Abstract
THE FAVOURABLE EFFECTS OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN CHRONIC HEART FAILURE PATIENTS - THE FOURTH PILLAR OF HEART FAILURE MANAGEMENT

Nabil Naser*, Azra Durak - Nalbantic, Esad Pepic, Mirsad Selimovi?, Zelija Velija-Ašimi, Edin Begi?

ABSTRACT

Background: The current global prevalence of heart failure is estimated at 64.34 million cases and 9.91 million years of disability as a result. Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. Objective: The aim of our study was to determine whether Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are useful for treating patients with chronic heart failure and their clinical benefits, especially their effect on preventing hospitalization due to worsening heart failure, reducing mortality, improving clinical status and quality of life among patients with heart failure. Methods: From March 2021 to May 2022, 126 randomized patients with chronic heart failure with reduced ejection fraction (HFrEF) were prospectively enrolled. Patients treated with standard optimal medical therapy and SGLT2 inhibitor empagliflozin were compared with an arm of the same size and matched by age and gender patients who were taking only a standard optimal medical therapy for HFrEF. Results: The mean duration of follow-up in the two treatment arms was 12 months. In the (SOMT + SGLT2i) arm, we evaluated the hemodynamic, metabolic, renal, and cardiac remodeling parameters upon initial evaluation and at the end of the follow-up after 12 months of treatment. A 6.3% increase in LVEF value was observed with SOMT + SGLT2i compared to SOMT alone (p < 0.001). Only the SOMT + SGLT2i treatment arm had significant improvement in LVMi from baseline with a mean reduction of -8,3g/m2. A reduction of -7.0 mL/m2 in LVESV index was observed in the first group treated with SOMT and SGLT2i compared to the SOMT arm (p < 0.001). LVEDV index was reduced by -9.5 mL/m2 with empagliflozin (p < 0.001). Th mean reduction in LAVi was - 4.1 mL/m2 (p < 0.001). In in the arm treated with SOMT + SGLT2i thew FMR (≥ II Grade) was reduced by -11% (p < 0.001). The values of systolic blood pressure, blood glucose and HbA1c decreased significantly in the SOMT + SGLT2i arm compared to the second arm (127.4 vs. 1121.1 mmHg, 6.4 vs. 5.6 mmol/L and 6.3 vs. 5.4 %) respectively; p < 0.001). The eGFR values increased considerably in the SOMT + SGLT2i arm compared to the SOMT arm by 9.7 mL/min/1.73 m2; (p < 0.001). A significant reduction of 2492.8 (pg/mL) in NT-pro-BNP levels was observed only in the SOMT + SGLT2i arm (p < 0.001). Over the course of one year, the mean KCCQ total symptom score increased 2.8 points more in the SOMT + SGLT2i group than in the SOMT group. In the arm SOMT + SGLT2i, the composite of cardiovascular death or worsening heart failure was lower in comparison with the control group (20.1 vs. 29.1%; P<0.001). There was a lower rate of worsening heart failure in the SOMT + SGLT2i arm compared to the SOMT group (15.1 vs 20.2%; P<0.001). Compared to the SOMT arm, the arm treated with SOMT + SGLT2i had a lower cardiovascular death rate (14.6 vs. 19.9%; P<0.001). Conclusion: Our study has demonstrated favourable changes on cardiac remodeling parameters (LVEF, LVMi, LVEDVi, LVESVi, LAVi), lower rate of hospitalization and cardiovascular death. When empagliflozin is administered to diabetic and nondiabetic HFrEF patients, LV volumes, LV mass, LV systolic function, functional capacity, and quality of life are significantly improved. A favourable reverse remodeling of the LV may explain the reduction in heart failure hospitalizations and mortality caused by SGLT2 inhibitors. In HFrEF patients, SGLT2 inhibitors are strongly recommended in guidelines. SGLT2 inhibitors have become a fourth pillar of chronic heart failure management based on the collective data of their efficacy.

Keywords: Chronic heart failure, Sodium-glucose transporter 2 inhibitors (SGLT2i), Heart failure with reduced ejection fraction (HFrEF).


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