Department of Cardiology (CVK) and Berlin Institute of Health Centre for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site, Berlin, Germany.
University of Mississippi School of Medicine, Jackson, MI, USA.
Eur J Heart Fail. 2019 Oct;21(10):1279-1287. doi: 10.1002/ejhf.1596. Epub 2019 Sep 16.
The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium-glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF.
The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities.
The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.
射血分数保留的心力衰竭（HFpEF）的主要生物学过程包括全身炎症、心外膜脂肪组织积聚、冠状动脉微循环稀疏、心肌纤维化和血管僵硬；由此导致的左心室和主动脉顺应性受损（尤其是伴有肾小球功能受损和钠潴留时）会导致心脏充盈压升高和运动性呼吸困难，尽管左心室射血分数相对保留。钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂除了对血糖的作用外，还具有广泛的生物学作用（包括抑制心脏炎症和纤维化、拮抗钠潴留和改善肾小球功能），可改善 HFpEF 的病理生理紊乱。这些 SGLT2 抑制剂在 HFpEF 的实验模型中表现出有利的效果，并在大型试验中发现可降低 2 型糖尿病患者发生严重心力衰竭事件的风险，其中许多患者被回顾性地确定为患有 HFpEF。
EMPEROR-Preserved 试验正在招募约 5750 名 HFpEF（射血分数>40%）患者，无论是否患有 2 型糖尿病，他们被随机分为安慰剂组或恩格列净 10mg/天组，恩格列净在此基础上添加了所有适合 HFpEF 和合并症的治疗。
主要终点是心血管死亡或心力衰竭住院的复合风险的首次事件时间分析。该试验还将评估恩格列净对肾功能、心血管死亡、全因死亡率和再住院事件的影响，并评估广泛的生物标志物，这些标志物反映了可能推动 HFpEF 发展的重要病理生理机制。EMPEROR-Preserved 试验很有希望确定恩格列净是否能对 HFpEF 的病程产生有意义的影响，而目前 HFpEF 的治疗选择很少。
