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

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.

Conclusions: Among hyperuricemic patients, febuxostat was associated with favorable cardiovascular and cerebrovascular outcomes as compared with allopurinol.

Keywords: Antagonists and inhibitors; Cardiovascular system; Long-term effects; National health insurance; Xanthine oxidase.