Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery (EMPOAF), a randomized, double-blind, placebo-controlled trial
H Kakavand, M Aghakouchakzadeh, M Haghjoo, F Najafinezhad, F Yousefimoghaddam, B Hedayat, H Ghoshouni, E Kohansal, A Jalali, A Bozorgi, P Sadeghipour, K Hosseini, M Tajdini, P Mirzabeigi, A TalasazAbstract
Background
Postoperative atrial fibrillation (POAF) is among the most common arrhythmias in patients undergoing cardiac surgery and can complicate postoperative management. Empagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor and antidiabetic agent, may prevent POAF through multiple mechanisms.
Purpose
To evaluate the effect of empagliflozin versus placebo on the incidence of POAF in patients undergoing coronary artery bypass grafting (CABG).
Methods
The Empagliflozin to Prevent POAF (EMPOAF) trial is an investigator-initiated, interventional, double-blind, placebo-controlled, multicenter randomized controlled trial conducted at two tertiary teaching cardiology hospitals in Tehran, Iran. Patients scheduled for elective isolated CABG were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo, starting at least 3 days before surgery and continued until discharge (maximum: 30 days). Key exclusion criteria included a history of diabetes mellitus, atrial fibrillation, ketoacidosis, or recurrent urinary tract infections; severe renal or hepatic impairment; unstable hemodynamics; and prior use of SGLT2 inhibitors for another indication. The primary outcome was the incidence of POAF, defined as any adjudicated, documented atrial fibrillation or atrial flutter lasting ≥30 seconds following CABG, detected by 72-hour Holter ECG monitoring. Key secondary endpoints were the composite of life-threatening arrhythmias, postoperative acute kidney injury, length of hospitalization, in-hospital mortality, ischemic stroke, and systemic embolization. Key safety endpoints were life-threatening and/or genitourinary tract infections, hypoglycemia, and euglycemic ketoacidosis.
Results
Among 500 randomized patients, 467 were included in the primary analysis. The mean age of the study population was 61.3 ± 9.0 years, and 87.2% were male. POAF occurred in 30 patients (12.9%) in the empagliflozin group and 63 patients (26.8%) in the placebo group (odds ratio, 0.40; 95% confidence interval, 0.25–0.65; P < 0.001). Life-threatening arrhythmias occurred in 3 patients in the empagliflozin group and 7 patients in the placebo group (P = 0.33). There were no statistically significant differences between groups in genitourinary tract infections, life-threatening infections, in-hospital mortality, length of hospitalization, or acute kidney injury. No cases of ischemic stroke, systemic embolization, or euglycemic ketoacidosis were reported in either group.
Conclusions
In patients undergoing elective isolated CABG, empagliflozin significantly reduced the risk of POAF. Perioperative administration of empagliflozin in non-diabetic patients was safe.