Objective: This study aimed to compare the effects of empagliflozin and dapagliflozin on classical lipid parameters—including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)—as well as on atherogenic risk indices, including the atherogenic index of plasma (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), atherogenic coefficient (AC), and triglyceride-glucose index (TyG), in patients with heart failure and a history of coronary artery bypass grafting (CABG). To our knowledge, this is the first study to comprehensively evaluate these parameters in this high-risk population. Methods: This single-center, retrospective study included 484 patients with preserved ejection fraction heart failure and prior CABG who were treated with sodium–glucose cotransporter-2 (SGLT2) inhibitors. Patients were allocated to empagliflozin (n = 201) or dapagliflozin (n = 283) groups. All patients were receiving statin therapy. Lipid parameters and atherogenic indices were evaluated at baseline and after 12 weeks of treatment. Results: Both empagliflozin and dapagliflozin significantly reduced TC and LDL-C at 12 weeks (p < 0.001). No significant changes were observed in HDL-C or TG. Both agents produced significant improvements in CRI-I, CRI-II, AC, and TyG index (all p < 0.001), while AIP remained unchanged. Dapagliflozin achieved a greater reduction in TC (p = 0.044). Conclusions: This study represents the first direct comparison of empagliflozin and dapagliflozin on lipid profiles and atherogenic indices in patients with heart failure and prior CABG. Both agents significantly improved TC, LDL-C, and atherogenic indices. Dapagliflozin achieved a greater reduction in TC compared with empagliflozin, but overall both drugs demonstrated favorable and largely comparable effects. Beyond improvements in absolute values, both agents also contributed to favorable shifts in risk categories of lipid-derived indices. These findings suggest that clinical decision-making between empagliflozin and dapagliflozin may rely on factors other than lipid modulation. Larger multicenter prospective trials are warranted to confirm these results and clarify their long-term cardiovascular implications.

Background: Empagliflozin and dapagliflozin are the most widely prescribed sodium–glucose cotransporter-2 inhibitors (SGLT2i) with established cardioprotective benefits across the spectrum of heart failure (HF). However, direct comparative data remain limited, particularly in patients with a history of coronary revascularization—a population at persistently high cardiovascular (CV) risk. This study aimed to compare the long-term cardiovascular outcomes of empagliflozin versus dapagliflozin in revascularized HF patients who had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Methods: This retrospective cohort study included 631 HF patients who had undergone coronary revascularization (CABG or PCI) and were treated with an SGLT2 inhibitor (353 dapagliflozin, 278 empagliflozin) between 2014 and 2022 at a tertiary cardiovascular center. Patients were stratified by left ventricular ejection fraction (LVEF ≥ 50%: HFpEF; LVEF < 50%: HFrEF/HFmrEF). The primary outcomes were all-cause mortality, cardiac mortality, major adverse cardiovascular events (MACE), cardiac MACE, and HF-related hospitalization. Cox regression analyses—including time-dependent covariates—were performed to identify independent predictors of cardiac MACE. Results: Baseline demographic, clinical, and biochemical characteristics were comparable between groups. During a mean follow-up of 19.6 ± 1.5 months, there were no significant differences between dapagliflozin and empagliflozin in all-cause mortality (19.3% vs. 19.8%), cardiac mortality (11.0% vs. 12.2%), MACE (25.8% vs. 26.3%), cardiac MACE (23.8% vs. 21.9%), or hospitalization (23.8% vs. 23.7%) (all p > 0.05). Subgroup analyses by LVEF yielded consistent findings. In time-adjusted Cox modeling, age (HR = 2.089; 95% CI: 1.723–2.533; p < 0.001) and atrial fibrillation (AF) (log-rank p = 0.030) were identified as significant predictors of cardiac MACE, while creatinine and NT-proBNP lost significance after adjustment. Both age and AF showed time-varying hazard effects, with risk attenuation over time. Conclusions: In this real-world cohort of revascularized HF patients, empagliflozin and dapagliflozin demonstrated comparable long-term cardiovascular outcomes, supporting a class effect of SGLT2 inhibitors in this high-risk population. Beyond pharmacologic comparison, age and AF emerged as dynamic predictors of cardiac MACE, highlighting the importance of longitudinal, time-dependent risk assessment in heart failure management following coronary revascularization.