Sodium-glucose cotransporter 2 (SGLT2) inhibitors have previously demonstrated cardioprotective properties in patients with type 2 diabetes, suggesting a preventive effect on heart failure (HF). The trial program investigates the therapeutic potential for HF prevention by evaluating the cardiac, metabolic, and renal effects of the SGLT2 inhibitor empagliflozin in patients with increased risk of developing HF, but without diabetes or established HF. The trial program is an investigator-initiated, double-blind, randomized clinical trial program including elderly and obese patients (60-84 years, body mass index >28 kg/m) with at least one manifestation of hypertension, cardiovascular or chronic kidney disease, but no history of diabetes or HF. The aims are to investigate the effects of empagliflozin on 1) physical capacity and left ventricular and atrial structural changes with peak oxygen consumption and left ventricular mass as primary endpoints (), and 2) cardiac-adipose tissue interaction and volume homeostasis with primary endpoints of changes in epicardial adipose tissue and estimated extracellular volume (). At present, 138 of 204 patients have been randomized in the trial program. Patients are randomized 1:1 to 180 days treatment with empagliflozin 10 mg daily or placebo, while undergoing a comprehensive examination program at baseline and follow-up. The trial program will mark the first step towards elucidating the potential of SGLT2 inhibition for HF prevention in an outpatient setting in elderly and obese patients with increased risk of developing HF, but with no history of diabetes or established HF. Furthermore, the trial program will supplement the larger event-driven trials by providing mechanistic insights to the beneficial effects of SGLT2 inhibition. Both parts of the trial program have been registered on September 13th 2021 (Clinical Trial Registration numbers: NCT05084235 and NCT05042973) before enrollment of the first patient. All patients will provide oral and written informed consent. The trial is approved by The Regional Committee on Health Research Ethics and the Danish Medicines Agency. Data will be disseminated through scientific meetings and peer-reviewed journals irrespective of outcome.

中文翻译：

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恩格列净用于心力衰竭风险增加的老年和肥胖患者：Empire Prevent 试验计划的研究方案

钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂此前已证明对 2 型糖尿病患者具有心脏保护作用，表明对心力衰竭 (HF) 具有预防作用。该试验计划通过评估 SGLT2 抑制剂恩格列净对心力衰竭风险增加但没有糖尿病或已确诊心力衰竭的患者的心脏、代谢和肾脏影响，研究预防心力衰竭的治疗潜力。该试验项目是一项由研究者发起的、双盲、随机临床试验项目，包括患有至少一种高血压、心血管或慢性肾脏疾病表现的老年和肥胖患者（60-84岁，体重指数>28 kg/m） ，但无糖尿病或心力衰竭病史。目的是研究恩格列净对 1) 身体能力以及左心室和心房结构变化的影响，以峰值耗氧量和左心室质量为主要终点 ()，以及 2) 心脏-脂肪组织相互作用和容量稳态，以主要终点为心外膜脂肪组织和估计细胞外体积的变化（）。目前，204 名患者中的 138 名已被随机分配到该试验项目中。患者按照 1:1 的比例随机接受每日 10 mg 恩格列净或安慰剂的 180 天治疗，同时在基线和随访时接受全面的检查计划。该试验计划将标志着阐明 SGLT2 抑制在门诊环境中预防心力衰竭的潜力的第一步，对象是老年和肥胖患者，这些患者发生心力衰竭的风险增加，但没有糖尿病史或已确诊的心力衰竭。此外，该试验计划将通过提供关于 SGLT2 抑制的有益效果的机制见解来补充更大规模的事件驱动试验。试验计划的两个部分均已于 2021 年 9 月 13 日在第一位患者入组之前完成注册（临床试验注册号：NCT05084235 和 NCT05042973）。所有患者都将提供口头和书面知情同意书。该试验得到了地区健康研究伦理委员会和丹麦药品管理局的批准。无论结果如何，数据都将通过科学会议和同行评审期刊传播。