Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy.
Humanitas Clinical and Research Hospital IRCCS, Rozzano-Milan, Italy.
Cardiovasc Hematol Agents Med Chem. 2022;20(2):90-102. doi: 10.2174/1871525719666210809121016.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-diabetic agents that block the reabsorption of glucose in the proximal convoluted tubule of the nephron, thereby contributing to glycosuria and lowering blood glucose levels. SGLT2 inhibitors have been associated with improved cardiovascular outcomes in patients with diabetes, including a reduced risk of cardiovascular death and hospitalizations for heart failure. Recently, DAPA-HF and EMPEROR REDUCED trials showed the beneficial cardiovascular effect of SGLT2 inhibitors in patients with heart failure with consistently reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Moreover, some exploratory studies suggested that these drugs improve Left Ventricular (LV) systolic function and oppose LV adverse remodeling in patients with HFrEF. However, the exact mechanisms that mediated for this benefit are not fully understood. Beyond glycemic control, enhanced natriuresis, increased erythropoiesis, improved endothelial function and changes in myocardial metabolism may all play an active role in SGLT2 inhibitors' cardiovascular benefits. A deep understanding of the pathophysiological interplay is key to define which HF phenotype could benefit more from SGLT2 inhibitors. Current evidence on the comparison of different HF etiologies is limited to posthoc subgroup analysis of DAPA-HF and EMPEROR-REDUCED, which showed similar outcomes in patients with or without ischemic HF. On the other hand, in earlier studies of patients suffering from diabetes, rates of classic ischemic endpoints, such as myocardial infarction, stroke or coronary revascularization, did not differ between patients treated with SGLT2 inhibitors or placebo. The aim of this review is to discuss whether SGLT2 inhibitors may improve prognosis in patients with ischemic HF, not only in terms of reducing re-hospitalizations and improving LV function but also by limiting coronary artery disease progression and ischemic burden.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是一类抗糖尿病药物，可阻止近曲小管对葡萄糖的重吸收，从而导致糖尿和降低血糖水平。SGLT2 抑制剂与糖尿病患者心血管结局的改善相关，包括降低心血管死亡和心力衰竭住院的风险。最近，DAPA-HF 和 EMPEROR-REDUCED 试验表明，SGLT2 抑制剂可改善射血分数降低的心力衰竭（HFrEF）患者的心血管获益，无论是否存在糖尿病。此外，一些探索性研究表明，这些药物可改善 HFrEF 患者的左心室（LV）收缩功能并对抗 LV 不良重构。然而，介导这种获益的确切机制尚不完全清楚。除了血糖控制外，增强的利钠作用、增加的红细胞生成、改善的内皮功能和心肌代谢的变化都可能在 SGLT2 抑制剂的心血管获益中发挥积极作用。深入了解病理生理学的相互作用是确定哪种 HF 表型可能从 SGLT2 抑制剂中获益更多的关键。目前关于不同 HF 病因学比较的证据仅限于 DAPA-HF 和 EMPEROR-REDUCED 的事后亚组分析，这些研究表明在有或没有缺血性 HF 的患者中，结果相似。另一方面，在糖尿病患者的早期研究中，SGLT2 抑制剂治疗与安慰剂治疗的患者之间，经典的缺血性终点（如心肌梗死、中风或冠状动脉血运重建）的发生率没有差异。本综述的目的是讨论 SGLT2 抑制剂是否可以改善缺血性 HF 患者的预后，不仅可以减少再住院和改善 LV 功能，还可以限制冠状动脉疾病的进展和缺血性负担。
