Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Department of Endocrinology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
ESC Heart Fail. 2022 Aug;9(4):2239-2248. doi: 10.1002/ehf2.14005. Epub 2022 Jun 1.
Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with comparable poor outcomes as other subtypes of heart failure and remains a medical unmet need due to the paucity of effective therapies. According to large cardiovascular (CV) outcome trials in patients with heart failure, sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce CV mortality and hospitalizations for heart failure in patients with heart failure across the spectrum of left ventricular ejection fraction (LVEF). There has been a lack of dedicated trials in HFmrEF. However, several large outcome trials in heart failure that enrolled patients with HFmrEF could provide a hint on the role of SGLT2is in this subgroup. This review focuses on CV effects of three major SGLT2is-dapagliflozin, empagliflozin, and sotagliflozin-in patients with HFmrEF. A narrative review of trials investigating the efficacy of each medication in treating heart failure with LVEF > 40% is provided with a focus on their LVEF subgroup analyses. The purpose of this review is to discuss the current state of evidence regarding the potential of SGLT2is in HFmrEF management. Current limited evidence suggests that SGLT2is might be a favourable treatment modality for patients with HFmrEF to reduce hospitalization for heart failure and CV mortality. This conclusion needs to be further supported by clear HFmrEF subgroup analysis of the existing trials. Further outcome trials involving sufficient patients with different subtypes of HFmrEF are needed to confirm and assess CV benefits of SGLT2is in HFmrEF. Possible mechanisms by which SGLT2is exert their cardioprotective effect are also described briefly.
射血分数轻度降低的心力衰竭（HFmrEF）与其他类型心力衰竭的预后相当差，由于缺乏有效的治疗方法，仍然是医学上未满足的需求。根据心力衰竭患者的大型心血管（CV）结局试验，钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）可降低心力衰竭患者全射血分数（LVEF）范围内的 CV 死亡率和心力衰竭住院率。HFmrEF 缺乏专门的试验。然而，几项纳入 HFmrEF 患者的心力衰竭大型结局试验可能为 SGLT2i 在该亚组中的作用提供线索。这篇综述重点介绍了三种主要 SGLT2i-达格列净、恩格列净和索格列净在 HFmrEF 患者中的 CV 效应。对研究每种药物治疗 LVEF>40%心力衰竭疗效的试验进行了叙述性综述，重点介绍了它们的 LVEF 亚组分析。本综述的目的是讨论关于 SGLT2i 在 HFmrEF 管理中应用的现有证据状况。目前有限的证据表明，SGLT2i 可能是 HFmrEF 患者降低心力衰竭住院率和 CV 死亡率的有利治疗方法。这一结论需要现有试验的 HFmrEF 亚组分析进一步证实和评估。需要进一步的结局试验，纳入不同类型 HFmrEF 的足够患者，以确认和评估 SGLT2i 在 HFmrEF 中的 CV 获益。SGLT2i 发挥其心脏保护作用的可能机制也简要描述。
