SGLT2 inhibitors for the prevention and treatment of heart failure: A scientific statement of the HFA and the HFAI

In the 2021 European Society of Cardiology (ESC) heart failure (HF) guidelines, sodium–glucose cotransporter 2 (SGLT2) inhibitors were recommended for the prevention of HF in patients with type 2 diabetes mellitus (T2DM) and for the treatment of HF with reduced ejection fraction (HFrEF). Further trials showed efficacy of empagliflozin and dapagliflozin in patients with HF with preserved ejection fraction (HFpEF). These results prompted a broadened recommendation for the SGLT2 inhibitors dapagliflozin or empagliflozin across the whole left ventricular ejection fraction (LVEF) spectrum in the 2023 Focused Update of the ESC HF guidelines and in other international guidelines. In SOLOIST-WHF and EMPULSE, sotagliflozin (enrolling only patients with T2DM) and empagliflozin, respectively, were beneficial when initiated at the end or soon after an episode of decompensated HF. Based on these results and on the early appearance of their beneficial effects, the administration of SGLT2 inhibitors should start early in patients hospitalized for acute HF. Analyses after study drug withdrawal in randomized clinical trials have shown that their benefits may decline rapidly after discontinuation, and thus, persistence of treatment is advised. In EMPACT-MI, empagliflozin did not reduce the primary outcome of cardiovascular (CV) death/HF hospitalization but reduced first/recurrent HF hospitalizations. Potential benefits of SGLT2 inhibitors in further specific conditions (i.e., cardiac amyloidosis, grown-up congenital heart disease and paediatric patients with HF) have been reported in observational studies but need confirmation from prospective trials. This scientific statement summarizes current evidence regarding the effects of SGLT2 inhibitors for the prevention and treatment of HF.