Yokota Takashi, Kinugawa Shintaro, Fukushima Arata, Okumura Takahiro, Murohara Toyoaki, Tsutsui Hiroyuki
Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Kita-14 Nishi-5, Kita-ku, Sapporo, 060-8648, Japan.
Heart Vessels. 2025 Feb;40(2):111-122. doi: 10.1007/s00380-024-02448-9. Epub 2024 Aug 19.
Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70 years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality.
高尿酸血症是慢性心力衰竭（CHF）患者死亡率的独立预测因素。为了确定降尿酸药物非布司他是否可以改善CHF患者的临床结局，我们开展了一项多中心、前瞻性、随机、开放标签、终点设盲的研究，治疗期为24周。我们将诊断为左心室射血分数降低（LVEF＜40%）且无症状高尿酸血症（血清尿酸[UA]水平＞7.0mg/dl且＜10.0mg/dl）的日本门诊患者随机分为非布司他组（n = 51）或对照组（n = 50）。主要疗效终点是从基线至第24周（或停药时）对数转换后的血浆B型利钠肽（BNP）水平的变化。次要疗效终点是从基线至第24周通过超声心动图评估的左心室收缩或舒张功能、纽约心脏协会（NYHA）分级、血红蛋白和估算肾小球滤过率的变化，以及从基线至第4、8、12、16和20周（BNP）或第4、8、12、16、20和24周（血清UA）对数转换后的血浆BNP水平或血清UA水平的变化。主要安全终点是全因死亡或重大心血管事件的发生。参与者的平均年龄为70岁；14%为女性。尽管非布司他组从基线至第4、8、12、16和20周对数转换后的血浆BNP水平下降幅度更大，但非布司他组和对照组在主要疗效终点方面无差异（p = 0.13）。除了非布司他组血清UA水平降低外，两组在主要安全终点或次要疗效终点方面无显著差异。非布司他在CHF患者第24周时未降低血浆BNP水平，但似乎安全，未增加重大心血管事件以及全因或心血管死亡率。
