Article Impact Level: HIGH Data Quality: STRONG Summary of JACC: CardioOncology, S2666087324004472. https://doi.org/10.1016/j.jaccao.2024.12.004 Danielle Medina-Hernández et al.
Points
- Researchers investigated the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, against anthracycline-induced cardiotoxicity (AIC) using a large animal model of 68 pigs.
- Pigs receiving doxorubicin were randomized into three groups: empagliflozin 20 mg, empagliflozin 10 mg, and a control group receiving doxorubicin alone.
- Empagliflozin significantly improved left ventricular ejection fraction (LVEF) in a dose-dependent manner, with the 20 mg group showing the highest LVEF (57.5%) compared to the control group (47.0%).
- No AIC events were observed in the 20 mg group, whereas 50% of the 10 mg group and 72% of the control group experienced AIC.
- Empagliflozin 20 mg improved ketone body utilization, preserved cardiac energetics, and enhanced mitochondrial function, indicating potential therapeutic benefits for mitigating AIC in clinical settings.
Summary
A study was conducted to investigate the potential cardioprotective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy, specifically empagliflozin, against anthracycline-induced cardiotoxicity (AIC) in a large animal model. The study used 36 large female White pigs to identify the most translational regimen for AIC, which involved six triweekly intravenous injections of doxorubicin (1.8 mg/kg each). A separate group of 32 pigs was randomized into four treatment arms: doxorubicin with empagliflozin 20 mg, doxorubicin with empagliflozin 10 mg, or doxorubicin alone (control). The pigs were followed for 21 weeks, during which multiparametric cardiac magnetic resonance and spectroscopy were used for serial examination, and metabolic and histological analyses were performed at the study’s conclusion.
The results demonstrated that empagliflozin significantly improved left ventricular ejection fraction (LVEF) in a dose-dependent manner. The median LVEF for the 20 mg empagliflozin group was 57.5% (Q1-Q3: 55.5%-60.3%), significantly higher than the 47.0% (Q1-Q3: 40.8%-47.8%) observed in the doxorubicin control group (P = 0.027). Additionally, the LVEF for the 10 mg empagliflozin group was 51% (Q1-Q3: 46.5%-55.5%, P = 0.020 vs. 20 mg group). The incidence of AIC events was 0% in the empagliflozin 20 mg group, 50% in the 10 mg group, and 72% in the control group. Furthermore, empagliflozin 20 mg treatment resulted in enhanced ketone body utilization by the myocardium, preserved cardiac energetics, and improved mitochondrial function, as evidenced by electron microscopy and respirometry. At the same time, these effects were less pronounced with the 10 mg dose.
In conclusion, the study supports that empagliflozin, an SGLT2 inhibitor, offers a dose-dependent cardioprotective effect against AIC, improving LVEF, myocardial metabolism, and mitochondrial function. These findings suggest the potential therapeutic benefits of empagliflozin in mitigating AIC in clinical settings.
Link to the article: https://www.sciencedirect.com/science/article/pii/S2666087324004472
References Medina-Hernández, D., Cádiz, L., Mastrangelo, A., Moreno-Arciniegas, A., Fernández Tocino, M., Cueto Becerra, A. A., Díaz-Guerra Priego, A., Skoza, W. A., Higuero-Verdejo, M. I., López-Martín, G. J., Pérez-Martínez, C., De Molina-Iracheta, A., Caballero-Valderrama, M., Sánchez-González, J., Sancho, D., Fuster, V., Galán-Arriola, C., & Ibáñez, B. (2025). Sglt2i therapy prevents anthracycline-induced cardiotoxicity in a large animal model by preserving myocardial energetics. JACC: CardioOncology, S2666087324004472. https://doi.org/10.1016/j.jaccao.2024.12.004
