In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

Arturo Cesaro, Felice Gragnano, Pasquale Paolisso, Luca Bergamaschi, Emanuele Gallinoro, Celestino Sardu, Niya Mileva, Alberto Foà, Matteo Armillotta, Angelo Sansonetti, Sara Amicone, Andrea Impellizzeri, Giuseppe Esposito, Nuccia Morici, Jacopo Andrea Oreglia, Gianni Casella, Ciro Mauro, Dobrin Vassilev, Nazzareno Galie, Gaetano Santulli, Carmine Pizzi, Emanuele Barbato, Paolo Calabrò, Raffaele Marfella, Arturo Cesaro, Felice Gragnano, Pasquale Paolisso, Luca Bergamaschi, Emanuele Gallinoro, Celestino Sardu, Niya Mileva, Alberto Foà, Matteo Armillotta, Angelo Sansonetti, Sara Amicone, Andrea Impellizzeri, Giuseppe Esposito, Nuccia Morici, Jacopo Andrea Oreglia, Gianni Casella, Ciro Mauro, Dobrin Vassilev, Nazzareno Galie, Gaetano Santulli, Carmine Pizzi, Emanuele Barbato, Paolo Calabrò, Raffaele Marfella

Abstract

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients.

Objectives: To investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).

Methods: Patients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization.

Results: The study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%, p = 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14-0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04-0.97; p = 0.046) but not of AF occurrence.

Conclusions: In T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control.

Trial registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

Keywords: acute myocardial infarction; atrial fibrillation; hyperglycemia; sodium-glucose cotransporter 2 inhibitors (SGLT2-i); ventricular arrhythmias; ventricular tachycardia.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Cesaro, Gragnano, Paolisso, Bergamaschi, Gallinoro, Sardu, Mileva, Foà, Armillotta, Sansonetti, Amicone, Impellizzeri, Esposito, Morici, Oreglia, Casella, Mauro, Vassilev, Galie, Santulli, Pizzi, Barbato, Calabrò and Marfella.

Figures

Figure 1
Figure 1
Study design and occurrence of new-onset cardiac arrhythmias. AF, atrial fibrillation; AMI, acute myocardial infarction; NOCAs, new-onset cardiac arrhythmias; T2DM, type 2 diabetes mellitus; SGLT2-i, Sodium-glucose co-transporter 2 inhibitors; VF, Ventricular Fibrillation; VT, Ventricular Tachycardia.
Figure 2
Figure 2
Primary endpoint and its individual components in SGLT2-i and non-SGLT2-i users. AF, atrial fibrillation; NOCAs, new-onset cardiac arrhythmias; SGLT2-i, Sodium-glucose co-transporter 2 inhibitors; VF, Ventricular Fibrillation; VT, Ventricular Tachycardia.
Figure 3
Figure 3
Effects of predictors of new-onset cardiac arrhythmias. BGL, blood glucose level; CA, cardiac arrest; ECG, electrocardiogram; LVEF, Left ventricular ejection fraction; NOCAs, new-onset cardiac arrhythmias; SGLT2-i, Sodium-glucose cotransporter 2 inhibitors; STEMI, ST-elevation myocardial infarction; VT, ventricular tachycardia.

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