Risk of Stroke with Thiazolidinediones: A Ten-Year Nationwide Population-Based Cohort Study
Risk of Stroke with Thiazolidinediones: A Ten-Year Nationwide Population-Based Cohort Study
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DOI：
10.1159/000353679
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Hsu, Chung Y.
中科院分区：
文献类型：
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作者：
Lu, Chien-Jung;Sun, Yu;Hsu, Chung Y.
背景：噻唑烷二酮(TZDS)-罗格列酮和吡格列酮是一类用于治疗2型糖尿病的胰岛素增敏剂，临床前研究表明具有神经保护作用，对糖尿病合并胰岛素抵抗的患者有良好的血糖控制效果。然而，临床试验和观察性研究提高了接受罗格列酮治疗的患者中风风险增加的可能性。吡格列酮是否具有类似的中风风险仍不确定。大多数关于TZDS对心血管影响的研究都是基于美国和欧洲的研究。本研究旨在比较亚洲人群中服用TZD和非TZD药物的糖尿病患者的中风风险。方法：研究队列包括15,981名被诊断为糖尿病且无中风、急性心肌梗死(AMI)或心力衰竭的患者，他们在2001-2010年间接受了跟踪调查。患者按处方分为罗格列酮组、吡格列酮组和非TZD组。研究终点包括缺血性中风和出血性中风。鉴于罗格列酮与心力衰竭和急性心肌梗死有关联的报道，这两个终点也包括在本研究中。用COX风险比例模型估计发生终点的风险。用似然比检验年龄与药物的相互作用。通过比较不同累积暴露于TZD的患者的发病率来评估剂量-反应效应。结果：10年随访期间，罗格列酮组发生缺血性卒中(多变量调整风险比，HR=1.39；95%可信区间，CI=1.16~1.66)和心力衰竭(HR=1.59，95%CI=1.18~2.14)的风险显著高于非TZD组。在缺血性卒中(HR=0.97；95%CI=0.75~1.26)和心力衰竭(HR=0.94；95%CI=0.59~1.50)方面，吡格列酮组与非TZD组差异无统计学意义。结果还显示，随着罗格列酮剂量的增加，缺血性中风的风险增加具有显著的剂量依赖关系，而在任何水平的吡格列酮剂量下，风险都没有增加。结论：这项基于人群的队列研究表明，罗格列酮在这一亚洲患者群体中增加了发生中风或心力衰竭的风险，这表明罗格列酮的不良副作用跨越了种族界限。另一方面，在没有大血管病史的糖尿病患者中，与非TZD组相比，吡格列酮不会增加心血管或中风的风险。版权所有(C)2013年，S.Karger AG，巴塞尔
Background: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. Methods: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. Results: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. Conclusions: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease. Copyright (c) 2013 S. Karger AG, Basel