Optimal uric acid levels by febuxostat treatment and cerebral, cardiorenovascular risks: post hoc analysis of a randomized controlled trial

被引：11

作者：

Kojima, Sunao ^{[1
]}

Uchiyama, Kazuaki ^{[2
]}

Yokota, Naoto ^{[3
]}

Tokutake, Eiichi ^{[4
]}

Wakasa, Yutaka ^{[5
]}

Hiramitsu, Shinya ^{[6
]}

Waki, Masako ^{[7
]}

Jinnouchi, Hideaki ^{[8
]}

Kakuda, Hirokazu ^{[9
]}

Hayashi, Takahiro ^{[10
]}

Kawai, Naoki ^{[11
]}

Sugawara, Masahiro ^{[12
]}

Mori, Hisao ^{[13
]}

Tsujita, Kenichi ^{[14
]}

Matsui, Kunihiko ^{[15
]}

Hisatome, Ichiro ^{[16
]}

Ohya, Yusuke ^{[17
]}

Kimura, Kazuo ^{[18
]}

Saito, Yoshihiko ^{[19
]}

Ogawa, Hisao ^{[20
]}

机构：

[1] Sakurajyuji Yatsushiro Rehabil Hosp, Dept Internal Med, 2-4-33 Honmachi, Yatsushiro 8660861, Japan

[2] Uchiyama Clin, Yoshikawa Ku, Joetsu, Japan

[3] Yokota Naika, Hanagashima Cho, Miyazaki, Japan

[4] Tokutake Iin, Kawaguchi, Saitama, Japan

[5] Wakasa Med Clin, Kanazawa, Ishikawa, Japan

[6] Hiramitsu Heart Clin, Nagoya, Aichi, Japan

[7] Shizuoka City Shizuoka Hosp, Shizuoka, Japan

[8] Jinnouchi Hosp Diabet Care Ctr, Kumamoto, Japan

[9] Kakuda Iin, Kaho Ku, Takamatsu, Kagawa, Japan

[10] Hayashi Med Clin, Sakai, Osaka, Japan

[11] Kawai Naika Clin, Gifu, Japan

[12] Sugawara Clin, Nerima Ku, Kyoto, Japan

[13] Fuji Hlth Promot Ctr, Fuji, Shizuoka, Japan

[14] Kumamoto Univ, Dept Cardiovasc Med, Kumamoto, Japan

[15] Kumamoto Univ Hosp, Dept Family Community & Gen Med, Kumamoto, Japan

[16] Tottori Univ, Inst Regenerat Med & Biofunct, Grad Sch Med Sci, Yonago, Tottori, Japan

[17] Univ Ryukyus, Dept Cardiovasc Med Nephrol & Neurol, Sch Med, Nishihara, Okinawa, Japan

[18] Yokohama City Univ, Div Cardiol, Med Ctr, Yokohama, Kanagawa, Japan

[19] Nara Med Univ, Dept Cardiovasc Med, Kashihara, Nara, Japan

[20] Kumamoto Univ, Kumamoto, Japan

来源：

RHEUMATOLOGY | 2022年 / 61卷 / 06期

关键词：

febuxostat; hyperuricaemia; hypouricaemia; kidney; serum uric acid; FREED; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; AMERICAN-COLLEGE; ALL-CAUSE; HYPERTENSION; MANAGEMENT; HYPERURICEMIA; GUIDELINE; MORTALITY;

D O I：

10.1093/rheumatology/keab739

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives. Hyperuricaemia is recognized as an independent risk marker for cardiovascular and renal diseases. However, uric acid is a powerful free-radical scavenger, and the optimal level of serum uric acid (SUA) determining outcomes is unknown. This study explored whether interventional treatments for excessive SUA reduction were harmful and what constituted the optimal lowering of SUA levels for the prevention of events in patients with asymptomatic hyperuricaemia. Methods. This was a post hoc analysis of a randomized trial (Febuxostat for Cerebral and Candiorenovascular Events PrEvEntion StuDy [FREED]) in which 1070 older patients with asymptomatic hyperuricaemia were enrolled and allocated to febuxostat (n = 537) or non-febuxostat treatment group (n = 533). We assessed the relationship between the endpoint (withdrawal or study completion) SUA levels and clinical outcomes. Primary endpoint was defined as a composite of all-cause mortality, cerebral and cardiorenovascular events. Results. In the febuxostat group, patients achieving SUA levels <= 4 mg/di (hazard ratio: 2.01 [95% CI: 1.05, 3.87]), >4 to <= 5 mg/di (2.12 [1.07, 4.20], >6 to <= 7 mg/di (2.42 [1.05, 5.60]), and >7 mg/di (4.73 [2.13, 10.5]) had significantly higher risks for a primary composite event than those achieving SUA levels >5 to <= 6 mg/dl (P = 0.003 [log-rank test]). This J-shaped relationship applied to patients with renal impairment (P = 0.007 [Gray's test]) and was not significant in the non-febuxostat treatment group (P = 0.212 [log-rank test]). Conclusion. Optimal SUA level by febuxostat treatment is 5-6 mg/dl for reducing all-cause mortality, cerebral, cardiovascular and renal events. Excessive SUA reduction may be harmful in older hyperuricaemic populations.

引用

页码：2346 / 2359

页数：14