).

Conclusions: XOI improves endothelial function and circulating markers of oxidative stress in patients with, or at risk of, cardiovascular disease. Large prospective studies examining definitive end points are lacking but now appear indicated.