DOES TREATMENT OF ASYMPTOMATIC HYPERURICEMIA IMPROVE HEALTH OUTCOMES? A DECISION- ANALYTIC EVALUATION

Purpose:    Recent studies suggest that elevated serum uric acid is associated with increased risk for coronary and cerebrovascular disease.  Treatment with urate lowering drugs like Allopurinol may reduce cardiovascular events. The purpose of this study was to examine quality-of-life benefits and risks of treating asymptomatic hyperuricemia with Allopurinol.

Method:    A Markov state-transition model was constructed to assess the occurrence of cardiovascular and neurovascular events and to estimate life expectancy in patients undergoing urate-lowering treatment with Allopurinol.     The model simulated three hypothetical cohorts of male patients 50-years and older having asymptomatic hyperuricemia, each with different serum urate concentrations (4-5.9mg/dl, 6-6.9mg/dl and 7-7.9mg/dl). Age-specific incidences of gout, cardio- and neurovascular events were modeled across different serum urate concentrations. Sensitivity analyses were conducted for probability of adverse drug reactions, incidence of gout, incidence and death from a vascular event. Probabilities and quality adjustment values were obtained from published literature. Life expectancy was derived from Centers for Disease Control and Prevention Life Tables 2005. The outcome measure was quality-adjusted life expectancy (QALE). 

Result:  

	Serum Urate (mg/dl)
Decision	4 - 5.9 mg/dl	6 - 6.9 mg/dl	7 - 7.9mg/dl
Treat (QALYS)	31.837	31.190	30.749
Don't Treat (QALYS)	32.152	31.162	30.201

   A serum urate level > 7mg/dl favored treatment and yielded the maximum gain in QALYs compared to watchful waiting at 0.55 QALYs or 6.6 months.     Sensitivity analysis showed treatment with Allopurinol was well tolerated at drug reaction rates up to 27% (6-6.9mg/dl) and 84% (7-7.9mg/dl). Treatment strategy was most effective in preventing incidence and death from vascular events at higher serum urate.

Conclusion:    Allopurinol treatment was more effective than watchful waiting for patients with asymptomatic hyperuricemia at serum urate concentrations above 6mg/dl based on QALE.  Treatment proved to be protective against long-term cardiovascular and neurovascular events, generating a maximum gain in QALY of 6.6 months.  A clinical trial that evaluates long-term effectiveness of treating asymptomatic hyperuricemia with urate lowering therapies in preventing cardio and neurovascular events would prove useful in validating these results.