Skip to main content

Advertisement

SpringerLink
Log in

Prevention of anthracycline-induced cardiotoxicity: a systematic review and network meta-analysis

  • Review Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Anthracycline based chemotherapy is commonly used in many malignancies. While life expectancy increases with the use of this medication, cardiac toxicity causes a risk for patients’ health due to anthracyclines. Objective This systematic review and meta-analysis emphasizes on prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Methods We conducted a systematic review of electronic databases including PubMed, Medline, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Library from inception to June 2019 collecting published articles on primary prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. We conducted a network meta-analysis and a pairwise meta-analysis in order to compare direct and indirect cardiac agents group with control group calculate left ventricular ejection fraction change. Primary studies results were pooled using random effects model, frequent network meta-analyses, and performed pairwise meta-analysis using netmeta and meta packages respectively in R software version 3.5.1. Results Twelve studies reported left ventricular ejection fraction outcome among 526 patients in the cardiac agent group and 508 in the control group. Based on Surface Under the Cumulative Ranking cure result, spironolactone was the best in left ventricular ejection fraction change and based on meta-analysis, cardiac group had 1.98 unit left ventricular ejection fraction more than the control group (MD = 1.98, 95% CI 0.15–3.81, p value = 0.03). Conclusions The amount of left ventricular ejection fraction used by cardiac agents in anthracycline-based chemotherapy was reduced to a lesser extent. The effective and ineffective drugs were spironolactone and metoprolol, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Chotenimitkhun R, D’Agostino R Jr, Lawrence JA, Hamilton CA, Jordan JH, Vasu S, et al. Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function. Can J Cardiol. 2015;31(3):302–7.

    Article  Google Scholar 

  2. Jhorawat R, Kumari S, Varma SC, Rohit MK, Narula N, Suri V, et al. Preventive role of carvedilol in adriamycin-induced cardiomyopathy. Indian J Med Res. 2016;144(5):725–9.

    Article  CAS  Google Scholar 

  3. Marty M, Espie M, Llombart A, Monnier A, Rapoport BL, Stahalova V. Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Ann Oncol. 2006;17(4):614–22.

    Article  CAS  Google Scholar 

  4. Elitok A, Oz F, Cizgici AY, Kilic L, Ciftci R, Sen F, et al. Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: a prospective randomized controlled study with six-month follow-up. Cardiol J. 2014;21(5):509–15.

    Article  Google Scholar 

  5. Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671–80.

    Article  CAS  Google Scholar 

  6. Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013;167(5):2306–10.

    Article  Google Scholar 

  7. Christiansen S. Recovery from anthracycline cardiomyopathy–how can it be explained? J Heart Lung Transpl. 2009;28(7):751.

    Article  Google Scholar 

  8. Kurihara C, Nishimura T, Nawata K, Kinoshita O, Hisagi M, Motomura N, et al. Successful bridge to recovery with VAD implantation for anthracycline-induced cardiomyopathy. J Artif Organs. 2011;14(3):249–52.

    Article  Google Scholar 

  9. Kheiri B, Abdalla A, Osman M, Haykal T, Chahine A, Ahmed S, et al. Meta-analysis of carvedilol for the prevention of anthracycline-induced cardiotoxicity. Am J Cardiol. 2018;122(11):1959–64.

    Article  CAS  Google Scholar 

  10. Akpek M, Ozdogru I, Sahin O, Inanc M, Dogan A, Yazici C, et al. Protective effects of spironolactone against anthracycline-induced cardiomyopathy. Eur J Heart Fail. 2015;17(1):81–9.

    Article  CAS  Google Scholar 

  11. Nabati M, Janbabai G, Esmailian J, Yazdani J. Effect of rosuvastatin in preventing chemotherapy-induced cardiotoxicity in women with breast cancer: a randomized, single-blind, placebo-controlled trial. J Cardiovasc Pharmacol Ther. 2019;24(3):233–41.

    Article  CAS  Google Scholar 

  12. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014;64(9):938–45.

    Article  CAS  Google Scholar 

  13. Page MJ, Moher D. Evaluations of the uptake and impact of the Preferred Reporting Items for systematic reviews and meta-analyses (PRISMA) Statement and extensions: a scoping review. Syst Rev. 2017;6(1):263.

    Article  Google Scholar 

  14. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  Google Scholar 

  15. Brignardello-Petersen R, Bonner A, Alexander PE, Siemieniuk RA, Furukawa TA, Rochwerg B, et al. Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis. J Clin Epidemiol. 2018;93:36–44.

    Article  Google Scholar 

  16. Schünemann HJ, Oxman AD, Brozek J, Glasziou P, Bossuyt P, Chang S, et al. GRADE: assessing the quality of evidence for diagnostic recommendations. BMJ Evid Based Med. 2008;13(6):162–3.

    Article  Google Scholar 

  17. Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010;85(11):894–6.

    Article  CAS  Google Scholar 

  18. Salehi R, Zamani B, Esfehani A, Ghafari S, Abasnezhad M, Goldust M. Protective effect of carvedilol in cardiomyopathy caused by anthracyclines in patients suffering from breast cancer and lymphoma. Am Heart Hosp J. 2011;9(2):95–8.

    Article  Google Scholar 

  19. Beheshti AT, Toroghi HM, Hosseini G, Zarifian A, Shandiz FH, Fazlinezhad A. Carvedilol administration can prevent doxorubicin-induced cardiotoxicity: a double-blind randomized trial. Cardiology. 2016;134(1):47–53.

    Article  Google Scholar 

  20. Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, das Dores Cruz F, Brandão SMG, Rigaud VOC, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol. 2018;71(20):2281–90.

    Article  CAS  Google Scholar 

  21. Cochera F, Dinca D, Bordejevic DA, Citu IM, Mavrea AM, Andor M, et al. Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer. Cancer Manag Res. 2018;10:2071–81.

    Article  CAS  Google Scholar 

  22. Jo SH, Kim LS, Kim SA, Kim HS, Han SJ, Park WJ, et al. Evaluation of short-term use of N-acetylcysteine as a strategy for prevention of anthracycline-induced cardiomyopathy: EPOCH trial—a prospective randomized study. Korean Circ J. 2013;43(3):174–81.

    Article  CAS  Google Scholar 

  23. Liu L, Liu Z, Liu Y, Zheng Z, Liang X, Han Y, et al. Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer. Zhonghua zhong liu za zhi [Chin J Oncol]. 2013;35(12):936–40.

    CAS  Google Scholar 

  24. Cai F, Luis MAF, Lin X, Wang M, Cai L, Cen C, et al. Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: preventive strategies and treatment. Mol Clin Oncol. 2019;11(1):15–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.

    Article  Google Scholar 

  26. Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med. 1977;62(2):200–8.

    Article  Google Scholar 

  27. Tajiri K, Aonuma K, Sekine I. Cardio-oncology: a multidisciplinary approach for detection, prevention and management of cardiac dysfunction in cancer patients. Jpn J Clin Oncol. 2017;47(8):678–82.

    Article  Google Scholar 

  28. Tonkon M, Awan N, Niazi I, Hanley P, Baruch L, Wolf R, et al. A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group. Int J Clin Pract. 2000;54(1):11–4.

    CAS  PubMed  Google Scholar 

  29. Vizzardi E, D’Aloia A, Giubbini R, Bordonali T, Bugatti S, Pezzali N, et al. Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure. Am J Cardiol. 2010;106(9):1292–6.

    Article  CAS  Google Scholar 

  30. Korzeniowska K, Jankowski J, Cieślewicz A, Jabłecka A. Is it possible to prevent chemotherapy-induced heart failure with cardiovascular drugs—the review of the current clinical evidence. Ther Clin Risk Manag. 2019;15:1095–110.

    Article  CAS  Google Scholar 

  31. Zhang L, Zhang S, Jiang H, Sun A, Zou Y, Ge J. Effects of statin treatment on cardiac function in patients with chronic heart failure: a meta-analysis of randomized controlled trials. Clin Cardiol. 2011;34(2):117–23.

    Article  Google Scholar 

  32. Zhang Y, Liu J, Li Y, Tan N, Du K, Zhao H, et al. Protective role of enalapril in anthracycline-induced cardiotoxicity: a systematic review. Front Pharmacol. 2020;11:788.

    Article  CAS  Google Scholar 

  33. Huang S, Zhao Q, Yang ZG, Diao KY, He Y, Shi K, et al. Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol. Heart Fail Rev. 2019;24(3):325–33.

    Article  CAS  Google Scholar 

  34. Zhan T, Daniyal M, Li J, Mao Y. Preventive use of carvedilol for anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials. Herz. 2019.

  35. Abdel-Qadir H, Ong G, Fazelzad R, Amir E, Lee D, Thavendiranathan P, et al. Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis. Ann Oncol. 2016;28(3):628–33.

    Article  Google Scholar 

  36. Wiernik PH, Hu X, Ratech H, Fineberg S, Marino P, Schleider MA, et al. Non-Hodgkin’s lymphoma in women with breast cancer. Cancer J. 2000;6(5):336–42.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Bahareh Malmir, Ph.D in Applied Linguistics, who performed the language edition of the present article.

Funding

The authors received no specific funding for this work.

Author information

Authors and Affiliations

  1. Cardio-Oncology Department and Research Center, Rajaie Cardiovascular Medical and Research Center, Tehran, Iran

    Azin Alizadehasl

  2. Health Technology Assessment, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran

    Nashmil Ghadimi & Sara Kaveh

  3. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

    Majid Maleki & Feridoun Noohi

  4. Hematology-Oncology and Stem Cell Transplantation Research Center, School of Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ardeshir Ghavamzadeh

  5. Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hossein Hosseinifard

Authors
  1. Azin Alizadehasl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nashmil Ghadimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Kaveh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Majid Maleki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ardeshir Ghavamzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feridoun Noohi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hossein Hosseinifard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hossein Hosseinifard.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1178 kb)

Supplementary material 2 (DOCX 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alizadehasl, A., Ghadimi, N., Kaveh, S. et al. Prevention of anthracycline-induced cardiotoxicity: a systematic review and network meta-analysis. Int J Clin Pharm 43, 25–34 (2021). https://doi.org/10.1007/s11096-020-01146-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-020-01146-6

Keywords

Search

Navigation