Preventive Use of Beta-blockers for Anthracycline-induced Cardiotoxicity: A Network Meta-analysis

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2022 Aug 29

PMID 36035937

Authors

Dongsheng He

Jun Hu

Ying Li

Xiaofei Zeng

Affiliations

Soon will be listed here.

Abstract

Background: Anthracyclines are commonly used chemotherapeutic agents to treat malignant tumors. However, cardiotoxicity is a potentially serious adverse effect of anthracyclines. Beta-blockers may be effective in preventing anthracycline-induced cardiotoxicity (AIC). However, the lack of direct comparisons of various beta-blockers interferes with clinical decision-making. Network meta-analysis (NMA) was performed to assess the effectiveness of beta-blockers for AIC.

Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials. The last update was in May 2022. Randomized controlled trials (RCT) of beta-blockers for AIC were included. Four beta-blockers were selected for comparison based on the number of studies. NMA was conducted with STATA 14.0 software.

Results: A total of 10 RCTs (875 patients) met the selection criteria. NMA results showed that carvedilol was superior to bisoprolol [ = -0.50, 95% (-0.91, -0.10)] and nebivolol [ = -1.46, 95% (-2.82, -0.11)] in a delay of LVEF. The results of the cumulative probability ordering are as follows: carvedilol (83.8%) > metoprolol (71.8%) > bisoprolol (43.9%) > placebo (40.9%) > nebivolol (9.5%).

Conclusion: Based on the available evidence, carvedilol is the best beta-blocker for AIC, followed by metoprolol. However, additional studies with large samples should be conducted to confirm our findings.

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References

Anjos M, Fontes-Oliveira M, Costa V, Santos M, Ferreira R . An update of the molecular mechanisms underlying doxorubicin plus trastuzumab induced cardiotoxicity. Life Sci. 2021; 280:119760. DOI: 10.1016/j.lfs.2021.119760. View

Rocca C, Pasqua T, Cerra M, Angelone T . Cardiac Damage in Anthracyclines Therapy: Focus on Oxidative Stress and Inflammation. Antioxid Redox Signal. 2020; 32(15):1081-1097. DOI: 10.1089/ars.2020.8016. View

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. 2014; 9(2):95-8. DOI: 10.15420/ahhj.2011.9.2.95. View

Livi L, Barletta G, Martella F, Saieva C, Desideri I, Bacci C . Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial. JAMA Oncol. 2021; 7(10):1544-1549. PMC: 8391772. DOI: 10.1001/jamaoncol.2021.3395. View

Liesse K, Harris J, Chan M, Schmidt M, Chiu B . Dexrazoxane Significantly Reduces Anthracycline-induced Cardiotoxicity in Pediatric Solid Tumor Patients: A Systematic Review. J Pediatr Hematol Oncol. 2018; 40(6):417-425. PMC: 6059999. DOI: 10.1097/MPH.0000000000001118. View

Fabiani I, Aimo A, Grigoratos C, Castiglione V, Gentile F, Saccaro L . Oxidative stress and inflammation: determinants of anthracycline cardiotoxicity and possible therapeutic targets. Heart Fail Rev. 2020; 26(4):881-890. PMC: 8149360. DOI: 10.1007/s10741-020-10063-9. View

Henriksen P . Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart. 2017; 104(12):971-977. DOI: 10.1136/heartjnl-2017-312103. View

Kim S, Park Y, Lim J, Kim H . Effect of Docosahexaenoic Acid on Ca Signaling Pathways in Cerulein-Treated Pancreatic Acinar Cells, Determined by RNA-Sequencing Analysis. Nutrients. 2019; 11(7). PMC: 6682875. DOI: 10.3390/nu11071445. View

Wihandono A, Azhar Y, Abdurahman M, Hidayat S . The Role of Lisinopril and Bisoprolol to Prevent Anthracycline Induced Cardiotoxicity in Locally Advanced Breast Cancer Patients. Asian Pac J Cancer Prev. 2021; 22(9):2847-2853. PMC: 8850900. DOI: 10.31557/APJCP.2021.22.9.2847. View

10.

Bugiardini R, Yoon J, Kedev S, Stankovic G, Vasiljevic Z, Milicic D . Prior Beta-Blocker Therapy for Hypertension and Sex-Based Differences in Heart Failure Among Patients With Incident Coronary Heart Disease. Hypertension. 2020; 76(3):819-826. DOI: 10.1161/HYPERTENSIONAHA.120.15323. View

11.

Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni C, Veglia F . Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015; 131(22):1981-8. DOI: 10.1161/CIRCULATIONAHA.114.013777. View

12.

Abuosa A, Elshiekh A, Qureshi K, Abrar M, Kholeif M, Kinsara A . Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin. Indian Heart J. 2019; 70 Suppl 3:S96-S100. PMC: 6310701. DOI: 10.1016/j.ihj.2018.06.011. View

13.

Palaskas N, Lopez-Mattei J, Durand J, Iliescu C, Deswal A . Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment. J Am Heart Assoc. 2020; 9(2):e013757. PMC: 7033840. DOI: 10.1161/JAHA.119.013757. View

14.

Xu L, Long Y, Tang X, Zhang N . Cardioprotective Effects and Duration of Beta Blocker Therapy in Anthracycline-Treated Patients: A Systematic Review and Meta-analysis. Cardiovasc Toxicol. 2019; 20(1):11-19. DOI: 10.1007/s12012-019-09558-1. View

15.

Al-Gobari M, Al-Aqeel S, Gueyffier F, Burnand B . Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews. BMJ Open. 2018; 8(7):e021108. PMC: 6067373. DOI: 10.1136/bmjopen-2017-021108. View

16.

Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T . 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. DOI: 10.1002/ajh.21840. View

17.

Huang S, Zhao Q, Yang Z, Diao K, He Y, Shi K . Protective role of beta-blockers in chemotherapy-induced cardiotoxicity-a systematic review and meta-analysis of carvedilol. Heart Fail Rev. 2018; 24(3):325-333. PMC: 6476829. DOI: 10.1007/s10741-018-9755-3. View

18.

Fang Y, Nicol L, Harouki N, Monteil C, Wecker D, Debunne M . Improvement of left ventricular diastolic function induced by β-blockade: a comparison between nebivolol and metoprolol. J Mol Cell Cardiol. 2011; 51(2):168-76. DOI: 10.1016/j.yjmcc.2011.05.012. View

19.

Yun S, Vincelette N, Abraham I . Cardioprotective role of β-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J. 2015; 91(1081):627-33. DOI: 10.1136/postgradmedj-2015-133535. View

20.

Feher A, Baldassarre L, Sinusas A . Novel Cardiac Computed Tomography Methods for the Assessment of Anthracycline Induced Cardiotoxicity. Front Cardiovasc Med. 2022; 9:875150. PMC: 9094702. DOI: 10.3389/fcvm.2022.875150. View