Objective: Four clinical studies of dotinurad in patients with hyperuricemia with or without gout conducted in Japan were pooled to evaluate the relationship between the cumulative number of cardiovascular risk factors (obesity, hypertension, dyslipidemia, and impaired glucose tolerance) and the uric acid-lowering effect of dotinurad.
Methods: The full analysis set populations in each study were pooled, of which 421 and 59 patients were administered dotinurad and the placebo, respectively. Dotinurad was evaluated at doses of 0.5, 1, 2, and 4 mg in these studies. Endpoints were the rate of decrease in serum uric acid levels and the rate of achievement of serum uric acid levels ≤ 6.0 mg/dL with the cumulative number of cardiovascular risk factors.
Results: Dotinurad showed serum uric acid-lowering effect in hyperuricemic patients with multiple cardiovascular risk factors. Administering 2 mg dotinurad exhibited a lower rate of achieving serum uric acid levels ≤ 6.0 mg/dL in patients with more cardiovascular risk factors than in those with fewer cardiovascular risk factors. However, serum uric acid levels ≤ 6.0 mg/dL were achieved in almost all patients treated with 4 mg dotinurad regardless of the cumulative number of cardiovascular risk factors.
Conclusion: Dotinurad lowered serum uric acid levels in hyperuricemic patients with multiple cardiovascular risk factors. Adjusting the dose of dotinurad while taking into consideration the patient's background of multiple cardiovascular risk factors may be a new therapeutic strategy to control serum uric acid levels.