Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus.
Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus.
复制标题
DOI：
10.1111/dom.14769
复制
发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂已被证明可以降低因心力衰竭 (HHF) 和复合肾脏结局住院的风险，但这些益处背后的调节因素尚不清楚。 VERTIS CV 是一项将 2 型糖尿病和动脉粥样硬化性心血管疾病患者随机分配到艾格列净与安慰剂组的试验，在参与者中，使用 Cox 比例风险回归模型评估了艾格列净功效对 26 个潜在介质中第一个 HHF 和肾脏复合结果的调节百分比。使用时间依赖性方法来评估协变量的早期（从基线到第一次基线后测量的变化）和平均（使用所有基线后测量的从基线变化的加权平均值）变化与临床结果之间的关联。对于 HHF 分析，四种生物标志物（血红蛋白、红细胞比容、血清白蛋白和尿酸盐）的早期变化和七种生物标志物（早期生物标志物 + 体重、氯化物和血清蛋白）的平均变化被确定为满足作为艾格列净对 HHF 风险影响的介质的标准。复合肾脏结局也观察到类似的结果，四种生物标志物（糖化血红蛋白、血红蛋白、血细胞比容和尿酸盐）的早期变化以及五种生物标志物的平均变化（早期生物标志物（非糖化血红蛋白） + 体重、血清白蛋白）介导了艾格列净对肾脏结局的影响。在 VERTIS CV 试验的这些分析中，容量状态和血液浓缩和/或造血功能的标志物是艾格列净降低早期和平均变化期 HHF 风险和复合肾脏结局的最强调节因素。 NCT01986881
Sodium‐glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalization for heart failure (HHF) and composite kidney outcomes, but the mediators underlying these benefits are unknown. Among participants from VERTIS CV, a trial of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease randomized to ertugliflozin versus placebo, Cox proportional hazards regression models were used to evaluate the percentage mediation of ertugliflozin efficacy on the first HHF and kidney composite outcome in 26 potential mediators. Time‐dependent approaches were used to evaluate associations between early (change from baseline to the first post‐baseline measurement) and average (weighted average of change from baseline using all post‐baseline measurements) changes in covariates with clinical outcomes. For the HHF analyses, early changes in four biomarkers (haemoglobin, haematocrit, serum albumin and urate) and average changes in seven biomarkers (early biomarkers + weight, chloride and serum protein) were identified as fulfilling the criteria as mediators of ertugliflozin effects on the risk of HHF. Similar results were observed for the composite kidney outcome, with early changes in four biomarkers (glycated haemoglobin, haemoglobin, haematocrit and urate), and average changes in five biomarkers [early biomarkers (not glycated haemoglobin) + weight, serum albumin] mediating the effects of ertugliflozin on the kidney outcome. In these analyses from the VERTIS CV trial, markers of volume status and haemoconcentration and/or haematopoiesis were the strongest mediators of the effect of ertugliflozin on reducing risk of HHF and composite kidney outcomes in the early and average change periods. NCT01986881
登录
查看更多内容
影响因子：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
影响因子：
37.8
作者：
Givertz MM;Anstrom KJ;Redfield MM;Deswal A;Haddad H;Butler J;Tang WH;Dunlap ME;LeWinter MM;Mann DL;Felker GM;O'Connor CM;Goldsmith SR;Ofili EO;Saltzberg MT;Margulies KB;Cappola TP;Konstam MA;Semigran MJ;McNulty SE;Lee KL;Shah MR;Hernandez AF;NHLBI Heart Failure Clinical Research Network
通讯作者：
NHLBI Heart Failure Clinical Research Network
影响因子：
5.5
作者：
Borghi, Claudio;Cosentino, Eugenio R.;Cicero, Arrigo F. G.
通讯作者：
Cicero, Arrigo F. G.
影响因子：
5.4
作者：
Croteau D;Luptak I;Chambers JM;Hobai I;Panagia M;Pimentel DR;Siwik DA;Qin F;Colucci WS
通讯作者：
Colucci WS
影响因子：
1.6
作者：
El Iskandarani M;El Kurdi B;Murtaza G;Paul TK;Refaat MM
通讯作者：
Refaat MM