Key result
Prophylactic empagliflozin, with or without perindopril, improved left ventricular ejection fraction (66±3% and 67±4% vs 40±4%) in mice with chemotherapy-induced cardiotoxicity.
Why the study?
Doxorubicin and trastuzumab improve breast cancer survival but increase heart failure risk, and the cardioprotective efficacy of prophylactic empagliflozin with or without perindopril was largely unexplored.
Does prophylactic empagliflozin with or without perindopril prevent doxorubicin and trastuzumab-mediated cardiotoxicity in a murine model?
Does prophylactic empagliflozin with or without perindopril prevent doxorubicin and trastuzumab-mediated cardiotoxicity in a murine model?
Prophylactic administration of empagliflozin, with or without perindopril, mitigates adverse cardiovascular remodeling and preserves LVEF in a murine model of chemotherapy-induced cardiotoxicity.
Hypothesis-generating for prophylactic empagliflozin to prevent HF from doxorubicin-trastuzumab; prospective trials needed before clinical adoption.
Background/Objectives: While doxorubicin (DOX) and trastuzumab (TRZ) improve overall survival in women with breast cancer, these two anti-cancer drugs increase the risk of developing heart failure. As a novel and largely unexplored approach, our aim was to evaluate whether the prophylactic use of the sodium-glucose co-transporter 2 inhibitor empagliflozin (EMPA), with and without the angiotensin converting enzyme inhibitor perindopril (PER), is cardioprotective in preventing DOX + TRZ-mediated cardiotoxicity. Methods: In a chronic in vivo murine model, female mice received prophylactic treatment with PER (3 mg/kg), EMPA (10 mg/kg), or EMPA + PER via oral gavage for a total of 3 weeks as a run-in period prior to weekly administration of DOX + TRZ (8 mg/kg and 3 mg/kg, respectively) intraperitoneally for an additional 3 weeks (total of 6 weeks). Results: In mice treated with DOX + TRZ, the left ventricular ejection fraction (LVEF) decreased from 75 ± 2% at baseline to 40 ± 4% at week 6. Prophylactic treatment with either PER, EMPA, or EMPA+PER improved LVEF to 58 ± 3%, 66 ± 3%, and 67 ± 4% at week 6, respectively (p < 0.05). Histological analyses confirmed significant disruption of myofibrils, vacuolization, and loss of sarcomere integrity in the DOX + TRZ-treated mice. Prophylactic administration with PER, EMPA, or EMPA + PER, however, improved myofibril integrity at week 6 in mice receiving DOX + TRZ. Finally, although the Bax/Bcl-xL ratio was significantly elevated by 1.5-fold in mice treated with DOX + TRZ, this marker of apoptosis was attenuated by prophylactic treatment with either PER, EMPA, or EMPA + PER. Conclusions: Prophylactic administration of EMPA mitigated adverse cardiovascular remodeling in a chronic in vivo model of DOX + TRZ-mediated cardiotoxicity.
No takes yet. Share an insight, caveat, or question.
Rozovsky et al. (2026) studied this question. Prophylactic empagliflozin, with or without perindopril, improved left ventricular ejection fraction (66±3% and 67±4% vs 40±4%) in mice with chemotherapy-induced cardiotoxicity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: