Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Does Treatment of Asymptomatic Hyperuricemia Improve Cardio and Neurovascular Outcomes? A Decision-Analytic Evaluation.

Akkineni1,  Roopa, Lee2,  Alexandra, Miller3,  Katherine L., Tosteson4,  Anna N A., Choi5,  Hyon K., Zhu5,  Yanyan, Albert1,  Daniel A.

Dartmouth-Hitchcock Medical Center, Lebanon, NH
Veterans Affairs National Center for Patient Safety, White River Junction, VT
Northeastern Ohio Universities College of Medicine, Rootstown, OH
Dartmouth Medical School, Lebanon, NH
Boston University School of Medicine, Boston, MA

Background/Purpose:

Recent studies suggest that elevated serum uric acid level is associated with increase in coronary and cerebrovascular disease. Treatment for asymptomatic hyperuricemia with urate lowering drugs like Allopurinol may reduce vascular events. However, some patients have experienced adverse drug reactions when treated with Allopurinol. A decision analysis was designed to identify the optimal treatment strategy for patients with asymptomatic hyperuricemia.

Methods:

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. Number needed to treat (NNT), number needed to harm (NNH) and hypothetical trial sample size calculations were performed.

Results:

 Serum Urate (mg/dl)
Decision4–5.9 mg/dl6–6.9 mg/dl7–7.9mg/dl
Treat (QALYS)31.83731.19030.749
Don't Treat (QALYS)32.15231.16230.201

A serum urate level greater than 7mg/dl favored treatment and yielded the maximum gain in quality-adjusted-life-years [QALYs] compared to watchful waiting at 0.55 QALYs or 6.6 months.

Sensitivity analysis showed treatment with Allopurinol was favored even with drug reaction rates up to 27% (6–6.9mg/dl) and 84% (7–7.9mg/dl). Treatment strategy was most effective at higher serum urate levels in preventing incidence and death from vascular events.

The NNT to prevent one stroke and one fatality from myocardial infarction were 170 and 141 patients respectively. Treatment of 250 patients with Allopurinol would result in one case of Allopurinol hypersensitivity syndrome. A hypothetical trial of Allopurinol treatment versus placebo would involve 2,291 individuals with a serum urate level greater than or equal to 7.0mg/dl followed for one year in order to validate the prevention of cardio and neurovascular events.

Conclusion:

Treatment with Allopurinol was an effective strategy for patients with asymptomatic hyperuricemia at serum urate concentrations above 6mg/dl based on QALY comparison with watchful waiting. Based on the results of our sample size calculation, a clinical trial evaluating the effectiveness of Allopurinol treatment to prevent cardio and neurovascular events in individuals with asymptomatic hyperuricemia would be both feasible and useful in validating these results.

To cite this abstract, please use the following information:
Akkineni, Roopa, Lee, Alexandra, Miller, Katherine L., Tosteson, Anna N A., Choi, Hyon K., Zhu, Yanyan, et al; Does Treatment of Asymptomatic Hyperuricemia Improve Cardio and Neurovascular Outcomes? A Decision-Analytic Evaluation. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1603
DOI:

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