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Open Access 01-12-2020 | Sudden Cardiac Death | Original investigation

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

Authors: Wataru Shimizu, Yoshiaki Kubota, Yu Hoshika, Kosuke Mozawa, Shuhei Tara, Yukichi Tokita, Kenji Yodogawa, Yu-ki Iwasaki, Takeshi Yamamoto, Hitoshi Takano, Yayoi Tsukada, Kuniya Asai, Masaaki Miyamoto, Yasushi Miyauchi, Eitaro Kodani, Masahiro Ishikawa, Mitsunori Maruyama, Michio Ogano, Jun Tanabe, EMBODY trial investigators

Published in: Cardiovascular Diabetology | Issue 1/2020

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 type 2 diabetes mellitus (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 ms 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 T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM 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.

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Title: Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial
Authors: Wataru Shimizu
Yoshiaki Kubota
Yu Hoshika
Kosuke Mozawa
Shuhei Tara
Yukichi Tokita
Kenji Yodogawa
Yu-ki Iwasaki
Takeshi Yamamoto
Hitoshi Takano
Yayoi Tsukada
Kuniya Asai
Masaaki Miyamoto
Yasushi Miyauchi
Eitaro Kodani
Masahiro Ishikawa
Mitsunori Maruyama
Michio Ogano
Jun Tanabe
EMBODY trial investigators
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Sudden Cardiac Death
Empagliflozin
Myocardial Infarction
Diabetes
Type 2 Diabetes
Published in: Cardiovascular Diabetology / Issue 1/2020
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-020-01127-z

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