Cardiovascular outcomes of febuxostat and allopurinol: A long-term Taiwanese nationwide cohort study

Tsung‐Lin Yang; Hsin‐Bang Leu; Shing-Jong Lin; Jiun‐Lin Horng; Chun-Ming Shih

doi:10.1016/j.jfma.2025.05.040

June 2, 2025Journal of the Formosan Medical AssociationOpen Access

Cardiovascular outcomes of febuxostat and allopurinol: A long-term Taiwanese nationwide cohort study

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Why the study?

Studies with larger cohorts and longer follow-up periods are required to evaluate the cardiovascular safety of febuxostat and allopurinol.

Does febuxostat reduce the composite of nonfatal MI, nonfatal ischemic stroke, and cardiovascular death compared to allopurinol in hyperuricemic patients?

Structured PICO

Does febuxostat reduce the composite of nonfatal MI, nonfatal ischemic stroke, and cardiovascular death compared to allopurinol in hyperuricemic patients?

P

Population

130,092 hyperuricemic patients (65,046 per group) from the Taiwan National Health Insurance Research Database

I

Intervention

Febuxostat

C

Comparator

Allopurinol

O

Outcome

Composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular deathcomposite

In a large Taiwanese cohort, febuxostat was associated with a significantly lower risk of major cardiovascular events compared to allopurinol, primarily driven by a reduction in ischemic stroke.

Implication

May support febuxostat preference in hyperuricemia; leaves open need for prospective RCTs before practice change.

Abstract

INTRODUCTION: Studies with larger cohorts and longer follow-up periods are required for cardiovascular safety of febuxostat and allopurinol. MATERIAL AND METHODS: This population-based, retrospective study was conducted with the Taiwan National Health Insurance Research Database. The primary outcome was a composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. The secondary outcomes were subsequent atrial fibrillation or heart failure hospitalization, all-cause mortality, and a composite of major cardiovascular and cerebrovascular events. RESULTS: A total of 65,046 patients were included in each group, and baseline characteristics were well matched. After a maximum follow-up of 6.7 years (mean: 2.4 and 4.1 years in the febuxostat and allopurinol groups), the incidence of the primary outcome was significantly lower in the febuxostat users than in the allopurinol users (1000 person-year incidence rate: 16.09 versus 16.32, hazard ratio [HR] 0.93, 95 % confidence interval [CI], 0.87-0.99; p = 0.028), with the difference mainly driven by lower ischemic stroke risk in febuxostat users. Febuxostat had lower risks of events among the elderly, female gender and those with diabetes or chronic kidney disease in subgroup analysis. After multivariate adjustment, febuxostat was associated with significantly lower risks of ischemic stroke, major adverse cardiovascular events, and major adverse cardiovascular and cerebrovascular events. Both allopurinol and febuxostat did not show a dose-dependent response. CONCLUSION: Among hyperuricemic patients, febuxostat was associated with favorable cardiovascular and cerebrovascular outcomes as compared with allopurinol.