Lee Jung Sun, Oh Ji Seon, Kim Yong-Gil, Lee Chang-Keun, Yoo Bin, Hong Seokchan
Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Seoul Veterans Hospital, Seoul, Republic of Korea.
Department of Biomedical Informatics, Asan Medical Center, Seoul, Republic of Korea.
Med Hypotheses. 2020 Aug;141:109740. doi: 10.1016/j.mehy.2020.109740. Epub 2020 Apr 13.
Results from a recent study showed that the risk of cardiovascular and all-cause mortality was higher in patients who received febuxostat, a potent urate-lowering agent, than that in patients who received allopurinol. Therefore, we hypothesized that an abrupt change in serum urate levels caused by urate-lowering agents would influence the risk of cardiovascular events.
We included patients with a history of cardiovascular disease (CVD) who received allopurinol or febuxostat. Cardiovascular events were defined as follows: nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, and cardiovascular death. The change in serum urate levels was determined by the difference or reduction rate in urate within 6 months after exposure to allopurinol or febuxostat. The factors associated with cardiovascular events were evaluated by Cox regression analysis.
In total, 207 patients with CVD who were exposed to allopurinol or febuxostat were included. Cardiovascular events occurred in 38 patients (18.4%). In univariate analysis, age, diabetes mellitus, baseline urate levels, difference in mean urate levels between baseline and post-exposure (Δurate), and reduction rate in urate to the lowest post-exposure levels (Δurate/day) were associated with cardiovascular events. Further, results from the multivariate analysis revealed that age [hazard ratio (HR) 1.036, 95% confidence interval (CI), 1.001-1.072, p = 0.042], Δurate (HR 1.188, CI, 1.033-1.366, p = 0.015), and Δurate/day (HR 6.963, CI, 2.215-21.886, p = 0.001) were associated with cardiovascular events.
Rapid reduction in serum urate levels was associated with a higher risk of cardiovascular events. Thus, careful attention should be paid to abruptly changing serum urate levels after treating urate-lowering agent in high-risk CVD patients.
最近一项研究的结果显示，接受强效降尿酸药物非布司他的患者发生心血管疾病及全因死亡的风险高于接受别嘌醇的患者。因此，我们推测降尿酸药物引起的血清尿酸水平突然变化会影响心血管事件的风险。
我们纳入了接受别嘌醇或非布司他治疗且有心血管疾病（CVD）病史的患者。心血管事件定义如下：非致死性心肌梗死、非致死性中风、不稳定型心绞痛、心力衰竭和心血管死亡。血清尿酸水平的变化通过接触别嘌醇或非布司他后6个月内尿酸的差值或降低率来确定。通过Cox回归分析评估与心血管事件相关的因素。
总共纳入了207例接触别嘌醇或非布司他的CVD患者。38例患者（18.4%）发生了心血管事件。单因素分析中，年龄、糖尿病、基线尿酸水平、基线与接触后平均尿酸水平的差值（Δ尿酸）以及尿酸降至接触后最低水平的降低率（Δ尿酸/天）与心血管事件相关。此外，多因素分析结果显示，年龄[风险比（HR）1.036，95%置信区间（CI），1.001 - 1.072，p = 0.042]、Δ尿酸（HR 1.188，CI，1.033 - 1.366，p = 0.015）和Δ尿酸/天（HR 6.963，CI，2.215 - 21.886，p = 0.001）与心血管事件相关。
血清尿酸水平的快速降低与心血管事件的较高风险相关。因此，在高危CVD患者中使用降尿酸药物治疗后，应密切关注血清尿酸水平的突然变化。
