Effect of Empagliflozin Versus Placebo on Cardiac Sympathetic Activity in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Rationale

Abstract

Introduction: Protection from lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important problems after myocardial infarction. Cardiac sympathetic hyperactivity is related to poor prognosis and fatal arrhythmias and can be non-invasively assessed with heart rate variability, heart rate turbulence, T-wave alternans, late potentials, and ¹²³I-meta-iodobenzylguanide (¹²³I-MIBG) scintigraphy. Sodium glucose cotransporter 2 (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is augmented in part due to the stimulatory effect of hyperglycemia. The EMBODY trial is designed to determine whether the suppression of cardiac sympathetic activity induced by the SGLT2 inhibitor is accompanied by protection against adverse cardiovascular outcomes.

Methods: The EMBODY trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with acute MI and type 2 diabetes in Japan. A total of 98 patients will be randomized (1:1) to receive once-daily placebo or empagliflozin, an SGLT2 inhibitor, 10 mg. The primary end point is the change from baseline to 24 weeks in heart rate variability. Secondary end points include the change from baseline for other sudden cardiac death surrogate-markers such as heart rate turbulence, T-wave alternans, late potentials, and ¹²³I-MIBG scintigraphy imaging. Adverse effects will be evaluated throughout the trial period.

Planned outcomes: The EMBODY trial will evaluate the potential cardioprotective effect of empagliflozin and will provide additional important new data regarding its preventative effects on sudden cardiac death.

Trial registration: Unique Trial Number, UMIN000030158 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034442 ).

Funding: Nippon Boehringer Ingelheim and Eli Lilly and Company.

Keywords: Acute myocardial infarction; Cardiac sympathetic activity; Empagliflozin, sodium glucose cotransporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus (T2DM).

Fig. 1

Trial outline. Patients with acute myocardial infarction and type 2 diabetes mellitus will be randomly assigned to receive empagliflozin (10 mg/day) or placebo add-on to conventional therapy at 2 weeks after the onset of AMI. They will receive treatment for 24 weeks after stratified randomization