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

Cardiovascular Diabetology

Mitsunori Maruyama¹  Masahiro Ishikawa¹  Yasushi Miyauchi²  Eitaro Kodani³  Masaaki Miyamoto⁴  Shuhei Tara⁴  Kosuke Mozawa⁴  Yu Hoshika⁴  Yoshiaki Kubota⁴  Kuniya Asai⁴  Hitoshi Takano⁴  Wataru Shimizu⁴  Yukichi Tokita⁴  Yayoi Tsukada⁴  Yu-ki Iwasaki⁴  Kenji Yodogawa⁴  Takeshi Yamamoto⁴  Michio Ogano⁵  Jun Tanabe⁵ 

[1] Department of Cardiovascular Medicine, Nippon MEDICAL School Musashi Kosugi Hospital, Tokyo, Japan;Department of Cardiovascular Medicine, Nippon Medical School Chiba Hokuso Hospital, Chiba, Japan;Department of Cardiovascular Medicine, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan;Department of Cardiovascular Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, 113-0022, Tokyo, Japan;Department of Cardiovascular Medicine, Shizuoka Medical Center, Shizuoka, Japan;

关键词: Acute Myocardial Infarction;    Heart rate variability;    Heart rate turbulence;    Sodium–glucose cotransporter 2 inhibitor;    Sudden cardiac death;    Randomized Controlled Trial;   

DOI  :  10.1186/s12933-020-01127-z

来源: Springer

【 摘 要 】

BackgroundProtection 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.MethodsThis 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.ResultsOverall, 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.ConclusionsThis 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.

【 授权许可】

CC BY