Kawachi Yusuke, Fujishima Yuya, Nishizawa Hitoshi, Tanaka Atsushi, Yoshida Hisako, Niwano Shinichi, Suzuki Makoto, Shimomura Iichiro, Node Koichi
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University.
Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University.
J Atheroscler Thromb. 2025 Apr 1;32(4):474-490. doi: 10.5551/jat.65087. Epub 2024 Oct 3.
The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function.
The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months.
Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, -0.41 [95% CI, -1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, -1.12 [95% CI, -2.23 to -0.01]; p=0.048 for ALT ≥ 30 U/L and -1.08 [95% CI, -2.13 to -0.03]; p=0.044 for AST ≥ 30 U/L).
Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.
黄嘌呤氧化还原酶（XOR）抑制剂降低尿酸（UA）治疗对心血管疾病发展的影响有待进一步研究。本研究旨在评估非布司他对动脉僵硬度的长期影响，重点关注肝功能。
PRIZE研究将无症状高尿酸血症患者随机分为两组，分别接受非布司他附加治疗（非布司他组）或非药物治疗（对照组）。在514名参与者中，非布司他组和对照组分别有23名和14名患者使用心踝血管指数（CAVI）评估动脉僵硬度。每组参与者再根据其基线丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）水平（高于或低于中位数或30 U/L）进一步分组。主要终点是从基线到12个月和24个月时CAVI的变化。
总体而言，对照组和非布司他组在24个月时CAVI变化的最小二乘均值估计中未发现显著差异（组间平均差异为-0.41 [95% CI，-1.05至0.23]；p = 0.204）。然而，在24个月时基线ALT或AST水平高于30 U/L的参与者中存在显著差异（组间平均差异为-1.12 [95% CI，-2.23至-0.01]；ALT≥30 U/L时p = 0.048，AST≥30 U/L时为-1.08 [95% CI，-2.13至-0.03]；p = 0.044）。
非布司他两年治疗对高尿酸血症和肝功能不全患者的CAVI有有益影响。
