Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study

Kenya Kusunose,Daigaku Uchida,Yoshisato Shibata,Mami Enomoto,Shuichi Fujita,Ai Tamura,Toyoaki Murohara,Tomomi Matsuura,Mieko Fukui,Yuichi Fujii,Kotaro Yokote,Takashi Ishimatsu,Wataru Shimizu,Jiko Yamada,Akihito Tanaka,Sadako Takahashi,Yusuke Ohya,Satoshi Kodera,Kazutaka Aonuma,Shio Oguchi,Kuniya Asai,Shinichi Niwano,Hiroko Ishigami,Arihide Okahara,Hidemitsu Nakagawa,Takahide Ito,Shingo Kono,Masatoshi Miyamura,Akifumi Kushiyama,Hiroaki Sano,Mitsuru Ohishi,Munehide Matsuhisa,Toshiaki Ban,Daiju Fukuda,Masaaki Okutsu,Seiji Koga,Kaoru Takegami,Daigo Mine,Kazushi Sakane,Soichiro Kashihara,Yoshiaki Kubota,Eri Komai,Teruo Inoue,Takanori Kuroyanagi,Masahisa Shimpo,Hidekazu Nagano,Hirohisa Amano,Bonpei Takase,Tomohiro Fujisaka,Satoshi Hoshide,Tomoya Hara,Hisakuni Sekino,Michio Shimabukuro,Nozomu Oda,Yutaka Aoyama,Isao Yaguchi,Takeshi Soeki,Mitsutoshi Oguri,Ayumi Ito,Tazu Tahara,Hirotaka Watada,Kyohei Yamamoto,Masato Watarai,Hiroyuki Daida,Akio Kuroda,Tomoaki Tanaka,Akihiro Honda,Yusuke Ishiyama,Yoshihiko Sakai,Kazuki Shiina,Toshiaki Kadokami,Fumitake Ozaki,Tomohiro Ueda,Hisashi Koide,Junko Hotchi,Chikara Ueyama,Daisuke Tanimura,Hirofumi Arai,Makoto Suzuki,Ryo Nakamura,Tomoyuki Tobushi,Mitsumasa Hata,Shuichi Hamasaki,Kazuo Kitagawa,Akina Shiga,Yuichi Saito,Masaharu Ishihara,Akinori Fujikake,Youhei Inoue,Shinichiro Ueda,Iichiro Shimomura,Kazuo Matsunaga,Koji Maemura,Yuka Senoo,Hideaki Morita,Takahisa Shibata,Masanori Fujimoto,Isao Nishi,Kensaku Shibata,Yumi Ikehara,Naoto Yokota,Katsunori Nakamura,Shunsuke Eguchi,Yosuke Tatami,Yuhei Goriki,Sachiko Yamauchi,Yoshifumi Awaji,Ryo Hayashida,Goro Yoshioka,Tetsuzo Wakatsuki,Takashi Terano,Junya Ako,Yusaku Shimbo,Yuji Koide,Shiro Hata,Nobuhiro Tahara,Michishige Ozeki,Makoto Saitoh,Satoki Fukae,Jun Tanigawa,Hiroyuki Suzuki,Yoshio Kobayashi,Machiko Asaka,Takafumi Mayama,Hiroshi Koiwaya,Mikiko Kagiyama,Sachiyo Igata,Tomoko Ishizu,Tomoko Saisu,Hiroki Kojima,Tatsuya Maruhashi,Masaaki Hoshiga,Fumio Terasaki,Rie Ueno,Yohei Yamauchi,Koichi Sohmiya,Seiko Tokoi,Hiroyuki Tanaka,Yosuke Saka,Hitoshi Nakashima,Ikuko Nakamura,Shakya Sandeep,Tetsuya Ishikawa,Hideki Ishii,Mamoru Nanasato,Hiroshi Hasegawa,Hiromi Ueno,Tomonobu Takikawa,Tomohikov Yoshida,Ayumu Yajima,Tetsuya Watanabe ,Katsumi Eguchi ,Kazuomi Kario,Ichiro Sakuma ,Masataka Sata,Ryo Morimoto ,Jun‐Ichi Oyama ,Nenad Ban ,Yasuko K Bando ,Hirotsugu Yamada,Hiroki Teragawa,Kazuhito Hashimoto ,Haruhiko Yoshida ,Sadahiro Nomura ,Toshimitsu Komatsu ,Takashi Kobayashi ,Tetsuya Takiguchi ,Atsushi Tanaka,Shigekazu Higuchi ,Yuichi Akasaki,Hajime Kamiya ,Koichi Node,Shinya Suzuki ,Yoshihiro Fukumoto,Y Kawamura ,Akira Higashi ,Takashi Tsubouchi

doi:10.1038/s41440-021-00752-9

Abstract

Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e′ between the two groups from baseline to 24 months. Interestingly, e′ was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e′ (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

Highlights

A list of authors and their affiliations appears below the Acknowledgement Section.Hyperuricemia can be associated with cardiometabolic abnormalities and the association leads to the development of atherosclerosis and resultant cardiovascular disease10 Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan [1,2,3]
5 Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Hyperuricemia can be associated with cardiometabolic abnormalities and the association leads to the development of atherosclerosis and resultant cardiovascular disease
To elucidate the effect of febuxostat on echocardiographic parameters, we investigated the effect of the febuxostat on 2-dimensional and Doppler echocardiographic parameters and biomarkers from baseline to 24 months as a prespecified endpoint in the subanalysis of the PRIZE study (University Hospital Medical Information Network Clinical Trial Registry UMIN000041322)

Summary

Introduction

A list of authors and their affiliations appears below the Acknowledgement Section. Hyperuricemia can be associated with cardiometabolic abnormalities and the association leads to the development of atherosclerosis and resultant cardiovascular disease. Several studies investigated the association between hyperuricemia and echocardiographic variables [4,5,6,7]. Krishnan et al showed the correlation between the left ventricular (LV) mass index and serum uric acid (SUA) level [8]. Lin et al showed the LV diastolic functional parameters were associated with gout [9]. The association between hyperuricemia and cardiac function is a key mechanism of hyperuricemia on cardiovascular diseases. It is clinically required to evaluate the impact of antihyperuricemia agents on cardiac function from the randomized cohort study

Methods

Results

Conclusion