In heart failure patients, cardiovascular death and heart failure hospitalization are reduced by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors. This is true irrespective of left ventricular ejection fraction (LVEF) status in these patients.

• In this meta-analysis of large (≥1,000 patients) randomized controlled trials from MEDLINE and EMBASE, the included studies assessed the impacts of SGLT2 inhibitors vs placebo in the setting of heart failure until September 2021.

• Four randomized controlled trials (DAPA HF, EMPEROR-Preserved, EMPEROR-Reduced, and SOLOIST-WHF) were analyzed (n = 15,684).

• A significant decrease in the composite of cardiovascular death and heart failure hospitalization (hazard ratio HR: 0.76) was achieved with SGLT2 inhibitors.

• This was found to be consistent in sub-groups of cases with LVEF ≤40% (n = 9,199, HR: 0.74) and LVEF >40% (n = 6,482, HR: 0.78), as well as in sub-groups of patients with and without diabetes mellitus at baseline.

• A significant decrease in cardiovascular death (HR: 0.87) and total heart failure hospitalization (risk ratio: 0.71) was observed in relation to treatment with SGLT2 inhibitors; although a potential trend towards decreased all-cause death was observed with SGLT2 inhibitors, there was no statistically significant difference (HR: 0.91).