Efficacy and safety of empagliflozin to reduce atrial fibrillation episodes: systematic review

Atrial fibrillation (AF) is a prevalent arrhythmia with significant morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, like empagliflozin, have demonstrated cardioprotective benefits, but their specific efficacy for reducing AF episodes has not been systematically evaluated. This systematic review aimed to synthesize the existing evidence on the efficacy and safety of empagliflozin for reducing atrial fibrillation episodes across various patient populations. A comprehensive search was conducted from 2020 to 2025, following PRISMA guidelines. Studies that assessed the impact of empagliflozin on AF incidence, recurrence, burden, or post-operative AF (POAF). Six studies were included, indicating that empagliflozin significantly reduce the composite risk of cardiovascular death or heart failure hospitalization in patients with and without pre-existing AF, with a larger absolute benefit in high-risk AF subgroups. For specific AF outcomes, a trend towards reduced POAF was observed, alongside a significant reduction in post-operative ventricular arrhythmias and inflammation. One real-world study suggested a potential difference in AF efficacy within the SGLT2 inhibitor class, favoring dapagliflozin. The safety profile of empagliflozin was consistent with its known pharmacology and was not associated with increased serious adverse events, even in surgical populations. The empagliflozin demonstrated a beneficial effect on reducing AF-related complications, primarily driven by its profound impact on heart failure outcomes. Emerging evidence suggests a role in primary AF prevention, potentially mediated through anti-inflammatory, anti-fibrotic, and hemodynamic mechanisms. While the overall safety profile is favorable, questions regarding comparative efficacy within the SGLT2 inhibitor class remain.