The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults.
In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 365 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident dementia with allopurinol versus febuxostat use and with allopurinol/febuxostat dose and duration.
Crude rates of incident dementia per 100,000 person-days were lower with higher daily dose: allopurinol less than 200, 200 to 299, and at least 300 mg/day with 12, 9, and 8 and febuxostat 40 and 80 mg/day with 9 and 8, respectively. In propensity-matched analyses, compared with allopurinol use, febuxostat use was not significantly different, and the HR of incident dementia was 0.79 (95% confidence interval (CI) 0.61, 1.03). Compared with allopurinol less than 200 mg/day, higher allopurinol doses (200 to 299 and at least 300 mg/day) and the febuxostat 40 mg/day dose were each associated with lower HRs of dementia: 0.80 (95% CI 0.64, 0.98), 0.59 (95% CI 0.50, 0.71), and 0.64 (95% CI 0.47, 0.86), respectively. Compared with allopurinol use for 1 to 180 days, longer allopurinol or febuxostat use durations were not significantly associated with differences in HR of dementia (range of 0.76 to 1.14).
A dose-related reduction in the risk of dementia in older adults was noted with higher allopurinol dose and with febuxostat 40 mg daily dose. Future studies need to examine the mechanism of this benefit.