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SYSTEMATIC REVIEW article

Front. Cardiovasc. Med.

Sec. Cardiovascular Pharmacology and Drug Discovery

Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1541307

A Systematic Review and Network Meta-Analysis of Cardiovascular Safety of Benzbromarone compared to Febuxostat and Allopurinol in Patients with Gout

Provisionally accepted
Ting-Syuan LinTing-Syuan Lin1,2Yen-Liang LinYen-Liang Lin1,3Chiu-Hao HsuChiu-Hao Hsu1,4Song-Chou HsiehSong-Chou Hsieh5Wen-Yi ShauWen-Yi Shau1Wei-Shiung YangWei-Shiung Yang1,6Chi-Ling ChenChi-Ling Chen1,7*
  • 1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  • 2Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Bei-Hu branch, Taipei, Taiwan
  • 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Hsinchu County, Taiwan
  • 4Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Hsinchu County, Taiwan
  • 5Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 6Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 7Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

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Background: Gout is caused by hyperuricemia and is associated with cardiovascular diseases. Treatment for hyperuricemia primarily involves urate-lowering medications. Some trials showed higher cardiovascular mortality rates with febuxostat compared to allopurinol in gout patients. However, data on the cardiovascular safety of benzbromarone compared to allopurinol is limited, and there is no data comparing benzbromarone to febuxostat. This study aims to assess the cardiovascular safety of benzbromarone, febuxostat, and allopurinol in gout patients.Methods: A comprehensive search was conducted across PubMed and EMBASE from their inception to August 2024. Inclusion criteria were randomized controlled trials (RCTs) and cohort studies including adult patients with the diagnosis of gout, with urate-lowering medications. The outcome was the incidence of major adverse cardiovascular events. This systematic review and network meta-analysis were recorded in INPLASY with the ID INPLASY202460049.Results: A total of 176 studies were identified through the database search. There were 119 articles identified in EMBASE and 57 articles identified in PubMed. Following screening and review, 17 qualified studies (5 RCTs) were included in the network meta-analysis. The relative cardiovascular event risk (risk ratio, RR) for benzbromarone compared to febuxostat is 0.82 (95% CI 0.61-1.09), and for benzbromarone compared to allopurinol, the RR is 0.87 (95% CI 0.75-1.01). The RR for febuxostat compared to allopurinol is 1.08 (95% CI 0.97-1.20).Our network meta-analysis suggests a subtle trend indicating a lower risk of cardiovascular events for benzbromarone compared to both febuxostat and allopurinol in gout patients, although not statistically significant.

Keywords: Febuxostat, Allopurinol, Benzbromarone, cardiovascular, Gout

Received: 07 Mar 2025; Accepted: 27 Jun 2025.

Copyright: © 2025 Lin, Lin, Hsu, Hsieh, Shau, Yang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chi-Ling Chen, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 10617, Taiwan

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material