Impact of Dapagliflozin Treatment on Serum Sodium Concentrations in Acute Heart Failure

Abstract

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown.

Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia.

Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [-2; 4] mmol/L), as compared to the control group (-1 [-3.75; 2]); p < 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [-3; 3.75] mmol/L vs. -2 [-4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008).

Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization.

Keywords: Acute heart failure; Dapagliflozin; Hyponatremia.