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

2021; Oxford University Press; Volume: 61; Issue: 6 Linguagem: Inglês

10.1093/rheumatology/keab739

1462-0332

Sunao Kojima, Kazuaki Uchiyama, Naoto Yokota, Eiichi Tokutake, Yutaka Wakasa, Shinya Hiramitsu, Masako Waki, Hideaki Jinnouchi, Hirokazu Kakuda, Takahiro Hayashi, Naoki Kawai, Masahiro Sugawara, Hisao Mori, Kenichi Tsujita, Kunihiko Matsui, Ichiro Hisatome, Yusuke Ohya, Kazuo Kimura, Yoshihiko Saito, Hisao Ogawa, Itaru Maeda, Hiroki Matsui, Toshiya Okamoto, Hideaki Omiya, Fumihiko Takeda, Hiroki Takeda, Yasushi Suzuki, T Shimasaki, Chikako Kaneko, M. Yamaki, Fumio Naganuma, Masayuki Nakano, Takeshi Maki, Nobuyuki Enomoto, Toshibumi Hogi, Kouichi Kanouzawa, Yasushi Okuaki, Tomoyuki Shibuya, Eiichi Tokutake, M Yanagisawa, Tetsuichi Asano, Masaki Akahata, Takao Baba, Yoshiaki Harada, Atsuhiro Ichihara, Yukinobu Kobayashi, Hitoshi Kurumatani, Masaki Miyahara, Shigeki Moritani, Kunihiko Ohno, Takeshi Okuda, Y Osamura, M Otaki, Masahiro Sugawara, Hideaki Sudo, Kazumi Taguchi, Shukuko Tominaga, Himasatotoshi Watanabe, Kirino Yuuya, Keiichi Chin, Hirokuni Etsuda, Nobuo Hatori, Kumio Iroden, Yoshitaka Kamegaya, Hideki Kikuchi, Kazuo Kimura, Hisao Mori, Takao Nagasu, Riichirou Nakayama, Masato Nishimura, Masahisa Ori, Kenji Tani, Hareaki Yamamoto, Jun Yamagami, Shohei Yuasa, Kazuaki Uchiyama, Kazuo Maeda, Hiroyuki Hayakawa, Hirokazu Kakuda, Shigeru Nakano, Toshiki Tatsumura, Yutaka Wakasa, Masayuki Yanagi, Masahiko Kuroda, Yasuhiko KAWADE, Naoki Kawai, Toshihide Kumazaki, Yoshiyuki Miwa, Yoshiki Noda, Masachika Sagoh, Minoru Sasaki, Kuniyuki Takai, Tomoo Takeda, Rieko Totani, Reiki Yoshida, Masaki Harada, Masako Waki, Riichiro Waki, Tomoharu Arakawa, Shinya Hiramitsu, Takuo Ogawa, Shinya Okamoto, Tsugio Isoda, Izuru Masuda, Ken Takenaka, Kaname Akioka, Takahiro Hayashi, Kazuo Ikeda, Hidetaka Kanazawa, Toru Kinugawa, Shoichi Kitano, Yoshiko Kubota, Yojiro KURIHARA, Miyuki Matsuo, Masayuki Matsushita, Hiroshi Nishimura, Toshihiko Seo, Masahiro Watanabe, Jun Arao, Tomohiro Katsuya, Naotaka Kusunose, Yuji Nakatani, Akira Nozaki, Nobushige Ote, Ken‐ichi Samejima, Kazuya Shigenobu, Hideo Ayame, Shoshi Matsuda, Takashi Fujimoto, Soichi Honda, Nobuaki Oka, Akira Ota, Osame Tanaka, Nobuo MATSUOKA, Kengo Matsumoto, Toshifumi Matsuno, Katsumi Yoshida, Hidetomo Maruyoshi, Seiichi Gotô, Youichi Hanaoka, Takatoshi Otonari, Koji Takaki, Masahiro Tohaya, Tetsuro Yoshida, K Honjo, Hideaki Jinnouchi, Hirofumi Kan, Shinobu Kojima, Akira Maki, Toshiro Matsunaga, Shuichi Matsuo, Hiroo Miyagi, Kunihiro Omori, Eiji Otsuka, Masamitsu Toihata, Kenichi Tsujita, Takuma Eto, Shuichi Kawano, Jyunichi Miyata, Naoto Yokota, Yusuke Oya, Sunao Kojima, Kazuaki Uchiyama, Naoto Yokota, Eiichi Tokutake, Yutaka Wakasa, Shinya Hiramitsu, Masako Waki, Hideaki Jinnouchi, Hirokazu Kakuda, Takahiro Hayashi, Naoki Kawai, Masahiro Sugawara, Hisao Mori, Ichiro Hisatome, Yusuke Ohya, Kazuo Kimura, Yoshihiko Saito, Hisao Ogawa, Yasuhiro Ogata, Satoru Yasuda, Toshiro Yonehara, Michihiro Yoshimura, Kunihiko Matsui, Yoichiro Hashimoto, Kazuteru Fujimoto, Tomohiro Sakamoto, Soichi Uekihara,

Alcohol Consumption and Health Effects

Abstract 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 CaRdiorenovascular 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/dl (hazard ratio: 2.01 [95% CI: 1.05, 3.87]), >4 to ≤5 mg/dl (2.12 [1.07, 4.20], >6 to ≤7 mg/dl (2.42 [1.05, 5.60]), and >7 mg/dl (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. Trial Registration ClinicalTrial.gov, https://clinicaltrials.gov, NCT01984749