Sodium-glucose cotransporter 2 inhibitors as a treatment for heart failure

Abstract

© Author(s) (or their employer(s)) 2021. No commercial reuse. See rights and permissions. Published by BMJ. INTRODUCTION Despite advances in both the pharmacological and the devicebased management of heart failure with reduced ejection fraction (HFrEF), patients remain at a high risk of morbidity and mortality. The last decade has seen a new era in the pharmacological management of HFrEF with four drug classes affecting five distinct physiological pathways now established as cornerstones of HFrEF pharmacotherapy: an angiotensin receptorneprilysin inhibitor (ARNI) in the form of sacubitril/valsartan, betablockers, mineralocorticoid receptor antagonists (MRA) and, most recently, sodiumglucose cotransporter 2 inhibitors (SGLT2i). Originally investigated as glucoselowering agents, SGLT2i in randomised, placebocontrolled trials prevented the development of heart failure (HF) in patients with type 2 diabetes with established or at high risk of cardiovascular disease. The clinical benefits of SGLT2i were independent of their glucoselowering effect. Subsequently, two large, randomised, placebocontrolled trials have reported that SGLT2i (dapagliflozin and empagliflozin) improved morbidity and mortality in patients with HFrEF, irrespective of diabetes status. 7 A further trial has reported on the benefits of sotagliflozin, a combined SGLT1 and SGLT2 inhibitor, in patients with diabetes and hospitalised HF. The purpose of this article is to provide background on the use of SGLT2i in patients with HF, review the evidence for their use, suggest how they may be implemented in clinical practice as a new cornerstone in the management of patients with HFrEF and discuss ongoing trials of SGLT2i across the HF landscape.