Abstract
BackgroundThe purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults.MethodsIn 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.ResultsCrude 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).ConclusionsA 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.
Highlights
The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults
Patient characteristics and crude rates in patients receiving allopurinol or febuxostat We found 42,704 new allopurinol or febuxostat treatment episodes in 35,030 patients, and 2591 of these episodes ended in incident dementia (Fig. 1)
Propensity-matched analysis of allopurinol or febuxostat use: risk of dementia Most of the significant differences noted between allopurinol and febuxostat users before propensity matching (Additional file 1) were eliminated and reduced to Incident dementia* during the follow-up
Summary
The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults. The association of uric acid levels and dementia is an emerging area of interest. An important unanswered question is whether urate-lowering therapy (ULT) use affects the risk of dementia. We recently showed that, compared with non-use, use allopurinol or febuxostat (the most commonly used ULTs) was not associated with any increase in the risk of dementia in older adults [1]. Allopurinol or febuxostat potentially reduces the risk of dementia by inhibiting XOR and reducing uric acid production; given its non-selective inhibition of other purine and pyrimidine pathways, allopurinol may differ in effect from febuxostat [2]
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