Anthracyclines and the heart: A double-edged sword with therapeutic hopes

Background: Anthracyclines, notably doxorubicin, are potent cytotoxic agents that substantially improved outcomes across numerous malignancies. However, their use is restricted by their cardiotoxicity, a dose-dependent adverse effect that manifests acutely, during treatment, or years post-therapy. It encompasses a spectrum of phenotypes including asymptomatic ventricular dysfunction, heart failure, arrhythmias, and cardiomyopathy, contributing to considerable morbidity and mortality as cancer survival rates improve. Objective: This narrative review summarises current insights into anthracycline-induced cardiotoxicity pathophysiology and evaluates pharmacologic strategies for its prevention and management. Methods: A comprehensive literature search was conducted through August 2025, prioritizing randomised controlled trials, meta-analyses, observational studies, and guideline statements addressing pharmacologic interventions to mitigate anthracycline cardiotoxicity. Results: Anthracycline cardiotoxicity arises from various mechanisms, including oxidative stress, mitochondrial dysfunction, topoisomerase IIβ-induced DNA damage, calcium dysregulation, and reticulum stress. Neurohormonal modulation with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers has shown modest preservation of left ventricular ejection fraction, especially when initiated early in high-risk patients; spironolactone appears more effective than eplerenone among mineralocorticoid receptor antagonists. Sacubitril/valsartan demonstrates promising superiority in preclinical and early clinical cohorts, though further randomised control trials are ongoing. Metabolic modulators such as metformin and sodium-glucose cotransporter 2 inhibitors exhibit cardio-protectivity via AMPK activation, attenuation of oxidative and inflammatory pathways, but evidence in non-diabetic cancer populations is limited. Statins have shown reduced left ventricular ejection fraction decline and lower cardiotoxicity rates in randomised studies, while dexrazoxane-through iron chelation and topoisomerase IIβ inhibition-remains the only approved agent for anthracycline-induced cardiotoxicity prevention, strongly supported by adult and paediatric data. Conclusion: Several pharmacologic strategies offer potential benefit in limiting anthracycline-induced cardiotoxicity and preserving cardiac function. Tailored, risk-based approaches that incorporate cardioprotective therapies early in anthracycline treatment-guided by biomarkers and imaging-are most promising. Further large-scale randomised studies are required to establish optimal combinations and confirm long-term benefit.