SIMVASTATIN as a potential protective strategy against doxorubicin-induced cardiotoxicity

Background: Doxorubicin-induced cardiotoxicity (DIC) represents a major limitation in oncology, leading to ventricular dysfunction and long-term morbidity. Lipophilic statins, such as simvastatin, exert pleiotropic effects beyond cholesterol lowering, including antioxidant and anti-inflammatory actions, which may confer cardioprotection. Methods: We retrospectively analyzed 80 oncology patients treated with anthracycline-based chemotherapy. Clinical, biochemical, and electrocardiographic (ECG) data were collected at baseline and after completion of chemotherapy or during follow-up. Early chemotherapy-related cardiac dysfunction was assessed using ECG markers, including QTa/QTc prolongation and T-wave flattening. Reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) < 50%. Patients were stratified according to exposure to simvastatin therapy versus no statin treatment. Associations between statin use and cardiac outcomes were evaluated using adjusted regression models; additional propensity score-based weighting analyses were performed to account for potential baseline differences between groups. Results: Seven patients developed HFrEF. Among patients with preserved LVEF (>60%), 25 developed new ECG abnormalities, whereas 39 maintained normal ECG findings. Statin therapy was strongly associated with protection against ECG alterations: 23 of 25 patients with ECG changes were not receiving statins, while 33 of 39 patients without abnormalities were statin users. Statin-treated patients showed significantly smaller declines in LVEF (ΔLVEF -1.7% vs. -8.0%, p = 0.0017) and reduced prolongation of ventricular repolarization intervals (ΔQT and ΔQTc) compared with non-users. In adjusted analyses, simvastatin exposure remained independently associated with preservation of systolic function and attenuation of QT/QTc prolongation. Statin-treated patients also exhibited lower total and low-density lipoprotein (LDL) cholesterol levels, consistent with expected pharmacologic effects. No clinically relevant differences were observed in atrioventricular or intraventricular conduction parameters. Propensity score-weighted analyses confirmed the robustness of the association between statin therapy and reduced risk of electrocardiographic abnormalities. Conclusion: Statin therapy was associated with a lower incidence of early electrocardiographic abnormalities and attenuation of subclinical cardiac dysfunction in patients treated with doxorubicin. These findings suggest that lipophilic statins may mitigate early electrophysiological remodeling and preserve ventricular function during anthracycline therapy, supporting a potential cardioprotective role beyond lipid lowering.