- In a 10-year observational study of patients with gout, dose escalation during the first 2 years of therapy with allopurinol (eg, Zyloprim), a urate-lowering drug, was unexpectedly associated with a small (<10%) increase in all-cause mortality.
Why this matters
- Clinicians should use a static dosing strategy during the initial 2 years of therapy.
- Mortality outcomes were compared among 6428 dose escalators and 6428 matched nonescalators.
- Patients were propensity-matched to reduce the effect of potential confounders like disease severity.
- Dose escalators were defined as having a higher final average daily dose within the first 2 years of therapy than their initial daily dose.
- Funding: Rheumatology Research Foundation; University of Nebraska Medical Center; Nebraska Arthritis Outcomes Research Center.
- The overall death rate among allopurinol escalators and nonescalators was 40.4 deaths per 1000 person-years.
- Dose escalators had higher all-cause mortality than nonescalators (HR, 1.08; 95% CI, 1.01-1.17).
- Dose escalators had nonsignificantly higher cardiovascular mortality (HR, 1.08; 95% CI, 0.97-1.21) and cancer mortality (HR, 1.06; 95% CI, 0.88-1.27) than nonescalators.
- Observational design.