Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients
Abstract
:1. Introduction
2. Epidemiology of Anthracycline-Induced Cardiotoxicity
2.1. Incidence and Prevalence in Adult and Pediatric Populations
2.2. Anthracycline Use Across Different Malignancies
2.3. Cumulative Dose and Cardiotoxicity Thresholds
2.4. Identification of High-Risk Populations
2.5. Long-Term Outcomes and Healthcare Burden
3. Mechanisms of Anthracycline-Induced Cardiotoxicity
3.1. Oxidative Stress and Mitochondrial Dysfunction
3.2. Disruption of Calcium Homeostasis
3.3. Activation of Cell Death Pathways
3.4. DNA Damage and Epigenetic Modifications
3.5. Synergistic Effects with Other Cancer Therapies
4. Lifestyle Interventions for Prevention
5. Pharmacological Strategies for Prevention
6. Novel Therapeutic Pharmacological Interventions
6.1. SGLT2 Inhibitors
6.2. GLP-1 Receptor Agonists
6.3. Vericiguat
6.4. Sacubitril/Valsartan
7. Role of Multidisciplinary Cardio-Oncology Teams: Integrating Prevention and Management
8. Personalized Strategies Using Risk Stratification Tools
9. Long-Term Follow-Up Protocols
9.1. Biomarkers, Imaging, and Lifestyle Reassessment in Survivors
9.2. Integration of Cardio-Protective Strategies into Clinical Workflows
10. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Study Design | No. of Participants | Cancer Type (%) | Intervention | Follow-Up | Outcome |
---|---|---|---|---|---|---|
ACE-i/ARBs | ||||||
Nakame et al. (2005) [86] | Randomized, placebo-controlled | 40 | Lymphoma | Valsartan 80 mg daily | 0.25 months | ventricular remodeling and arrhythmia incidence LVEF unchanged in the treatment arm |
Cardinale et al. (2006) [87] | Randomized, placebo-controlled | 114 | AML, lymphoma, MM, breast | Enalapril from dose of 2.5 mg to 20 mg daily | 12 months | LVEF and EDV and ESV only in untreated patients |
Beta-Blockers | ||||||
Kaya et al. (2013) [88] | Double-blind, placebo-controlled | 45 | Breast | Nebivolol 5 mg daily | 6 months | Unchanged LVESD and LVEDD in the nebivolol group declines in LVEF in the intervention arm |
CECCY trial Avila et al. (2018) [89] | Double-blind, placebo-controlled | 200 | Breast | Carvedilol with incremental dose | 6 months | No impact of carvedilol in LVEF reduction |
Beta-Blockers + ACE-i/ARBs | ||||||
OVERCOME trial Bosch X et al. (2013) [90] | Double-blind, placebo-controlled | 90 | ALL, AML, lymphoma, MM | Enalapril + carvedilol | 6 months | LVEF unchanged in the intervention group while significantly in controls |
PRADA trial Heck et al. (2021) [91] | 2 × 2 factorial, randomized-placebo controlled trial | 120 | Breast | Metoprolol combined candesartan | 23 months | Candesartan + metoprolol > no change in LVEF, GLS, or LVESD candesartan alone > declines in GLS and EDV [91,92] |
MRAs | ||||||
ELEVATE trial Davis et al. (2019) [93] | Randomized placebo-controlled trial | 44 | Breast | Eplerenone 50 mg daily | 6 months | No significant differences in LV systolic or diastolic dysfunction were observed compared to the placebo group |
Statins | ||||||
PREVENT trial Hundley et al. (2022) [94] | Double-blind, placebo-controlled | 279 | Breast (85%), lymphoma (15%) | Atorvastatin 40 mg daily | 24 months | No difference in final LVEF, adjusted for baseline |
SPARE-HF trial Thavendiranathan et al. (2023) [95] | Double-blind, placebo-controlled | 112 | Breast (65%), lymphoma (21%), sarcoma (6%), thymoma (5%), leukemia (3%) | Atorvastatin 40 mg daily | 2.5 months | No difference in final LVEF, adjusted for baseline |
STOP-CA trial Neilan et al. (2023) [96] | Double-blind, placebo-controlled | 300 | Lymphoma (100%) | Atorvastatin 40 mg daily | 12 months | incidence of CTRCD in the statin arm |
Patient-Specific Factors | |
---|---|
Pre-existing cardiovascular conditions | Hypertension, diabetes, hyperlipidemia, coronary artery disease, or previous heart failure. |
Age | Older age increases susceptibility to cardiotoxicity due to general decline in cardiac function with aging. |
Genetic predisposition | Specific genetic factors can increase sensitivity to chemotherapy-induced heart damage. |
Gender | Gender-related differences may exist, with studies showing women may be at higher risk. |
Lifestyle factors | Smoking, sedentary lifestyle, and poor dietary habits can increase cardiovascular risk. |
Treatment-Specific Factors | |
Type and cumulative dose of chemotherapy agents | Anthracyclines (like doxorubicin) and trastuzumab are cardiotoxic, especially at higher cumulative doses. |
Radiotherapy | Chest irradiation increases the risk, particularly for left-sided breast cancer treatments. |
Combination therapies | Some chemotherapy regimens, when used with other medications that affect cardiac function, may increase the risk. |
Baseline Cardiac Function | |
Left ventricular ejection fraction (LVEF) | Lower baseline LVEF can indicate higher risk of developing significant cardiotoxicity. |
Cancer-Specific Factors | |
Type of cancer | Certain cancers (e.g., breast cancer or hematologic malignancies) carry different risks for chemotherapy-induced cardiac damage. |
Stage of cancer | The stage of cancer and its treatment protocol impact the risk of cardiotoxicity. |
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Spadafora, L.; Di Muro, F.M.; Intonti, C.; Massa, L.; Monelli, M.; Pedretti, R.F.E.; Palazzo Adriano, E.; Guarini, P.; Cantiello, G.; Bernardi, M.; et al. Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients. J. Cardiovasc. Dev. Dis. 2025, 12, 212. https://doi.org/10.3390/jcdd12060212
Spadafora L, Di Muro FM, Intonti C, Massa L, Monelli M, Pedretti RFE, Palazzo Adriano E, Guarini P, Cantiello G, Bernardi M, et al. Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients. Journal of Cardiovascular Development and Disease. 2025; 12(6):212. https://doi.org/10.3390/jcdd12060212
Chicago/Turabian StyleSpadafora, Luigi, Francesca Maria Di Muro, Chiara Intonti, Ludovica Massa, Mauro Monelli, Roberto Franco Enrico Pedretti, Edvige Palazzo Adriano, Pasquale Guarini, Gaia Cantiello, Marco Bernardi, and et al. 2025. "Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients" Journal of Cardiovascular Development and Disease 12, no. 6: 212. https://doi.org/10.3390/jcdd12060212
APA StyleSpadafora, L., Di Muro, F. M., Intonti, C., Massa, L., Monelli, M., Pedretti, R. F. E., Palazzo Adriano, E., Guarini, P., Cantiello, G., Bernardi, M., Russo, F., Cacciatore, S., Sabouret, P., Golino, M., Biondi Zoccai, G., Zimatore, F. R., & Dalla Vecchia, L. A. (2025). Lifestyle and Pharmacological Interventions to Prevent Anthracycline-Related Cardiotoxicity in Cancer Patients. Journal of Cardiovascular Development and Disease, 12(6), 212. https://doi.org/10.3390/jcdd12060212