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Allopurinol Dose Escalation and Mortality Among Patients With Gout
Author(s) -
Coburn Brian W.,
Michaud Kaleb,
Bergman Debra A.,
Mikuls Ted R.
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40486
Subject(s) - allopurinol , medicine , gout , hazard ratio , hyperuricemia , confidence interval , proportional hazards model , propensity score matching , observational study , incidence (geometry) , uric acid , physics , optics
Objective Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause‐specific mortality in patients with gout. Methods In this 10‐year observational, active‐comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause‐specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non‐escalators) over a 2‐year period. Results Among the 6,428 dose escalators and 6,428 matched non‐escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person‐years). Dose escalators experienced an increase in all‐cause mortality (hazard ratio [ HR ] 1.08, 95% confidence interval [95% CI ] 1.01–1.17), with the effect sizes being similar for incidence of cardiovascular‐related deaths ( HR 1.08, 95% CI 0.97–1.21) and cancer‐related deaths ( HR 1.06, 95% CI 0.88–1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate ( SU ) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular‐related mortality ( HR 0.93, 95% CI 0.76–1.14). Conclusion This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active‐comparator design. Dose escalation was associated with a small (<10%) increase in all‐cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real‐life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.