BACKGROUND The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA). METHODS We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999-2012) and a commercial health insurance plan (Optum Clinformatics | 2000-2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset. RESULTS The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75-1.10) in Medicaid and 0.88 (0.61-1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54-0.93] and 1.16 [0.89-1.52] in men and women respectively, interaction term p-value = 0.01). CONCLUSIONS Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.

中文翻译：

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罗格列酮与吡格列酮的心脏骤停和室性心律失常的风险：噻唑烷二酮安全性的真实世界证据。

背景技术噻唑烷二酮类药物的低成本使其成为全球超过 3 亿经济困难的 2 型糖尿病患者的潜在有价值的治疗选择。噻唑烷二酮类对心肌中过氧化物酶体增殖物激活受体的不同选择性可能导致不同的致心律失常作用。我们研究了噻唑烷二酮类药物对门诊心脏骤停 (SCA) 和室性心律失常 (VA) 的实际影响。方法 我们在五个医疗补助计划（加利福尼亚州、佛罗里达州、纽约州、俄亥俄州、宾夕法尼亚州 | 1999-2012）和商业健康保险计划（Optum Clinformatics | 2000-2016）中进行了基于人群的高维倾向评分匹配队列研究。我们根据罗格列酮或吡格列酮配药事件来定义暴露；后者充当主动比较器。我们通过在倾向评分上匹配暴露组来控制混杂，通过数据自适应方法识别的基线协变量提供信息。我们使用经过验证的、基于诊断的算法确定了 SCA/VA 结果，从而促进了医院就诊。我们通过 Cox 比例风险回归生成边际风险比 (HR)，该回归解释了匹配对内的聚类。我们预先指定 Medicaid 和 Optum 结果分别为主要和次要；后者作为概念复制数据集。结果 罗格列酮（与吡格列酮）使用者的 SCA/VA 调整后 HR 在 Medicaid 中为 0.91 (0.75-1.10)，在 Optum 中为 0.88 (0.61-1.28)。在 Medicaid 参与者中，但在 Optum 参与者中，我们发现不同性别的治疗效果存在异质性（男性和女性的调整后 HR 分别 = 0.71 [0.54-0.93] 和 1.16 [0.89-1.52]，交互作用项 p 值 = 0.01）。结论 罗格列酮和吡格列酮似乎与类似的 SCA/VA 风险相关。