Background/Purpose: Gout, a disorder of uric acid deposition, is commonly treated with xanthine oxidase inhibitors like febuxostat and allopurinol.  While it is well-known that patients with gout are at increased risk of cardiovascular (CV) disease, little evidence is available with regard to comparative CV safety of febuxostat and allopurinol in the general older population.

Methods: Using claims data from U.S. Medicare (2008-2013), we conducted a cohort study among gout patients aged ≥65 initiating febuxostat versus allopurinol. All patients were continuously enrolled in Medicare parts A/B/D for ≥1 year free of a given drug prior to the 1^st dispensing date (index date). The primary outcome was a composite CV endpoint of myocardial infarction (MI) or stroke.  Secondary outcomes comprised MI, stroke, coronary revascularization, and new and recurrent heart failure (HF) requiring hospitalization.  Follow-up time began the day after index date to the earliest day of the following: drug discontinuation, insurance disenrollment, occurrence of outcome, death, nursing home admission or last day of the study period. To adjust for ≥55 baseline covariates and index year, we used propensity score (PS) matching with a 1:3 ratio. Cox proportional hazards regression compared the risk of primary and secondary outcomes in the PS-matched cohorts of febuxostat and allopurinol initiators.

Results: We included 24,900 febuxostat initiators PS-matched on 74,700 allopurinol initiators.  The median age was 76 years, 52% were male, and 32% had CV disease at baseline. During the mean (SD) follow-up time of 1.1 (1.1) years among febuxostat initiators and 1.2 (1.2) years among allopurinol initiators, the incidence rate (IR) per 100 person-years for the primary endpoint (MI or stroke) was 3.45 (95% CI, 3.24-3.68) in febuxostat and 3.34 (95% CI, 3.23-3.46) in allopurinol initiators.  Hazard ratios (HR) for MI or stroke were 1.02 (95% CI, 0.95-1.10) in the febuxostat versus allopurinol groups. The risk of developing secondary outcomes was also similar in both groups (Table).  For new-onset HF hospitalization, the IR in the febuxostat group was 5.72 (95% CI, 5.39-6.08) per 100 person-years with a HR of 1.04 (95% CI, 0.97-1.12) compared to allopurinol.  Among patients with baseline HF, the IR of first-time HF exacerbation was 42.66 (95% CI, 41.12-44.26) per 100 person-years among febuxostat initiators with a HR of 0.95 (95% CI, 0.91-0.99) versus allopurinol.

Conclusion: Among 99,600 older patients with gout enrolled in Medicare, there was no difference in CV risk (including MI, stroke, coronary revascularization and new/recurrent HF) between patients initiating febuxostat compared to allopurinol.