Cherney David Z I, Frederich Robert, Pratley Richard E, Cosentino Francesco, Dagogo-Jack Samuel, Pong Annpey, Gantz Ira, Cater Nilo B, Mancuso James P, Masiukiewicz Urszula, Cannon Christopher P
University of Toronto, Toronto, ON, Canada.
Pfizer Inc., Groton, CT, USA.
Kidney Dis (Basel). 2025 Feb 4;11(1):63-74. doi: 10.1159/000543162. eCollection 2025 Jan-Dec.
VERTIS CV was a placebo-controlled cardiovascular (CV) outcome trial evaluating the sodium-glucose cotransporter 2 inhibitor ertugliflozin in patients with type 2 diabetes and established atherosclerotic CV disease. The aim of the current analyses was to evaluate VERTIS CV cardiorenal outcomes according to baseline use of renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics, including mineralocorticoid receptor antagonists (MRAs).
Participants received ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo once daily and were followed for a mean of 3.5 years. Prespecified CV and kidney outcomes were analyzed by Cox proportional hazard modeling in participant subgroups defined by baseline use of RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) or diuretics (loop diuretics, non-loop diuretics, MRAs), with interaction testing to assess for treatment effect modification.
A total of 8,246 patients were randomized in VERTIS CV. At baseline, 6,686 (81%) participants were being treated with RAAS inhibitors, 3,542 (43%) with diuretics, 1,252 (15%) with loop diuretics, and 674 (8%) with MRAs. No significant interactions were observed for cardiorenal outcomes by baseline use of RAAS inhibitors or MRAs ( > 0.05 for all). Statistically significant interactions for a first event of hospitalization for heart failure (HHF) or CV death, and of HHF (alone), were observed with baseline use of diuretics, including loop diuretics, with an increased benefit of ertugliflozin treatment versus placebo.
In VERTIS CV, baseline use of diuretics, particularly loop diuretics, identified a subgroup that demonstrated greater benefit with ertugliflozin on first HHF/CV death and HHF outcomes, with no modification of treatment effect observed with baseline use of RAAS inhibitors or MRAs. There was no evidence of treatment effect on the kidney composite outcomes by baseline use of RAAS inhibitors, diuretics, loop diuretics, or MRAs.
VERTIS CV是一项安慰剂对照的心血管（CV）结局试验，旨在评估钠-葡萄糖协同转运蛋白2抑制剂依帕列净在2型糖尿病合并已确诊动脉粥样硬化性CV疾病患者中的疗效。当前分析的目的是根据肾素-血管紧张素-醛固酮系统（RAAS）抑制剂或利尿剂（包括盐皮质激素受体拮抗剂（MRA））的基线使用情况，评估VERTIS CV的心肾结局。
参与者每日一次接受5毫克依帕列净、15毫克依帕列净或安慰剂治疗，平均随访3.5年。通过Cox比例风险模型在由RAAS抑制剂（血管紧张素转换酶抑制剂、血管紧张素II受体阻滞剂）或利尿剂（袢利尿剂、非袢利尿剂、MRA）的基线使用情况定义的参与者亚组中分析预先指定的CV和肾脏结局，并进行交互作用检验以评估治疗效果的修饰作用。
VERTIS CV共随机纳入8246例患者。基线时，6686例（81%）参与者正在接受RAAS抑制剂治疗，3542例（43%）接受利尿剂治疗，1252例（15%）接受袢利尿剂治疗，674例（8%）接受MRA治疗。根据RAAS抑制剂或MRA的基线使用情况，在心肾结局方面未观察到显著的交互作用（所有P>0.05）。对于心力衰竭住院（HHF）或CV死亡的首次事件以及单独的HHF，观察到与袢利尿剂等利尿剂的基线使用存在统计学显著的交互作用，与安慰剂相比，依帕列净治疗的获益增加。
在VERTIS CV中，利尿剂尤其是袢利尿剂的基线使用确定了一个亚组，该亚组在首次HHF/CV死亡和HHF结局方面使用依帕列净显示出更大的获益，而根据RAAS抑制剂或MRA的基线使用情况未观察到治疗效果的修饰作用。没有证据表明RAAS抑制剂、利尿剂、袢利尿剂或MRA的基线使用对肾脏复合结局有治疗效果。
