Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy.
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Cardiovasc Diabetol. 2021 May 10;20(1):103. doi: 10.1186/s12933-021-01300-y.
Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs.
We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals.
Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74-1.03) in the target population, compared to 0.86 (0.74-0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77-0.99) in the target population compared to 0.87 (0.78-0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population.
Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.
将心血管结局试验（CVOT）的结果转化到真实世界环境中具有挑战性。本研究将 CVOT 结果转化为常规临床实践中观察到的 2 型糖尿病（T2D）患者人群，并可能接受 CVOT 中测试的药物。
我们实施了基于 CVOT 汇总数据和目标人群糖尿病门诊患者个体数据的后分层方法。我们使用 CVOT 中提供的分层特定估计值，通过根据目标人群中给定特征的比例对分层特定治疗效果的平均值进行加权，来计算目标人群的预期效果大小。数据以危险比（HR）和 95%置信区间表示。
与目标人群（n=139708）相比，CVOT 人群（n=95816）更年轻，且心血管疾病的患病率高 2 至 3 倍。在具有各种关于分层特定效果细节的 CVOT 中，EMPA-REG 排名第一，其次是 TECOS，而 DECLARE 和 PIONEER-6 的分层特定信息较为有限。基于 EMPA-REG 的 3 点主要不良心血管事件（MACE）的后分层 HR 估计值在目标人群中为 0.88（0.74-1.03），而在试验中为 0.86（0.74-0.99）。在目标人群中，基于 LEADER 的 HR 估计值为 0.88（0.77-0.99），而在试验中为 0.87（0.78-0.97）。在 SUSTAIN-6、EXSCEL、PIONEER-6 和 DECLARE 中也得到了一致的结果。CVOT 中观察到的 DPP-4 抑制剂的作用在目标人群中保持中性。
基于 CVOT 分层特定效果，在 CVOT 中测试的降低血糖药物的心血管保护作用可转移到 T2D 患者的真实世界人群中。
