The influence of febuxostat on coronary artery endothelial dysfunction in patients with coronary artery disease: A phase 4 randomized, placebo-controlled, double-blind, crossover trial.

ABSTRACT

BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.