Evaluation of cardiovascular and renal outcomes with ertugliflozin: what is the VERdict from the VERTIS-CV trial?

A growing number of antidiabetic agents have demonstrated cardiovascular and renal benefits in cardiovascular outcome trials (CVOTs), despite such trials being principally required to rule out excess cardiovascular risk. This article addresses the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS-CV) trial, its background, design, results, and implications. In patients at least 40 years of age with atherosclerotic cardiovascular disease (ASCVD), the VERTIS-CV trial demonstrated ertugliflozin was non-inferior to placebo for major adverse cardiovascular events, though not superior. Ertugliflozin significantly reduced hospitalization for heart failure compared to placebo. The composite renal outcome was not significantly different between groups. Ertugliflozin was generally well tolerated with a safety profile commensurate with other sodium-glucose co-transporter-2 inhibitors (SGLT-2) inhibitors. In patients with type 2 diabetes and ASCVD, ertugliflozin appears safe with a noted non-significant trend toward improved renal outcomes. Approximately 23.7% of patients in the VERTIS-CV trial had heart failure, the highest among SGLT-2 inhibitor CVOTs. The VERTIS-CV trial reaffirms the reduction in heart failure hospitalizations as a likely class effect of SGLT-2 inhibitors. While the trial supports the use of ertugliflozin beyond glycemic control, agents with confirmed superiority for improved cardiovascular outcomes and mortality may be preferred.

越来越多的降糖药物（antidiabetic agents）在心血管结局试验（cardiovascular outcome trials, CVOTs）中被证实具有心血管与肾脏获益，尽管此类试验的核心设立目的是排除过度的心血管风险。本文系统阐述了艾托格列净疗效与安全性心血管结局试验（Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes, VERTIS-CV）的背景、试验设计、研究结果及其临床意义。针对合并动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease, ASCVD）且年龄≥40岁的患者，VERTIS-CV试验结果显示，艾托格列净对比安慰剂在主要不良心血管事件（major adverse cardiovascular events）方面非劣效，但未体现出优效性。相较于安慰剂，艾托格列净可显著降低心力衰竭（heart failure）住院风险。两组的复合肾脏结局无显著统计学差异。艾托格列净整体耐受性良好，安全性特征与其他钠-葡萄糖协同转运蛋白2抑制剂（sodium-glucose co-transporter-2 inhibitors, SGLT-2抑制剂）一致。针对合并2型糖尿病（type 2 diabetes）与ASCVD的患者，艾托格列净安全性良好，其肾脏结局呈现改善趋势，但该趋势未达到统计学显著性。VERTIS-CV试验中约23.7%的受试者合并心力衰竭，这一比例在SGLT-2抑制剂相关CVOTs中位居最高。该试验进一步证实，降低心力衰竭住院风险是SGLT-2抑制剂的潜在类效应。尽管本试验支持艾托格列净可超越血糖控制的适用范围，但对于已被证实可改善心血管结局与降低死亡率的降糖药物，临床实践中或优先选用此类药物。