Effects of Empagliflozin Versus Placebo on Cardiac Sympathetic Activity in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: The EMBODY Trial

Abstract

Background: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity.Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and T2DM in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency–to–high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT.Results: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were +11.6 and +9.1 msec in the empagliflozin (P=0.02) and placebo groups (P=0.06), respectively. Change in LF/HF ratio was –0.57 and –0.17 in the empagliflozin (P=0.01) and placebo groups (P=0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P=0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed.Conclusions: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2D and AMI. Early SGLT2 inhibitor administration in AMI patients with diabetes mellitus might be effective in improving cardiac nerve activity without any adverse events.Trial Registration: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442

Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value

“…123 Early SGLT2 inhibitor administration in patients with acute myocardial infarction and T2DM can improve cardiac nerve activity without any adverse events. 124 These results suggest that SGLT2 inhibitors may exert a reverse ventricular remodeling effect by inhibiting the RAS. We look forward to the EMPYREAN study, which aims to study the impact of empagliflozin on sympathetic and parasympathetic nerve activity in patients with T2DM.…”

Effect of sodium‐glucose cotransporter‐2 inhibitors on myocardial infarction incidence: A systematic review and meta‐analysis of randomized controlled trials and cohort studies

“…The EMBODY and EMMY trials ascertained that early initiation and sustained administration of SGLT2 inhibitors in acute MI patients correlated with a markedly enhanced reduction in N‐terminal prohormone of brain natriuretic peptide levels, amelioration of cardiac nerve activity, and improvement in echocardiographic functional and structural parameters 15,16 . Nonetheless, the influence of SGLT2 inhibitors on MI incidence remains ambiguous.…”