SGLT2is and Risk Reduction of Atrial Arrhythmias SCD in Patients with CIED

Patients with cardiac implantable electronic devices (CIED) who received SGLT2is had a significantly lower incidence of atrial arrhythmia (AA) compared to placebo. 

Heart failure (HF), sudden cardiac death (SCD), and arrhythmias remain important causes of mortality in patients with type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are FDA-approved novel classes of oral hypoglycemic medications to treat type 2 diabetes mellitus (T2DM). However, recent evidence based on several randomized clinical trials has suggested their possible role as a new foundational therapy to prevent hospitalizations and death from heart failure (HF). For example, the EMPA-REG OUTCOME trial, with over 7000 diabetes patients, showed that patients with T2DM who received the SGLT2i, Jardiance (empagliflozin, Boehringer Ingelheim and Eli Lilly), in addition to standard of care, had a lower rate of the primary composite cardiovascular outcome and death from any cause compared to placebo. These findings have led to the FDA’s recent approval of Jardiance to treat patients with heart failure with reduced ejection fraction (HFrEF).  

Several other studies investigated other beneficial hemodynamic effects of SGLT2, including a recent study by Goldenberg I et al., which suggested an association between SGLT2i (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) in patients with type 2 diabetes mellitus (T2DM) or HF and atrial or ventricular arrhythmias, including patients with cardiac implantable electronic devices (CIEDs). Of the 13,890 patients who received a CIED and were enrolled in the study, 898 (6%) received an SGLT2i (dapagliflozin, empagliflozin, canagliflozin), and atrial and ventricular arrhythmic events were registered over five years. At baseline, patients receiving an SGLT2i had a higher prevalence of diabetes, ischemic cardiomyopathy, and prior heart failure. However, the prevalence of atrial fibrillation (AFib) was similar in both groups. A recent clinical trial examined the favorable cardiovascular outcomes of SGLT2 inhibitors in HF patients with cardiovascular death and hospitalization for heart failure (HHF) as the primary endpoint.  

The study showed a consistent 23% risk reduction of AA (HR, 0.77; P<0.001) and a 44% risk reduction in all-cause mortality (HR, 0.56; P=0.001). The mechanism responsible for the antiarrhythmic effects of SGLT2is is not fully understood but is assumed to be due to their rule on structural, electromechanical, and mechanical myocardial remodeling. The study concluded that SGLT2 inhibitors could be linked with hemodynamic changes, including a lowered intracardiac filling pressure, reduced arterial stiffness, and a higher hematocrit leading to a decrease in AA in patients with CIED. 

Practice Pearls: 

• SGLT2 inhibitors have been shown to have beneficial hemodynamic effects in patients with T2DM and cardiac implantable electronic devices.  
• The risk reduction of AA and all-cause mortality was significantly lower among patients who received an SGLT2 inhibitor than those who received a placebo. 
• SGLT2is’ AA effect could be linked to hemodynamic changes, including a lowered intracardiac filling pressure, reduced arterial stiffness, and a higher hematocrit in patients with CIED. 

References for “SGLT2is and Risk Reduction of Atrial Arrhythmias SCD in Patients with CIED”:
Goldenberg I, et al. Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Atrial Arrhythmia Burden in Patients with Cardiac Implantable Electronic Devices. FS.07, AHA 2021 Scientific Sessions, 13-15 November. 

Hu, Z., Ju, F., Du, L. et al. Empagliflozin protects the heart against ischemia/reperfusion-induced sudden cardiac death. Cardiovasc Diabetol 20, 199 (2021). https://doi.org/10.1186/s12933-021-01392-6 

Butler J, Usman MS, Khan MS, et al. Efficacy and safety of SGLT2 inhibitors in heart failure: systematic review and meta-analysis [published correction appears in ESC Heart Fail. 2021 Jun;8(3):2362]. ESC Heart Fail. 2020;7(6):3298-3309. doi:10.1002/ehf2.13169 

Elmoataz Elmamou, PharmD Candidate, 2022, South College School of Pharmacy