Aguilar-Gallardo Jose S, Correa Ashish, Contreras Johanna P
Department of Medicine, Mount Sinai Morningside, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eur Heart J Cardiovasc Pharmacother. 2022 May 5;8(3):311-321. doi: 10.1093/ehjcvp/pvab056.
The heart and the kidneys are closely interconnected, and disease in one organ system can lead to disease in the other. This interdependence is illustrated in heart failure with reduced ejection fraction (HFrEF), where worsening heart failure (HF) can lead to renal dysfunction and vice versa. Further complicating this situation is the fact that drugs that serve as guideline-directed medical therapy for HFrEF can affect renal function. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of medication with an evolving role in HF and chronic kidney disease (CKD). Initially found to have benefits in diabetic patients, new research established potential cardiovascular and renal benefits in patients with HF independent of their diabetic status and in populations with CKD. This has been established by landmark trials such as EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), EMPA-TROPISM (Are the 'Cardiac Benefits' of Empagliflozin Independent of Its Hypoglycemic Activity), CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction). Multiple mechanisms responsible for these benefits have been suggested by clinical and non-clinical studies, and involve cardiac and renal energetic efficiency, cardiac remodelling, preservation of renal function, immunomodulation, changes in haematocrit, and control of risk factors. As such, SGLT2 inhibitors have tremendous potential to improve outcomes in populations with HF and CKD. The purpose of this review is to discuss the current evidence and underlying mechanisms for the cardio-renal benefits of SGLT2 inhibitors in patients with HFrEF.
心脏和肾脏紧密相连，一个器官系统的疾病会导致另一个器官系统发病。这种相互依存关系在射血分数降低的心力衰竭（HFrEF）中得到体现，即心力衰竭（HF）病情恶化会导致肾功能障碍，反之亦然。使这种情况更加复杂的是，作为HFrEF指南指导药物治疗的药物会影响肾功能。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是一类新型药物，在HF和慢性肾脏病（CKD）中的作用不断演变。最初发现其对糖尿病患者有益，新的研究证实，无论糖尿病状态如何，HF患者以及CKD人群均可从SGLT2抑制剂中获得潜在的心血管和肾脏益处。这已通过多项具有里程碑意义的试验得到证实，如EMPEROR-Reduced（恩格列净治疗慢性心力衰竭和射血分数降低患者的结局试验）、EMPA-TROPISM（恩格列净的“心脏益处”是否独立于其降糖活性）、CREDENCE（卡格列净与糖尿病肾病临床评估中的肾脏事件）、DAPA-CKD（达格列净与慢性肾脏病不良结局的预防）、DAPA-HF（达格列净与心力衰竭不良结局的预防）以及DEFINE-HF（达格列净对射血分数降低的HF患者生物标志物、症状和功能状态的影响）。临床和非临床研究提出了多种促成这些益处的机制，包括心脏和肾脏的能量效率、心脏重塑、肾功能的维持、免疫调节、血细胞比容变化以及危险因素的控制。因此，SGLT2抑制剂在改善HF和CKD人群结局方面具有巨大潜力。本综述的目的是讨论SGLT2抑制剂对HFrEF患者心肾益处的现有证据及潜在机制。
