Effect of Empagliflozin Versus Placebo on Plasma Volume Status in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus

Abstract

Introduction: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (1:1) to receive 10 mg empagliflozin or a placebo (once daily), 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24. Results: Overall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9 years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24 weeks (-2.2 vs. ? 0.1 kg, P \ 0.001, and -5.1 vs. -0.3%, P \ 0.001, respectively). Decreased PVS, defined as a change in PVS of \ -4.5%, was associated with the administration of empagliflozin (odds ratio 2.61, 95% confidence interval 1.11-6.15, P = 0.028). N-terminal pro b-type natriuretic peptide levels decreased in both the empagliflozin and placebo groups (1028.7-370.3 pg/mL, P \ 0.001, and 1270.6-673.7 pg/mL, P \ 0.01, respectively). Conclusion: Empagliflozin reduced the body weight and PVS. Early SGLT2 inhibitor administration in patients with AMI, CHF, and T2DM

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

“…On the basis of a comprehensive review, we identified 15 studies that evaluated the effect of SGLT2 inhibitors on plasma volume (Table 2). 64,[72][73][74]78,[98][99][100][101][102][103][104][105][106][107][108][109] Unfortunately, most studies estimated changes in plasma volume using the Kaplan-Hakim and Strauss formulae, which cannot be applied to the evaluation of changes produced by SGLT2 inhibitors. Four reports 64,72,74,109 used indicator dilution methods, and of these, 3 were double blind and placebo controlled.…”

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

“…Life 2022, 12, 2062 3 of 16 Among subjects with established HFrEF, treatment with an SGLT-2 inhibitor compared to placebo resulted in a significant decrease in estimated extracellular volume and estimated plasma volume after 12 weeks [25]. In addition, early treatment with an SGLT-2 inhibitor in subjects with a recent acute myocardial infarction, pre-existing T2DM and established HF was shown to produce a significant decrease in plasma volume status after long-term treatment, equal to 24 weeks [26].…”