Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan; Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Internal Medicine, Sakurajyuji Yatsushiro Rehabilitation Hospital, Yatsushiro, Japan.
Int J Cardiol. 2022 Feb 15;349:127-133. doi: 10.1016/j.ijcard.2021.11.076. Epub 2021 Dec 3.
We previously reported on the FREED study, which found that febuxostat reduced the risk of adverse clinical outcome in patients with asymptomatic hyperuricemia without gout. We have now investigated outcomes in subgroups of FREED patients with and without a history of cardiovascular disease (CVD).
We performed a post hoc subgroup analysis of 1070 patients randomized to the febuxostat or non-febuxostat group and followed for 36 months.
At baseline, 234 patients (21.9%) had a history of CVD, including 86 patients with stroke (36.8%), 90 with coronary artery disease (38.5%), 74 with heart failure (31.6%), and 25 with vascular disease (10.7%). The risk for the primary composite endpoint, i.e., cerebral, cardiovascular, and renal events and all deaths, was higher in patients with CVD than in those without CVD (34.2% vs 23.7%; p < 0.001). Treatment with febuxostat lowered rates of the primary composite endpoint in patients with CVD (hazard ratio [HR] 0.601, 95% CI 0.384 to 0.940, p = 0.026), and these effects were consistently observed in subgroups with and without CVD (p = 0.227 for treatment by subgroup interaction). Furthermore, in the subgroup with CVD, all-cause mortality was significantly lower in the febuxostat group than in the non-febuxostat group (HR 0.160, 95% CI 0.047 to 0.547, p = 0.004), with a significant subgroup interaction (p = 0.007 for treatment by subgroup interaction).
In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of the composite of cerebral, cardiovascular, and renal events and death in the secondary prevention setting.
我们之前报告了 FREED 研究的结果，该研究发现非布司他可降低无症状高尿酸血症患者发生不良临床结局的风险，这些患者不伴有痛风。现在，我们调查了 FREED 患者亚组（伴有和不伴有心血管疾病病史）的结局。
我们对 1070 例随机分配至非布司他组或非非布司他组的患者进行了事后亚组分析，并随访 36 个月。
在基线时，234 例（21.9%）患者有心血管疾病病史，包括 86 例（36.8%）脑卒中、90 例（38.5%）冠心病、74 例（31.6%）心力衰竭和 25 例（10.7%）血管疾病。有心血管疾病病史的患者发生主要复合终点（包括脑、心血管和肾脏事件以及所有死亡）的风险高于无心血管疾病病史的患者（34.2%比 23.7%；p<0.001）。非布司他治疗降低了有心血管疾病病史的患者主要复合终点的发生率（风险比[HR]0.601，95%置信区间[CI]0.384 至 0.940，p=0.026），并且这些效果在有和无心血管疾病病史的亚组中均一致观察到（治疗与亚组间交互作用的 p 值为 0.227）。此外，在有心血管疾病病史的亚组中，非布司他组的全因死亡率显著低于非非布司他组（HR 0.160，95%CI 0.047 至 0.547，p=0.004），并且存在显著的治疗与亚组间交互作用（p=0.007）。
在无症状高尿酸血症不伴有痛风的患者中，非布司他降低了二级预防环境中脑、心血管和肾脏事件及死亡的复合风险。
