Using Real-World Data to Predict Findings of an Ongoing Phase IV Cardiovascular Outcome Trial: Cardiovascular Safety of Linagliptin Versus Glimepiride
Using Real-World Data to Predict Findings of an Ongoing Phase IV Cardiovascular Outcome Trial: Cardiovascular Safety of Linagliptin Versus Glimepiride
复制标题
DOI：
10.2337/dc19-0069
复制
发表时间：
2019-12-01
期刊：
影响因子：
16.2
通讯作者：
Franklin, Jessica M.
中科院分区：
文献类型：
--
作者：
Patorno, Elisabetta;Schneeweiss, Sebastian;Franklin, Jessica M.
目的利用来自三个美国索赔数据集的真实世界数据(RWD)，我们旨在预测利格列汀和格列美脲治疗2型糖尿病(卡罗莱纳州)心血管结果试验的结果，通过一个新的框架，比较利格列汀和格列美脲在心血管风险增加的2型糖尿病患者(T2D)中的作用，该框架要求在分析主要结果之前通过预先指定的有效性检查。研究设计与方法在Medicare和两个商业索赔数据集(2011年5月至2015年9月)中，我们确定了1：1倾向得分匹配(PSM)队列，年龄40-85岁，心血管风险增加，通过采用卡罗莱纳州的资格标准服用利格列汀或格列美脲。PSM用于平衡>；120个混杂因素。有效性检查包括对预期功率、协变量平衡的评估，以及两个控制结果的评估，我们预期其相关性为正，结果为零。我们在根据卡罗莱纳州的主要终点评估综合心血管结果之前注册了该方案(ClinicalTrials.gov)。在每个数据源中估计风险比(HR)和95%的CI，并用固定效应荟萃分析合并。结果我们鉴定了24,131对利格列汀和格列美脲的PSM引发剂，它们具有足够的非劣效性(>；98%)。暴露组达到了良好的协变量平衡，包括关键的实验室结果，并复制了格列美脲和低血糖(HR 2.38[95%CI 1.79-3.13])和利格列汀与终末期肾脏疾病(HR 1.08[0.66-1.79])之间的预期关联。在CI包括零值(HR 0.91[0.79-1.05])的综合心血管结局中，利那格平与9%的风险降低相关，与非劣势一致。结论在一项非随机化的RWD研究中，我们发现与格列美脲相比，利格列汀具有复合心血管结局的非劣势风险。
OBJECTIVE Using real-world data (RWD) from three U.S. claims data sets, we aim to predict the findings of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA) comparing linagliptin versus glimepiride in patients with type 2 diabetes (T2D) at increased cardiovascular risk by using a novel framework that requires passing prespecified validity checks before analyzing the primary outcome. RESEARCH DESIGN AND METHODS Within Medicare and two commercial claims data sets (May 2011-September 2015), we identified a 1:1 propensity score-matched (PSM) cohort of T2D patients 40-85 years old at increased cardiovascular risk who initiated linagliptin or glimepiride by adapting eligibility criteria from CAROLINA. PSM was used to balance >120 confounders. Validity checks included the evaluation of expected power, covariate balance, and two control outcomes for which we expected a positive association and a null finding. We registered the protocol (, ClinicalTrials.gov) before evaluating the composite cardiovascular outcome based on CAROLINA's primary end point. Hazard ratios (HR) and 95% CIs were estimated in each data source and pooled with a fixed-effects meta-analysis. RESULTS We identified 24,131 PSM pairs of linagliptin and glimepiride initiators with sufficient power for noninferiority (>98%). Exposure groups achieved excellent covariate balance, including key laboratory results, and expected associations between glimepiride and hypoglycemia (HR 2.38 [95% CI 1.79-3.13]) and between linagliptin and end-stage renal disease (HR 1.08 [0.66-1.79]) were replicated. Linagliptin was associated with a 9% decreased risk in the composite cardiovascular outcome with a CI including the null (HR 0.91 [0.79-1.05]), in line with noninferiority. CONCLUSIONS In a nonrandomized RWD study, we found that linagliptin has noninferior risk of a composite cardiovascular outcome compared with glimepiride.