SGLT-2 inhibitors: A step forward in the treatment of heart failure with reduced ejection fraction.

Heart failure (HF) is a major health problem with a significant impact on morbidity, mortality, quality of life and healthcare costs. Despite the positive impact of disease-modifying therapies developed over the last four decades, HF mortality and hospitalization remain high. We aim at reviewing the evidence supporting the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, as a novel strategy for HF with reduced ejection fraction (HFrEF) treatment. The consistent observation of a reduction in HF hospitalizations in type-2 diabetes cardiovascular safety trials EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS raised the hypothesis that SGLT-2 inhibitors could have an impact in HF treatment. This hypothesis was first confirmed in 2019 with the DAPA-HF publication showing that dapagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations and cardiovascular mortality. This was reinforced by the EMPEROR-Reduced publication in 2020 showing that empagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations. Both studies established SGLT-2 inhibitors as a fourth pillar of HFrEF prognosis-modifying therapy, in addition to the gold standard triple neurohormonal modulation/blockade.