Effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on vascular function in patients with chronic heart failure

Aims Impairment of vascular function contributes to the progression of chronic heart failure (HF) by increasing the afterload. Treatment with selective sodium-glucose cotransporter 2 (SGLT2) inhibitors improves the prognosis of HF, but the precise mechanisms remain unclear. The aim of this study was to analyse the effect of empagliflozin on vascular function in patients with HF. Methods and results In an investigator initiated, double-blind, randomized, placebo-controlled, parallel-group, clinical study, patients with HF NYHA II-III and an ejection fraction of 49% or less were randomized 2:1 to receive empagliflozin 10 mg once daily or placebo for 3 months. A total of 74 patients (15% female), aged 66 +/- 9 years, with a mean ejection fraction of 39 +/- 8% and a median NTproBNP of 558 pg/mL (IQR 219-1051 pg/ml), were included. Vascular parameters such as central systolic blood pressure (cSBP), central pulse pressure (cPP), forward (FPH), and reflected pressure pulse height (RPH) decreased under resting conditions after 1 and 3 months (1 month: cSBP -6.4 +/- 8.3 mmHg, P < 0.001, cPP -3.0 +/- 6.6 mmHg, P = 0.004, FPH -2.5 +/- 4.5 mmHg, P = 0.001, RPH -1.6 +/- 3.0 mmHg, P = 0.001; 3 months: cSBP -4.6 +/- 8.4 mmHg, P = 0.001, cPP -3.1 +/- 4.8 mmHg, P < 0.001, FPH -1.7 +/- 3.7 mmHg, P = 0.004, RPH -1.4 +/- 2.5 mmHg, P = 0.001) in patients treated with empagliflozin (n = 45). In accordance, cSBP and cPP decreased in patients with empagliflozin treatment under 24 h ambulatory conditions after 1 and 3 months (1 month: cSBP -4.8 +/- 10.1 mmHg, P = 0.003, cPP -2.0 +/- 5.7 mmHg, P = 0.026; 3 months: cSBP -4.7 +/- 9.0 mmHg, P = 0.002, cPP -2.1 +/- 6.4 mmHg, P = 0.044). In the placebo group, there was no significant change after 1 and 3 months. The decrease in cSBP under resting conditions (-5.7 +/- 2.4 mmHg, P = 0.019) after 1 month and in cSBP (-6.0 +/- 2.6, P = 0.027) as well as in pulse wave velocity (-0.5 +/- 0.2 m/s, P = 0.021) under 24 h ambulatory conditions after 3 months was greater in the empagliflozin group than in the placebo group. Conclusions We found an improvement of vascular function after treatment with empagliflozin that indicates decreased afterload of the left ventricle and may contribute to the beneficial effects of SGLT2 inhibition in HF.