Background Xanthine oxidase is involved in the production of uric acid and the generation of superoxide anion. We evaluated the long-term effect of febuxostat, a non-purine selective xanthine oxidase inhibitor,… Click to show full abstract
Background Xanthine oxidase is involved in the production of uric acid and the generation of superoxide anion. We evaluated the long-term effect of febuxostat, a non-purine selective xanthine oxidase inhibitor, on endothelial function in patients with asymptomatic hyperuricemia. Methods In the PRIZE study, patients with hyperuricemia were randomly assigned to either add-on febuxostat treatment (febuxostat group) or non-pharmacologic hyperuricemia treatment (control group). Among the 514 participants, endothelial function was assessed in 41 patients in the febuxostat group and 38 patients in the control group by flow-mediated vasodilation (FMD) of the brachial artery at the beginning of the study and after 12 and/or 24 months of treatment (63 men; median age, 68.0 years). Results The least squares mean concentration of serum uric acid was significantly lower in the febuxostat group than in the control group at 6 months (mean between-group difference [febuxostat group - control group], −2.09 mg/dL [95% confidence interval (CI), −2.520 to −1.659]; P < 0.001), 12 months (mean between-group difference, −2.28 mg/dL [95% CI, −2.709 to −1.842]; P < 0.001), and 24 months (mean between-group difference, −2.61 mg/dL [95% CI, −3.059 to −2.169]; P < 0.001). No significant differences were found between groups in the least squares mean estimated percentage change in FMD at 12 months (mean between-group difference, −0.56% [95% CI, −1.670 to 0.548]; P = 0.319) and at 24 months (mean between-group difference, −0.60% [95% CI, −1.886 to 0.685]; P = 0.357). Conclusion Febuxostat treatment did not alter endothelial function assessed by FMD during a 2-year study period in patients with asymptomatic hyperuricemia.
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