Impact of changes in serum uric acid levels on clinical outcomes in patients with asymptomatic hyperuricemia

Abstract Background Hyperuricemia is associated with gout and several pathological conditions, including cardiovascular, kidney, and metabolic diseases. However, many individuals with hyperuricemia remain asymptomatic. This study evaluated the impact of serum uric acid (SUA) reduction following urate-lowering therapy on subsequent outcomes in patients with asymptomatic hyperuricemia. Methods This study is a post hoc analysis of Febuxostat for Cerebral and CaRdiovascular Events PrEvEntion StuDy (FREED), a randomized controlled trial. Patients were divided into two groups based on the change in SUA levels between study enrollment and six months. A reduction of 2.0 mg/dL was used as the cut-off point to compare the subsequent outcome events. The primary outcome was a composite of cerebral, cardiovascular, and renal events, as well as all-cause mortality. Results In total, 974 (91.0%) of the 1,070 patients from the original FREED trial were included. At baseline, the mean SUA level was 7.52 ± 1.03 mg/dL, which decreased to 5.67 ± 1.88 mg/dL at six months. Of the patients, 461 (47.3%) achieved SUA reduction ≥2.0 mg/dL (mean 4.35 ± 1.42 mg/dL), while 513 (52.7%) had <2.0 mg/dL reduction (mean 6.87 ± 1.42 mg/dL). No significant reduction in the primary composite outcome was observed with SUA reduction ≥2.0 mg/dL (hazard ratio 1.274; 95% confidence interval 0.907–1.790; P = 0.1623). Conclusion In patients with asymptomatic hyperuricemia, a large reduction in SUA levels at 6 months following urate-lowering therapy did not result in a decrease in subsequent outcome events. Treatment strategies for this population require careful consideration.