No Difference in CV Risk in Gout Treated With Allopurinol vs Febuxostat

Uric acid crystal
Uric acid crystal
Findings showed no difference in the risk of non-fatal cardiovascular outcomes and all-cause mortality between allopurinol and febuxostat treatment in patients with gout.

Consistent with a recent US Medicare population study, a large Korean population-based study with younger participants found no difference in the risk for nonfatal cardiovascular events and all-cause mortality for patients with gout initiating allopurinol compared with febuxostat. Findings from the study were recently published in Rheumatology.

This large, Korean population-based study using Korean National Health Insurance Service data from 2002 to 2015 compared the cardiovascular risk among patients with gout initiating allopurinol vs febuxostat. The primary study outcome was a composite cardiovascular end point of coronary revascularization, myocardial infarction, or stroke/transient ischemic attack. Secondary study outcomes were individual cardiovascular components and all-cause mortality.

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To control for confounding, propensity score matching for allopurinol and febuxostat initiators were used with a 4:1 ratio. To determine whether cardiovascular end points or death occurred after discontinuation of treatment, sensitivity analyses with a 90-day grace period were conducted after the last date of drug availability, and as-treated analyses for all nonfatal cardiovascular and mortality outcomes were performed.

Study included 39,640 allopurinol initiators and 9910 propensity-score-matched febuxostat initiators (mean age 59.1 years old; 78.4% men). The per 100 person-years incidence rate for the primary outcome was 1.89 for allopurinol initiators and 1.84 for febuxostat initiators. Comparing allopurinol with febuxostat initiators, the corresponding hazard ratio was 1.09 (95% CI, 0.90-1.32).

For the secondary outcomes, no significant differences were found, including all-cause mortality (hazard ratio [HR], 0.96; 95% CI, 0.79-1.16), and similar results were found via subgroup analyses limited to participants at high cardiovascular risk and to equipotent-dose initiators (ie, allopurinol ≥300 mg/day vs febuxostat ≥40 mg/day), with an HR of 0.92 for the primary outcome (95% CI, 0.74-1.14) and of 0.83 for all-cause mortality (95% CI, 0.66-1.04).

Study investigators concluded that “we found no difference in the risk for [myocardial infarction), stroke/[transient ischemic attack], coronary revascularization, or all-cause mortality. These findings replicate the recent US Medicare population study. As the study population was composed of younger Asians, these findings add to the generalizability of these findings.”


Kang EH, Choi HK, Shin A, et al. Comparative cardiovascular risk of allopurinol versus febuxostat in patients with gout: a nation-wide cohort study [published online May 16, 2019]. Rheumatology (Oxford). doi:10.1093/rheumatology/kez189