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

Rheumatology (Oxford). 2019 Dec 1;58(12):2122-2129. doi: 10.1093/rheumatology/kez189.

Abstract

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.

Keywords: allopurinol; cardiovascular disease; febuxostat; gout.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Allopurinol / therapeutic use*
  • Cardiovascular Diseases / epidemiology*
  • Cohort Studies
  • Febuxostat / therapeutic use*
  • Female
  • Gout / drug therapy*
  • Gout Suppressants / therapeutic use*
  • Humans
  • Ischemic Attack, Transient / epidemiology
  • Male
  • Middle Aged
  • Mortality
  • Myocardial Infarction / epidemiology
  • Myocardial Revascularization / statistics & numerical data
  • Proportional Hazards Models
  • Republic of Korea / epidemiology
  • Stroke / epidemiology

Substances

  • Gout Suppressants
  • Febuxostat
  • Allopurinol