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Abstract

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 βeta-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 data are awaited. 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.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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