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

Allison Hays, Micaela Iantorno, Michael Schar, Shenghan Lai, Matthew Czarny, Elayne Breton, Robert N. Palmer, Andrew Whelton, Robert George Weiss, Gary Gerstenblith

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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 ± 0.8 mg/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.

Original languageEnglish (US)
Pages (from-to)85-93
Number of pages9
JournalAmerican Heart Journal
Volume197
DOIs
StatePublished - Mar 1 2018

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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