The effects of empagliflozin on ventricular arrhythmias in heart failure patients with an implantable cardioverter-defibrillator: a systematic review

Background & Objectives Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has demonstrated cardiovascular benefits in heart failure (HF), but its effects on ventricular arrhythmias (VAs) and implantable cardioverter-defibrillator (ICD) therapies remain unclear. This systematic review evaluates the impact of empagliflozin on VA burden and ICD-related outcomes in HF patients. Methods A systematic search identified randomized controlled trials (RCTs) and observational studies assessing empagliflozin in HF patients with ICDs. Primary outcomes included ventricular arrhythmia episodes, appropriate ICD shocks, and anti-tachycardia pacing (ATP) therapy. Results Four studies (three RCTs, one retrospective) comprising 463 HF patients with reduced ejection fraction (HFrEF) were included. The EMPA-ICD trial (n=118) reported a 35% reduction in VA episodes over 24 weeks, with 18% of empagliflozin-treated patients experiencing VAs compared to 28% in the control group. Another study (n=220) found a 32% lower incidence of appropriate ICD shocks in the empagliflozin group (14% vs. 21%). ATP interventions were also reduced by 29% in empagliflozin-treated patients. Empagliflozin was also associated with improved heart rate variability parameters; a 22% reduction in late gadolinium enhancement on cardiac MRI, and lower serum biomarkers of myocardial fibrosis, including galectin-3 and ST2 as reported by EMPEROR-Preserved trial. Conclusions Empagliflozin is associated with a lower incidence of ventricular arrhythmias and ICD interventions in HF patients, suggesting a potential anti-arrhythmic benefit. Larger, long-term trials are needed to confirm these findings and elucidate underlying mechanisms.