1. While there was no placebo control group, treatment with febuxostat for 24 months did not slow carotid atherosclerosis progression in Japanese individuals with asymptomatic hyperuricemia.
Evidence Rating Level: 2 (Good)
Allopurinol, a purine analogue xanthine oxidase (XO) inhibitor, is a conventional pharmacological intervention for reducing serum uric acid (SUA) levels, which increases risk of cardiovascular disease. Febuxostat, a novel non-purine selective inhibitor of XO, has been found to have greater efficacy in lowering urate and a higher potency for XO inhibition. However, little is known regarding febuxostat and its role in atherosclerosis. This prospective, randomized, open-label, blinded-endpoint clinical trial occurring at 48 sites in Japan between May 2014 and August 2018 sought to examine the relationship between febuxostat and atherosclerosis through measuring carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia. A total of 483 adult participants (mean [SD] age = 69.1 [10.4] years, 19.7% female) with both maximum IMT of common carotid artery (CCA; ≥ 1.1 mm) and asymptomatic hyperuricemia (SUA ≥ 7.0 mg/dL) were allocated to either dose-titrated febuxostat (n = 239; 10 to 60 mg daily) or a non-pharmacological lifestyle modification for hyperuricemia (n = 244; e.g., diet, exercise changes) based on an intention-to-treat principle. Primary endpoint was change in mean IMT of the CCA from baseline to 24 months, with age, gender, history of type II diabetes, baseline SUA and IMT of the CCA as covariates. No significant differences between groups regarding CCA-IMT were found at baseline (p = 0.65). At 24 months, between group differences were not significant (mean difference -0.016 mm, 95% CI -0.051 to 0.019 mm, p = 0.37). Febuxostat did not demonstrate significant effects on the primary endpoint compared to the control group, nor did it have effects on other carotid ultrasonographic parameters. Regarding mean SUA values at 24 months, the febuxostat group was significantly lower than the control group (mean difference -2.62, 95% CI -2.86 to -2.38, p<0.001). While this study did not include a placebo control group, findings still suggest that 24 months of febuxostat treatment does not slow carotid atherosclerosis progression in Japanese individuals with asymptomatic hyperuricemia.
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