New principles for the treatment of chronic heart failure: the phenomenon of sodium-glucose cotransporter type 2 inhibitors

Abstract

Chronic heart failure (CHF) is one of the most important problems in clinical cardiology due to high morbidity, frequent hospitalizations and poor prognosis of patients. Quite unexpectedly, sodium-glucose cotransporter type 2 (SGLT2i) inhibitors dapagliflozin and empagliflozin, which were created for the treatment of diabetes mellitus, proved to be effective means of reducing the risk of an adverse outcome in patients with CHF, they were included in a new four-component therapy for CHF with a reduced left ventricular ejection fraction with a class of recommendations I and level of evidence A. The basis for changing the clinical guidelines for CHF was the results of large randomized trials of DAPA-HF and EMPEROR-Reduced. Despite the obvious clinical benefit of using SGLT2i in CHF, the mechanisms of the observed effects remain speculative and continue to be actively studied. In particular, the literature discusses the role of osmotic diuresis, lowering blood pressure and body weight, increasing erythropoietin production, influencing myocardial remodeling, modifying the energy metabolism of the heart, inhibiting the sodium-hydrogen exchanger, autophagy, and influencing leptin and adiponectin levels. SGLT2i has many of the qualities of an ideal agent for the treatment of CHF with reduced left ventricular ejection fraction, including a single dose without the need for titration, once daily administration, early positive effects on clinical outcomes and quality of life, a favorable safety and tolerability profile with a frequency of serious side effects not different from placebo. At the same time, the choice of medical tactics may be influenced by the features of the evidence base of SGLT2i, in particular, the reduction in cardiovascular mortality and death from any cause in a randomized trial of dapagliflozin.