Treatment of Asymptomatic Hyperuricemia and Prevention of Vascular Disease: A Decision Analytic Approach

Abstract

Objective.Elevated serum urate may be associated with an increase in cardiovascular (CV) disease. Treating asymptomatic hyperuricemia with urate-lowering drugs such as allopurinol may reduce CV events. We designed a model to simulate the effect of allopurinol treatment on reducing frequency of CV events in individuals with elevated serum urate.Methods.A Markov state-transition model was constructed to assess occurrence of vascular events (VE) for 2 treatment strategies: treat all asymptomatic individuals with allopurinol (Treat All) and treat only if symptomatic (Treat Symptomatic). The model simulated a hypothetical cohort of 50-year-old men with different serum urate concentrations (6–6.9 and 7–7.9 mg/dl) followed over 20 years. Age and sex subgroups were analyzed. Model inputs were derived from current literature. The main outcome measures were mean number of VE and mean number of deaths from VE.Results.For 50-year-old men with serum urate 6.0–6.9 mg/dl, individuals in the Treat All strategy have a 30% reduction in the mean number of VE compared to those in the Treat Symptomatic strategy (mean VE: 0.078 vs 0.11), and a 39% reduction in mean number of deaths from VE. At higher serum urate concentrations, treatment is more effective in reducing the mean number of VE and mean number of deaths from VE (38% event, 54% death). Results for women show similar trends. As the cohort ages, treatment has less effect on reducing VE. The number needed to treat to prevent 1 event is 20 (men, 7.0–7.9 mg/dl).Conclusion.The model predicts that treating asymptomatic hyperuricemia with allopurinol is most effective in preventing VE at a serum urate above 7.0 mg/dl in men and 5.0 mg/dl in women.