Comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults: a propensity-matched analysis.
Level 3 - non-randomized controlled study
Propensity score-matched retrospective cohort study using administrative claims data
PubMed 30075731 · doi:10.1186/s13075-018-1663-3
What was done
A retrospective cohort study using Medicare claims data evaluated older adults newly initiated on allopurinol or febuxostat following a 365-day baseline period without either drug. Investigators used 5:1 propensity score-matched Cox regression models to calculate hazard ratios (HR) of incident dementia, comparing febuxostat to allopurinol as well as examining drug dose and treatment duration.
What was found
Crude dementia rates per 100,000 person-days were 12 (<200 mg/day), 9 (200–299 mg/day), and 8 (≥300 mg/day) for allopurinol, and 9 (40 mg/day) and 8 (80 mg/day) for febuxostat. In propensity-matched analyses, febuxostat use was not significantly different from allopurinol use overall (HR 0.79, 95% CI 0.61–1.03). Compared to allopurinol <200 mg/day, lower dementia hazards were observed with allopurinol 200–299 mg/day (HR 0.80, 95% CI 0.64–0.98), allopurinol ≥300 mg/day (HR 0.59, 95% CI 0.50–0.71), and febuxostat 40 mg/day (HR 0.64, 95% CI 0.47–0.86). Duration of therapy (compared to 1–180 days of allopurinol) was not significantly associated with dementia risk (HR range 0.76–1.14).
Why it matters
This study provides comparative real-world evidence on xanthine oxidase inhibitors, suggesting a potential dose-dependent inverse association between urate-lowering therapy dose and incident dementia risk in older adults.
Limits
The total sample size was not reported in the abstract. The study relies on administrative Medicare claims data, which is subject to diagnostic misclassification of dementia, lack of clinical cognitive measures, unmeasured confounding, and inability to verify actual medication adherence.
Cited by
- supports A study from the University of Alabama by Dr. Singh showed that uric acid-lowering drugs like allopurinol protect against Alzheimer's disease in a dose-dependent manner.