Actualization of Positions of Gliflozins in Treatment Algorithms for Patients with Heart Failure: Chronology of Success

INTRODUCTION: Despite the efforts of the cardiologic communities to introduce approaches to treatment of heart failure (HF) based on the highest level of evidence, HF remains one of the “least satisfied demands in the therapy of cardiovascular diseases” due to high prevalence, poor prognosis and insufficient use of treatment methods with clinically proven effectiveness. The article considers chronology of study and introduction of sodium-glucose cotransporter 2 inhibitors (syn.: gliflozins; SGLT2is) in clinical practice from the moment of creation of the first drug of this group ― florizin ― and further, stepwise with the change of the therapeutic paradigm as the result of performed clinical trials. Thus, EMPAREG OUTCOME, CANVAS, DECLARE-TIMI 58 studies demonstrated that SGLT2is not only produce a glucosuric effect, but also reduce the development and progression of HF and increase the life expectancy of patients with type 2 diabetes mellitus (DM2) and with reduced left ventricular ejection fraction (LFEF). DAPA-HF, EMPEROR-Reduced studies proved a possibility of improving the outcomes for patients with HF with reduced LVEF irrespective of the presence or absence of DM2, thereby significantly expanding the potential target group for SGLT2is. EMPEROR-Preserved study is the only study of SGLT2is to date (the study drug ― empagliflozin) that has demonstrated high effectiveness of the drug in prevention of cardiovascular mortality and hospitalizations for HF, probably irrespective of LVEF and the existence of DM2. In result, on September 9, 2021, FDA (Food and Drug Administration, USА) assigned the “breakthrough therapy” status to Jardiance® (empagliflozin) drug for treatment of HF with preserved LFEF. EMPA-REG OUTCOME, DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, DAPA-CKD studies have shown SGLT2is to slow down the development of the terminal stage of chronic kidney disease. Finally, the main result of EMPULSE study completed in 2022, was the proven clinical benefit of empagliflozin in hospitalized and stabilized patients with acute HF decompensation irrespective of HF status and existence of DM2.

CONCLUSION: From the moment SGLT2is have been introduced in the clinical practice, they rapidly and successfully passed the way from the second-line antidiabetic drugs for which it was just enough not to worsen the prognosis for serious cardiovascular complications, to independent and effective class of drugs for treatment of HF (with class I and IIa recommendations). The totality of clinical trials of empagliflozin showed that empaflorizin is so far the only drug of the SGLT2is group with the proven safety and clinical effectiveness including the influence on the prognosis, in patients with HF irrespective of the LVEF status, presence or absence of DM2, for use in outpatient treatment and in stabilized patients in hospital.