Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.
Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.
复制标题
DOI：
10.1161/circulationaha.117.030012
复制
发表时间：
2017-10-24
期刊：
影响因子：
37.8
通讯作者：
Cherney DZI
中科院分区：
文献类型：
--
作者：
Lytvyn Y;Bjornstad P;Udell JA;Lovshin JA;Cherney DZI
尽管目前已建立治疗，但心力衰竭（HF）仍然是全球住院和死亡的主要原因。因此，需要新的治疗靶点来改善HF患者的预后。EMPA-REG OUTCOME试验证明，在2型糖尿病（T2 D）和心血管疾病患者中，使用降糖药恩格列净（一种钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂）可显著降低死亡率和HF住院风险。CANVAS试验随后报告了3点MACE（主要不良心血管事件）和HF住院风险的降低。虽然SGLT 2抑制可能具有超越T2 D（包括HF）的潜在应用，但SGLT 2抑制剂的心脏保护作用机制仍不完全清楚。SGLT 2抑制促进钠尿和渗透性利尿，导致血浆容量收缩和前负荷降低，以及血压、动脉僵硬度和后负荷降低，从而改善HF患者的内分泌下血流。SGLT 2抑制也与肾功能保护相关。基于机制研究和临床试验的数据，SGLT 2抑制剂的大型临床试验目前正在研究SGLT 2抑制剂在伴和不伴T2 D的HF患者中的潜在用途。因此，在本综述中，我们总结了SGLT 2抑制剂的关键药效学作用以及支持在T2 D HF患者中使用SGLT 2抑制剂的基本原理的临床证据。由于推测这些有利作用的发生与血糖降低无关，因此我们还探索了SGLT 2抑制在无T2 D伴HF或有HF风险的患者（如冠状动脉疾病或高血压患者）中的潜在用途。最后，我们提供了正在进行的SGLT 2抑制剂心血管结局试验的详细概述和总结。
Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin – a sodium glucose co-transporter 2 (SGLT2) inhibitor. The CANVAS trial subsequently reported a reduction in 3-point MACE (major adverse cardiovascular events) and HF hospitalization risk. While SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, as well as decreases in blood pressure, arterial stiffness and afterload, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients with HF with and without T2D. Accordingly, in this review, we summarize key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence which support the rationale for the use of SGLT2 inhibitors in HF patients with T2D. Since presumably these favorable effects occur independent of blood-glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.