Re: To Treat or Not to Treat? Effect of Urate-Lowering Therapy on Renal Function, Blood Pressure and Safety in Patients with Asymptomatic Hyperuricemia

To the Editor: Tien et al conducted a network meta-analysis to investigate the effects of different urate-lowering therapies on serum uric acid level, renal function, blood pressure, and safety in patients with asymptomatic hyperuricemia.¹ Regarding safety information, allopurinol had an advantage of reno-protective effect, and febuxostat had a significant impact in lowering diastolic blood pressure. I present additional information on the safety of urate-lowering therapies. Gao et al conducted a meta-analysis to summarize the cardiovascular safety of febuxostat for the treatment of gout,² and the pooled odds ratios (95% confidence intervals [CI]) of febuxostat compared with allopurinol for the composite of urgent coronary revascularization and stroke were 0.84 (95% CI: 0.77–0.90) and 0.87 (95% CI: 0.79–0.97). I think that there is an advantage to avoiding cardiovascular side effects by using febuxostat instead of allopurinol. Tien et al handled patients with asymptomatic hyperuricemia, which may relate to the safety of urate-lowering therapies. By the way, there are 2 important clinical trials to compare the safety of allopurinol and febuxostat: “CARES trial” and “FAST trial.”^3,4 Choi et al precisely compared 2 studies and concluded that “FAST trial” can be accepted by keeping internal consistency with high rates of follow-up.⁵ Fundamentally, there are big differences in the cardiovascular disease (CVD) comorbidities of the target gout patients in 2 trials. Patients with major CVDs within the past 6 months at baseline were excluded in the “FAST trial,” and the same exclusion was conducted within the past 60 days at baseline in “CARES trial.” Both trials present important information regarding the safety of gout pharmacotherapy, respectively. I think that mortality risk in gout patients with severe CVDs should be conferred to outcomes from “CARES trial,” although internal inconsistency exists. In contrast, mortality risk in gout patients with mild-to-moderate CVDs should be conferred to outcomes from the “FAST trial.” As there is limited information regarding the safety of urate-lowering therapies in patients with asymptomatic hyperuricemia, more randomized controlled trials should be conducted to specify the risk of pharmacotherapy with special reference to asymptomatic hyperuricemia.