Cardiovascular Toxicology

, Volume 17, Issue 2, pp 130–139 | Cite as

Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy

  • Ghasem Janbabai
  • Maryam Nabati
  • Mohsen Faghihinia
  • Soheil Azizi
  • Samaneh Borhani
  • Jamshid Yazdani


Anthracycline (ANT) is a topoisomerase-interacting agent that is used in most malignancy treatments. We investigated the efficacy of enalapril (angiotensin-converting enzyme inhibitor) in the prevention of ANT-induced cardiomyopathy. In this randomized, single-blind, and placebo-controlled study, 69 patients with a newly diagnosed malignancy for which ANT therapy was planned were randomly assigned to either a group receiving enalapril (n = 34) or placebo (n = 35). Echocardiography studies were performed before chemotherapy and at 6 months after randomization. Additionally, troponin I and creatinine kinase-MB (CK-MB) were measured 1 month after the initiation of chemotherapy. In the enalapril group, the mean left ventricular ejection fraction (LVEF) (p = 0.58) was the same at baseline and 6 months after randomization. Conversely, LVEF significantly decreased in the control group (p < 0.001). Additionally, LV end systolic volume and left atrial diameter were significantly increased compared with the baseline measures in the control group. According to the tissue Doppler study, the mitral annuli early diastolic (e′) and peak systolic (s′) velocities were significantly reduced, and the E (the peak early diastolic velocity)/e′ ratio was significantly increased in the control group. Furthermore, the TnI and CK-MB levels were significantly higher in the control group than in the enalapril group. Enalapril appears efficacious in preserving systolic and diastolic function in cancer patients treated with ANTs.


Anticancer drug Anthracyclines Cardiotoxicity Cardio protection 



This study was Dr. Mohsen Faghihinia’s postgraduate thesis. The authors would like to thank all the patients who enrolled in this study and the staff at the Toba Oncology Department, Sari, Iran. Financial support was obtained from the Research Council of the Mazandaran University of Medical Sciences to Dr. Maryam Nabati, Assistant Professor, Fellowship of Echocardiography.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    DeVita, V. T., Lawrence, T. S., Rosenberg, S. A., DePinho, R. A., & Weinberg, R. A. (Eds.). (2011). DeVita, Hellman, and Rosenberg’s Cancer: Principles and practice of oncology (9th ed., pp. 404–407). Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
  2. 2.
    Vejpongsa, P., & Yeh, E. T. (2014). Prevention of anthracycline-induced cardiotoxicity: Challenges and opportunities. Journal of the American College of Cardiology, 64(9), 938–945.CrossRefPubMedGoogle Scholar
  3. 3.
    Cardinale, D., Colombo, A., Lamantia, G., Colombo, N., Civelli, M., De Giacomi, G., et al. (2010). Anthracycline-induced cardiomyopathy clinical relevance and response to pharmacologic therapy. Journal of the American College of Cardiology, 55(3), 213–220.CrossRefPubMedGoogle Scholar
  4. 4.
    Sawyer, D. B., Peng, X., Chen, B., Pentassuglia, L., & Lim, C. C. (2010). Mechanisms of anthracycline cardiac injury: Can we identify strategies for cardioprotection? Progress in Cardiovascular Diseases, 53(2), 105–113.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., et al. (2009). 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 53, 1343–1382.CrossRefGoogle Scholar
  6. 6.
    Sacco, G., Bigioni, M., & Evangelista, S. (2001). Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. European Journal of Pharmacology, 414, 71–78.CrossRefPubMedGoogle Scholar
  7. 7.
    Vaynblat, M., Shah, H. R., Bhaskaran, D., Ramdev, G., Davis, W. J, 3rd, Cunningham, J. N, Jr, & Chiavarelli, M. (2002). Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin. European Journal of Heart Failure, 4, 583–586.CrossRefPubMedGoogle Scholar
  8. 8.
    Cardinale, D., Colombo, A., Sandri, M. T., Lamantia, G., Colombo, N., Civelli, M., et al. (2006). Prevention of high-risk chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation, 114, 2474–2481.CrossRefPubMedGoogle Scholar
  9. 9.
    Bosch, X., Rovira, M., Sitges, M., Domènech, A., Ortiz-Pérez, J. T., de Caralt, T. M., et al. (2013). Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathiesthe OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). Journal of the American College of Cardiology, 61(23), 2355–2362.CrossRefPubMedGoogle Scholar
  10. 10.
    Pfeffer, B., Tziros, C., & Katz, R. J. (2009). Current concepts of anthracycline cardiotoxicity: Pathogenesis, diagnosis and prevention. British Journal of Cardiology, 16(2), 85–89.Google Scholar
  11. 11.
    Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L, Jr, et al. (2003). Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 42, 1206–1252.CrossRefPubMedGoogle Scholar
  12. 12.
    American Diabetes Association. (2010). Diagnosis and classification of diabetes mellitus. Diabetes Care, 33(Suppl 1), S62–S69.CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Arnett, D. K., Jacobs, D. R., Luepker, R. V., Blackburn, H., Armstrong, C., & Claas, S. A. (2005). Twenty-year trends in serum cholesterol, hypercholesterolemia, and cholesterol medication use The Minnesota Heart Survey, 1980–1982 to 2000–2002. Circulation, 112(25), 3884–3891.CrossRefPubMedGoogle Scholar
  14. 14.
    Silber, J. H., Cnaan, A., Clark, B. J., Paridon, S. M., Chin, A. J., Rychik, J., et al. (2004). Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. Journal of Clinical Oncology, 22, 820–828.CrossRefPubMedGoogle Scholar
  15. 15.
    Barrett-Lee, P., Dixon, J., Farrell, C., Jones, A., Leonard, R., Murray, N., et al. (2009). Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Annals of Oncology, mdn728.Google Scholar
  16. 16.
    Perez, E. A., Suman, V. J., Davidson, N. E., Kaufman, P. A., Martino, S., Dakhil, S. R., et al. (2004). Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. Journal of Clinical Oncology, 22, 3700–3704.CrossRefPubMedGoogle Scholar
  17. 17.
    Nagueh, S. F., Appleton, C. P., Gillebert, T. C., Marino, P. N., Oh, J. K., Smiseth, O. A., et al. (2009). Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Journal of the American Society of Echocardiography, 22(2), 107–133.CrossRefPubMedGoogle Scholar
  18. 18.
    Plana, J. C., Galderisi, M., Barac, A., Ewer, M. S., Ky, B., Scherrer-Crosbie, M., et al. (2014). Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 27(9), 911–939.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ghasem Janbabai
    • 2
  • Maryam Nabati
    • 1
  • Mohsen Faghihinia
    • 3
  • Soheil Azizi
    • 4
  • Samaneh Borhani
    • 5
  • Jamshid Yazdani
    • 6
  1. 1.Department of Cardiology, Faculty of Medicine, Fatemeh Zahra Teaching HospitalMazandaran University of Medical SciencesSariIran
  2. 2.Department of Hematology, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  3. 3.Student Research Committee, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  4. 4.Department of Pathology, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  5. 5.Mazandaran University of Medical SciencesSariIran
  6. 6.Department of Biostatics, Faculty of HealthMazandaran University of Medical SciencesSariIran

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