Krämer Bernhard K, Hauske Sibylle J, Chilton Robert, Mann Johannes F E, Gullestad Lars, Fitchett David, Mattheus Michaela, Steubl Dominik, Wanner Christoph
Vth Department of Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany; European Center for Angioscience ECAS, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Vth Department of Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany; Boehringer Ingelheim International GmbH, Ingelheim, Germany.
J Diabetes Complications. 2023 Sep;37(9):108588. doi: 10.1016/j.jdiacomp.2023.108588. Epub 2023 Aug 17.
Evaluate changes in haemodynamic markers as mediators of cardiovascular (CV) and kidney benefits with empagliflozin.
Post-hoc analysis of EMPA-REG OUTCOME in patients with type 2 diabetes (T2D) and established CV disease receiving empagliflozin (10 and 25 mg) or placebo. Outcomes were CV death, hospitalisation for heart failure [HF], HF death, incident/worsening nephropathy, new onset macroalbuminuria, and the composite of sustained estimated glomerular filtration rate decline ≥40 % from baseline, renal replacement therapy or renal death. To be considered a mediator, changes in variable (pulse pressure, mean arterial pressure and cardiac workload) over time had to be (1) affected by active treatment, (2) associated with the outcome, and (3) adjustment for changes over time must reduce treatment effect versus an unadjusted analysis. Variables were evaluated in Cox regression analyses.
Pulse pressure, mean arterial pressure and cardiac workload were significantly reduced by empagliflozin vs placebo. Using change from baseline to Week 12 or sensitivity analyses (time-dependent updated mean and current change from baseline) of these CV parameters, only small impacts on empagliflozin effect on CV and kidney outcomes were shown.
Improvements in haemodynamic parameters did not substantially mediate empagliflozin benefits on CV and kidney outcomes in patients with T2DM and established CV disease.
评估血流动力学标志物的变化，作为恩格列净对心血管（CV）和肾脏有益作用的介导因素。
对2型糖尿病（T2D）且患有已确诊CV疾病、接受恩格列净（10毫克和25毫克）或安慰剂治疗的患者进行EMPA-REG OUTCOME事后分析。结局指标包括CV死亡、因心力衰竭（HF）住院、HF死亡、新发/恶化的肾病、新发大量白蛋白尿，以及持续估计肾小球滤过率自基线下降≥40%、肾脏替代治疗或肾脏死亡的复合结局。要被视为介导因素，变量（脉压、平均动脉压和心脏负荷）随时间的变化必须满足以下条件：（1）受活性治疗影响；（2）与结局相关；（3）对随时间变化进行调整后，与未调整分析相比，必须降低治疗效果。在Cox回归分析中评估变量。
与安慰剂相比，恩格列净显著降低了脉压、平均动脉压和心脏负荷。使用从基线到第12周的变化或对这些CV参数的敏感性分析（时间依赖性更新均值和自基线的当前变化），结果显示对恩格列净在CV和肾脏结局方面的效果仅有微小影响。
血流动力学参数的改善并未实质性介导恩格列净对T2DM且患有已确诊CV疾病患者的CV和肾脏结局的有益作用。
