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Randomized Controlled Trial
. 2024 Jun 28;23(1):224.
doi: 10.1186/s12933-024-02309-9.

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial

Shinya Fujiki #  1 , Kenichi Iijima #  2 , Yoshihisa Nakagawa  3 , Kazuyoshi Takahashi  4 , Masaaki Okabe  5 , Kengo Kusano  6 , Shingen Owada  7 , Yusuke Kondo  8 , Kenichi Tsujita  9 , Wataru Shimizu  10 , Hirofumi Tomita  11 , Masaya Watanabe  12 , Morio Shoda  13 , Masafumi Watanabe  14 , Takashi Tokano  15 , Toyoaki Murohara  16 , Takashi Kaneshiro  17 , Takeshi Kato  18 , Hidemori Hayashi  2 , Koji Maemura  19 , Shinichi Niwano  20 , Tomio Umemoto  21 , Hisako Yoshida  22 , Keiko Ota  23 , Takahiro Tanaka  24 , Nobutaka Kitamura  24 , Koichi Node  25 , Tohru Minamino  26   27   28 ; EMPA ICD investigators
Affiliations
Randomized Controlled Trial

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial

Shinya Fujiki et al. Cardiovasc Diabetol. .

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes.

Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values.

Results: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight.

Conclusions: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.

Keywords: Empagliflozin; Sodium-glucose cotransporter 2; Type 2 diabetes; Ventricular arrhythmia.

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Conflict of interest statement

S.F. received funding support of present manuscript from Nippon Boehringer Ingelheim Co. Ltd, Eli Lilly and Company. Y.N. received grant and speaking honoraria from Nippon Boehringer Ingelheim. K.K. received honoraria for lectures from Medtronic, Boehringer-Ingelheim. Y.K. received speaking honoraria from Biotronik Japan, Boston Scientific Japan, Daiichi-Sankyo, Bayer Yakuhin, Abbott Medical Japan, Japan Lifeline, and received research grant from Daiichi-Sankyo. K.Tsujita received scholarship fund from Boehringer Ingelheim Japan. W.S. received grant from Nippon Boehringer Ingelheim, Daiichi Sankyo Company, Ltd., and received speaking honoraria from Nippon Boehringer Ingelheim, Daiichi Sankyo Company, Ltd.,Bristol-Meyers Squibb, Bayer Yakuhin, Pfizer, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Johnson and Johnson KK, Medtronic Japan. H.T. received grant from Medtronic Japan Co., Ltd., Fukuda Denshi Kita-tohoku Hanbai Co., Ltd., BIOTRONIK Japan Co., Ltd., Japan Lifeline Co., and Boston Scientific Japan Co., Ltd., and received speaking honoraria from Boehringer Ingelheim. Masaya Watanabe received grant from Japan Society for the Promotion of Science and CASIO SCIENCE PROMOTION FOUNDATION. Masafumi Watanabe received grant from DAIICHI SANKYO COMPANY, LIMITED, CHUGAI PHARMACEUTICAL CO., LTD, Boston Scientific Corporation, Abbott Vascular Japan Co., Ltd, Cardinal Health, KANEKA MEDIX CORP, BIOTRONIK Japan, Inc, FUKUDA DENSHI, MEDTRONIC JAPAN CO., LTD, and received speaking honoraria from Otsuka Pharmaceutical Co., Ltd, DAIICHI SANKYO COMPANY, LIMITED, Nippon Boehringer Ingelheim Co., Ltd. T.Murohara received from Japan Boehringer Inc., Ono Pharmaceutical Inc., Daiichi- Sankyo Inc., AstraZeneca Inc. T.Kato received honoraria for lectures from Boehringer-Ingelheim, AstraZeneca, Ono Pharmaceutical, Medtronic, BIOTRONIK, Boston Scientific, Abbott. K.M. received grant from Daiichi-Sankyo, and received honoraria for lectures from Daiichi-Sankyo, Novartis, Takeda, Pfizer, Nippon Boehlinger ingelheim. K.N. received speaking honoraria from Astellas, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, Novo Nordisk Pharma, Novartis Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, MSD. T.Minamino received funding support for the present study, provision of study drugs and remuneration for lectures from Nippon Boehringer Ingelheim and Eli Lilly. K.I., K.Takahashi, M.O., S.O., M.S., T.Tokano, T.Kaneshiro, H.H., S.N., T.U., H.Y., K.O., T.Tanaka, N.K. declare no competing interests.

Figures

Fig. 1
Fig. 1
Enrollment and follow-up. All the patients who underwent randomization were included in the primary analysis
Fig. 2
Fig. 2
Changes in the number of ventricular arrhythmias before and after treatment. The figure shows the changes in the number of ventricular arrhythmias recorded by an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator from the 24 weeks before treatment (assessed at week 0) and to the 24 weeks during treatment (assessed at week 24) in the empagliflozin and placebo groups. P values were calculated by the generalized linear model to evaluate for significant differences in interactions between treatment group and period from baseline to week 24, which indicates a difference in the change of each variable over time between the empagliflozin and placebo groups
See this image and copyright information in PMC

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