Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial

作者：Atsushi Tanaka, Isao Taguchi, Hiroki Teragawa, Nobukazu Ishizaka, Yumiko Kanzaki, Hirofumi Tomiyama, Masataka Sata, Akira Sezai, Katsumi Eguchi, Toru Kato, Shigeru Toyoda, Ryoichi Ishibashi, Kazuomi Kario, Tomoko Ishizu, Shinichiro Ueda, Koji Maemura, Yukihito Higashi, Hirotsugu Yamada, Mitsuru Ohishi, Kotaro Yokote, Toyoaki Murohara, Jun‐ichi Oyama, Koichi Node, on behalf of the PRIZE study investigators · 发表于：PLoS Medicine · 年份：2020 · DOI：10.1371/journal.pmed.1003095 · 被引用次数：103 · 研究领域：Gout, Hyperuricemia, Uric Acid、Thyroid Disorders and Treatments、Sodium Intake and Health

BACKGROUND: An elevated level of serum uric acid (SUA) is associated with an increased risk of cardiovascular disease. Pharmacological intervention with urate-lowering agents, such as the conventional purine analogue xanthine oxidase (XO) inhibitor, allopurinol, has been used widely for a long period of time in clinical practice to reduce SUA levels. Febuxostat, a novel non-purine selective inhibitor of XO, has higher potency for inhibition of XO activity and greater urate-lowering efficacy than conventional allopurinol. However, clinical evidence regarding the effects of febuxostat on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia. METHODS AND FINDINGS: The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial undertaken at 48 sites throughout Japan between May 2014 and August 2018. Adults with both asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery (CCA) ≥1.1 mm at screening were allocated equally using a central web system to receive either dose-titrated febuxostat (10-60 mg daily) or as a control-arm, non-pharmacological lifestyle modification for hyperuricemia, such as a healthy diet and exercise therapy. Of the 514 enrolled participants, 31 were excluded from the analysis, with the remaining 483 people (mean age 69.1 years [standard deviation 1...