Lin Hsiu-Chen, Daimon Masao, Wang Ching-Hung, Ho Yi, Uang Yow-Shieng, Chiang Shuo-Ju, Wang Li-Hsuan
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Department of Clinical Laboratory, Tokyo University Hospital, Tokyo, Japan.
Int J Cardiol. 2017 Apr 15;233:85-90. doi: 10.1016/j.ijcard.2017.02.013. Epub 2017 Feb 13.
The effect of gout on the risk of developing coronary artery disease (CAD) is uncertain. Some studies have found that gout is a risk factor for acute myocardial infarction. This study examined the changes in risk of CAD in gout patients taking allopurinol and/or benzbromarone, and analyzed the dose-response relationship of both drugs with CAD incidence.
The medical records of one million subjects from 2000 to 2011 were provided by the Taiwan National Health Insurance Research Database. Cox proportional hazard ratio was used to compare the risk of CAD in gout patients taking allopurinol or/and benzbromarone with those taking neither drug. Hazard ratios (HR) were adjusted for possible confounding factors, including age, gender, hypertension, hyperlipidemia, diabetes mellitus, chronic kidney disease, and relevant medications.
Of 8047 gout patients, 1422 were treated with allopurinol (Group A), 4141 with benzbromarone (Group B), and 2484 with both drugs (Group A/B) during the follow-up period. Our results showed the incidence of CAD after adjusting for covariates for Group A, Group B, and Group A/B did not significantly differ from the comparison group. However, after adjustment for covariates in dose-response analyses, treatment with over 270 defined daily doses (DDDs) of allopurinol, and over 360 DDDs of benzbromarone, was associated with a significantly reduced risk of CAD.
We found that the use of allopurinol and benzbromarone, whether alone or in combination, had a linear dose-response relationship between the numbers of defined daily doses and the risk of CAD, especially in higher DDDs.
痛风对冠状动脉疾病(CAD)发病风险的影响尚不确定。一些研究发现痛风是急性心肌梗死的危险因素。本研究调查了服用别嘌醇和/或苯溴马隆的痛风患者CAD风险的变化,并分析了这两种药物与CAD发病率之间的剂量反应关系。
台湾全民健康保险研究数据库提供了2000年至2011年100万受试者的医疗记录。采用Cox比例风险比来比较服用别嘌醇或/和苯溴马隆的痛风患者与未服用这两种药物的痛风患者发生CAD的风险。风险比(HR)针对可能的混杂因素进行了调整,包括年龄、性别、高血压、高脂血症、糖尿病、慢性肾脏病及相关药物。
在8047例痛风患者中,随访期间1422例接受别嘌醇治疗(A组),4141例接受苯溴马隆治疗(B组),2484例同时接受两种药物治疗(A/B组)。我们的结果显示,在对协变量进行调整后,A组、B组和A/B组的CAD发病率与对照组相比无显著差异。然而,在剂量反应分析中对协变量进行调整后,服用超过270限定日剂量(DDD)的别嘌醇以及超过360 DDD的苯溴马隆与CAD风险显著降低相关。
我们发现,别嘌醇和苯溴马隆单独使用或联合使用时,限定日剂量数与CAD风险之间存在线性剂量反应关系,尤其是在较高的DDD时。