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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 5/2023

01-06-2022 | Xanthine Oxidase Inhibitors | Original Article

C-reactive Protein Levels and Cardiovascular Outcomes After Febuxostat Treatment in Patients with Asymptomatic Hyperuricemia: Post-hoc Analysis of a Randomized Controlled Study

Authors: 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, on behalf of the Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) investigators

Published in: Cardiovascular Drugs and Therapy | Issue 5/2023

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Abstract

Purpose

Inflammation plays an important role in the initiation and progression of atherosclerosis, leading to poor clinical outcomes. Hyperuricemia is associated with the activation of the Nod-like receptor protein 3 inflammasome. Here, we investigated whether inhibition of inflammation using febuxostat lowered the risk of cardiovascular events.

Methods

This is a post-hoc analysis of the randomized trial, Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED). In total, 1067 patients (736 men and 331 women) were included in the analysis. We compared the serial changes in high-sensitivity C-reactive protein (hs-CRP) levels between febuxostat and non-febuxostat groups and assessed the correlation between the changes in uric acid (UA) and hs-CRP levels after febuxostat treatment. We also determined whether febuxostat could reduce a hard endpoint, defined as a composite of cardiovascular events and all-cause mortality.

Results

Serum UA levels in the febuxostat group were significantly lower than those in the non-febuxostat group after randomization (p < 0.05). However, hs-CRP levels were comparable between the two groups during the study. No significant correlation was observed between the changes in UA and hs-CRP levels after febuxostat treatment. The hard endpoints did not differ significantly between the two groups. In patients with baseline hs-CRP levels > 0.2 mg/dL or those administered 40 mg of febuxostat, the drug did not reduce hs-CRP levels or decrease the hard endpoint.

Conclusion

Febuxostat reduced the UA levels but did not affect the CRP levels, and therefore may fail to improve cardiovascular outcomes after treatment.

Trial Registration

ClinicalTrial.gov (NCT01984749). https://clinicaltrials.gov/ct2/show/NCT01984749
Appendix
Available only for authorised users
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Metadata
Title
C-reactive Protein Levels and Cardiovascular Outcomes After Febuxostat Treatment in Patients with Asymptomatic Hyperuricemia: Post-hoc Analysis of a Randomized Controlled Study
Authors
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
on behalf of the Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) investigators
Publication date
01-06-2022
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 5/2023
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-022-07347-7

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