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Febuxostat Leads to Better Cardiovascular Outcomes Compared to Allopurinol in Patients With Advanced Chronic Kidney Disease: A Population-Based Cohort Study - 10/02/25

Doi : 10.1016/j.amjmed.2024.09.018 
Ming-Hsien Tsai, MD, PhD a, b, Yun-Yi Chen, PhD c, d, Hung-Hsiang Liou, MD e, Jing-Tong Wang, AN a, Yu-Wei Fang, MD, PhD a, b,
a Division of Nephrology, Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan 
b Department of Medicine, Fu Jen Catholic University School of Medicine, New Taipei City, Taiwan 
c Department of Research, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan 
d Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan 
e Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan 

Requests for reprints should be addressed to: Yu-Wei Fang, MD, PhD, Division of Nephrology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.Division of NephrologyDepartment of Internal Medicine, Shin Kong Wu Ho-Su Memorial HospitalTaipeiTaiwan

Abstract

Objective

Hyperuricemia is a risk factor for cardiovascular disease complications in patients with chronic kidney disease. The impact of febuxostat on cardiovascular disease in advanced chronic kidney disease remains unclear. This study aimed to explore the cardiovascular benefits of xanthine oxidase inhibitors, particularly febuxostat and allopurinol, in patients with advanced chronic kidney disease.

Methods

A retrospective population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD) (2012–2020). The TriNetX dataset served as an external validation dataset. The study involved 13,187 patients with advanced chronic kidney disease treated with febuxostat or allopurinol. After propensity score matching, a balanced cohort of 976 patients (488 in each arm) was created. Hazard ratios (HRs) were calculated for all-cause mortality and hospitalizations, utilizing the competing risk regression model.

Results

Febuxostat was associated with lower all-cause mortality (HR, 0.79; 95% confidence interval [CI], 0.64-0.98) and fewer hospitalizations (HR, 0.53; 95% CI, 0.44-0.63) than allopurinol. After adjustments, febuxostat also reduced hospitalizations for heart failure (HR, 0.59; 95% CI, 0.43-0.80) and infection (HR, 0.65; 95% CI, 0.52-0.82). This cardiovascular benefit of febuxostat was consistently observed in the TriNetX dataset. Moreover, subgroup analysis revealed that febuxostat was better in reducing death and heart failure events than allopurinol across most of the subgroups.

Conclusions

Febuxostat may confer cardioprotective effects in patients with advanced chronic kidney disease compared with allopurinol, thereby making it potentially useful in reducing cardiovascular risks in this high-risk population.

El texto completo de este artículo está disponible en PDF.

Keywords : Advanced chronic kidney disease, Allopurinol, Cardiovascular diseases, Chronic kidney disease, Febuxostat, Hyperuricemia, Xanthine oxidase inhibitors


Esquema


 Funding: This study was supported by a grant under a cooperative project between Shin Kong Wu Ho-Su Memorial Hospital and National Yang Ming Chiao Tung University in Taiwan (109GB006-2) and Shin Kong Wu Ho-Su Memorial Hospital sponsored this study (2023SKHADR009). The funding source played no role in this study.
 Conflict of Interest: None.
 Authorship: M-HT: Writing—review and editing, Writing—original draft, Methodology, Funding acquisition, Conceptualization; Y-YC: Software, Investigation, Formal analysis; H-HL: Writing—review and editing, Methodology, Conceptualization; J-TW: Writing—review and editing, Project administration, Investigation; Y-WF: Writing—review and editing, Writing—original draft, Supervision, Methodology, Conceptualization.


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