Comparative cardiovascular risk of allopurinol versus febuxostat in patients with gout: a nation-wide cohort study

Objective To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat. Methods Using 2002–2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths. Results We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person-years for the primary outcome was 1.89 for allopurinol and 1.84 for febuxostat initiators. The corresponding hazard ratio comparing allopurinol vs febuxostat initiators was 1.09 (95% CI: 0.90, 1.32). No significant difference was found for the secondary outcomes, including all-cause mortality (hazard ratio 0.96; 95% CI: 0.79, 1.16). Subgroup analyses limited to those at high CV risk and to equipotent-dose initiators (i.e. allopurinol ⩾300 mg/day vs febuxostat ⩾40 mg/day) showed similar results. Conclusion Overall, this large Korean population-based study suggests no difference in the risk of non-fatal CV events and all-cause mortality between allopurinol and febuxostat initiators. These findings are consistent with the recent US Medicare population study, although the current study population consisted of younger Asians.