AJM online Clinical research study| Volume 128, ISSUE 6, P653.e7-653.e16, June 2015

Effects of Xanthine Oxidase Inhibitors on Cardiovascular Disease in Patients with Gout: A Cohort Study

Published:February 03, 2015DOI:



      Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.


      We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.


      There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.


      Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.


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      Linked Article

      • Effects of Xanthine Oxidase Inhibitors on Cardiovascular Disease in Patients with Gout: Ascertaining the Efficacy of Treatment Matters
        The American Journal of MedicineVol. 128Issue 9
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          We read with interest the article by Kim et al1 about the potential effect of xanthine oxidase inhibitors in reducing cardiovascular events in patients with gout. In this cohort study using a claims database, the authors found a similar incidence rate of cardiovascular events in patients with gout under xanthine oxidase inhibitor treatment compared with matched, untreated patients with gout. The authors discussed the potential explanations for this result, such as a short follow-up period (1.4 years), an irregular adherence to the xanthine oxidase inhibitors, or the possibility that there is no causal relationship between gout and cardiovascular disease.
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