Abstract
Rationale & ObjectiveAllopurinol and febuxostat, which are xanthine oxidoreductase inhibitors, have been widely used as uric acid-lowering medications. However, evidence regarding their cardiovascular effects in hemodialysis is insufficient. This study compared the effects of allopurinol and febuxostat on mortality and cardiovascular outcomes in patients receiving hemodialysis. Study DesignRetrospective observational cohort study. Setting & ParticipantsData of 6,791 patients who had no history of topiroxostat usage and underwent maintenance hemodialysis between March 2016 and March 2019 at Yokohama Daiichi Hospital, Zenjinkai, and its affiliated dialysis clinics in Japan’s Kanagawa and Tokyo metropolitan areas were collected. ExposureAllopurinol, febuxostat, and non-treatment. OutcomesAll-cause mortality, cardiovascular disease (CVD) events, heart failure (HF), acute myocardial infarction (AMI), and stroke. Analytical ApproachFor the main analyses, marginal structural Cox proportional hazards models were used to estimate hazard ratios (HRs) adjusted for time-varying confounding and selection bias due to censoring. ResultsAllopurinol and febuxostat showed significantly better survival than non-treatment for all-cause mortality (HR: 0.40, 95% confidence interval [CI]: 0.30–0.54; HR: 0.49, 95% CI: 0.38–0.63, respectively), without significant difference between allopurinol and febuxostat. Allopurinol showed significantly better survival than non-treatment, whereas febuxostat did not for CVD events (HR: 0.89, 95% CI: 0.84–0.95; HR: 1.01, 95% CI: 0.96–1.07, respectively), HF (HR: 0.71, 95% CI: 0.56–0.90; HR: 1.03, 95% CI: 0.87–1.21, respectively), and AMI (HR: 0.48, 95% CI: 0.25–0.91; HR: 0.76, 95% CI: 0.49–1.19, respectively). No comparisons showed significant results for stroke. LimitationsThe ratio of renal or intestinal excretion of uric acid and uremic toxins could not be elucidated, and we could not investigate gene polymorphism because of the large number of cases. ConclusionsAllopurinol and febuxostat improved survival for all-cause mortality. Allopurinol, and not febuxostat, reduced the risk of CVD events, HF, and AMI.
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