ABSTRACT

Background: Hyperuricemia is a risk factor for the development of hypertension and is comorbid in many hypertensive patients. According to Japanese hypertension management guidelines published in 2019, a target serum uric acid level of ≤6.0 mg/dL is recommended in hypertensive patients with gout or asymptomatic hyperuricemia. Dotinurad is a novel uric acid-lowering drug classified as a selective urate reabsorption inhibitor. A pooled analysis was performed on the uric acid-lowering effect of dotinurad in 222 hypertensive patients with gout or asymptomatic hyperuricemia in four clinical trials (NCT02344862, NCT02416167, NCT03100318, NCT03372200). Moreover, we analyzed the long-term uric acid-lowering effect of dotinurad in 154 hypertensive patients with gout or asymptomatic hyperuricemia (NCT03006445).

Results: In the pooled analysis, the percent change in the decrease of serum uric acid with the use of dotinurad was 42.17 ± 12.42% at a dose of 2 mg and 60.42 ± 8.03% at a dose of 4 mg; the percentage of patients who achieved a serum uric acid level of ≤6.0 mg/dL was 82.8% and 100.0%. The long-term uric acid-lowering effect of dotinurad showed almost the same results. In this study, the concomitant use of diuretics or angiotensin II receptor blockers affected the uric acid-lowering effect of dotinurad at only a dose of 2 mg in the pooled analysis.

Conclusions: In the pooled analysis, dotinurad lowered serum uric acid levels. Dotinurad has an achievement rate of over 80% for serum uric acid level of ≤6.0 mg/dL in both analyses, and will be clinically useful for the management of hyperuricemic states in hypertensive patients.

摘要

背景：高尿酸血症是高血压发展的危险因素，并且在许多高血压患者中是共病的。根据 2019 年发布的日本高血压管理指南，对于痛风或无症状高尿酸血症的高血压患者，推荐目标血尿酸水平≤6.0 mg/dL。Dotinurad 是一种新型降尿酸药物，属于选择性尿酸重吸收抑制剂。在四项临床试验（NCT02344862、NCT02416167、NCT03100318、NCT03372200）中，对多替瑞德对222名患有痛风或无症状高尿酸血症的高血压患者的降尿酸作用进行了汇总分析。此外，我们分析了 dotinurad 在 154 名患有痛风或无症状高尿酸血症的高血压患者中的长期降尿酸作用 (NCT03006445)。

结果：在汇总分析中，使用多替拉德的血清尿酸降低百分比变化在 2 mg 剂量下为 42.17 ± 12.42%，在 4 mg 剂量下为 60.42 ± 8.03%；血清尿酸水平≤6.0mg/dL的患者百分比分别为82.8%和100.0%。dotinurad的长期降尿酸作用显示出几乎相同的结果。在这项研究中，合并分析中，同时使用利尿剂或血管紧张素 II 受体阻滞剂影响了 dotinurad 的降尿酸作用，剂量仅为 2 mg。

结论：在汇总分析中，dotinurad 降低了血清尿酸水平。在两项分析中，Dotinurad 的血清尿酸水平≤6.0 mg/dL 的实现率超过 80%，并将在临床上用于管理高血压患者的高尿酸血症状态。