Department of Therapeutics, Marseille, France,
Department of Cardiology, Hôpital de la Timone, Marseille, France,
Cardiology. 2020;145(6):370-374. doi: 10.1159/000506004. Epub 2020 Feb 21.
The value of glycosylated hemoglobin (HbA1c) as a surrogate marker for the prevention of cardiovascular outcomes on antidiabetic drugs is debated. The 2008 FDA guidance led to multiple large clinical trials to evaluate the effect of new antidiabetic drugs versus placebo on major adverse cardiac events (MACE). The aim of this study was to evaluate the relation between MACE and HbA1c decrease between antidiabetic drug and placebo across the spectrum of cardiovascular outcome trials (CVOT).
In this systematic review, we included randomized controlled trials that compared an antidiabetic drug to placebo in addition to current standard of care with the primary intention of demonstrating cardiovascular safety. We investigated the relationship between MACE decrease on antidiabetic drug and HbA1c reduction on antidiabetic drug using the coefficient correlation. We also studied the effects of potential confounders on MACE decrease.
Fourteen eligible trials including 128,149 patients were included, 12,114 of whom experienced MACE. Mean achieved HbA1c absolute reductions on antidiabetic treatment versus placebo varied from 0.29 to 1%. The decrease of MACE on antidiabetic drug was significantly correlated with mean HbA1c reduction (r = 0.88, 95% CI: 0.67-0.96, p < 0.001) and weight loss (r = 0.81, 95% CI: 0.46-0.94, p < 0.001). In a bivariate model including weight loss, only HbA1c reduction remained significantly correlated with the decrease of MACE on antidiabetic drug (p = 0.019).
Across CVOT, the decrease in MACE incidence on various antidiabetic drugs is significantly correlated with HbA1c reduction. This meta-analysis supports HbA1c as an appropriate surrogate endpoint for cardiovascular events. Our analysis supports that changes in HbA1c should be taken into account while interpreting effects of new antidiabetic drugs on cardiovascular outcomes.
糖化血红蛋白（HbA1c）作为抗糖尿病药物预防心血管结局的替代标志物的价值存在争议。2008 年 FDA 的指导意见导致了多项大型临床试验，以评估新型抗糖尿病药物与安慰剂相比在主要不良心脏事件（MACE）上的疗效。本研究的目的是评估在心血管结局试验（CVOT）的范围内，各种抗糖尿病药物与安慰剂相比的 MACE 减少与 HbA1c 降低之间的关系。
在这项系统评价中，我们纳入了比较抗糖尿病药物与安慰剂加当前标准治疗的随机对照试验，主要目的是证明心血管安全性。我们使用相关系数评估了抗糖尿病药物的 MACE 减少与 HbA1c 降低之间的关系。我们还研究了潜在混杂因素对 MACE 减少的影响。
纳入了 14 项合格的试验，共纳入 128149 例患者，其中 12114 例发生了 MACE。抗糖尿病治疗与安慰剂相比，HbA1c 的平均绝对降低幅度从 0.29%到 1%不等。抗糖尿病药物的 MACE 减少与平均 HbA1c 降低显著相关（r=0.88，95%CI：0.67-0.96，p<0.001）和体重减轻（r=0.81，95%CI：0.46-0.94，p<0.001）。在包括体重减轻的双变量模型中，只有 HbA1c 降低与抗糖尿病药物的 MACE 减少显著相关（p=0.019）。
在 CVOT 中，各种抗糖尿病药物的 MACE 发生率降低与 HbA1c 降低显著相关。这项荟萃分析支持 HbA1c 作为心血管事件的合适替代终点。我们的分析支持在解释新型抗糖尿病药物对心血管结局的影响时，应考虑 HbA1c 的变化。
