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Reviews on Recent Clinical Trials

Author(s): Ehsan Keshavarzian, Tella Sadighpour, Seyed Mohammadreza Mortazavizadeh, Mohammadhossein Soltani, Amir Farzin Motevalipoor, Shahriyar Shahbazi Khamas, Mohammad Moazen, Mohammad Kogani, Seyed Mohammad Amin Hashemipour*, Hamid Hosseinpour and Rohollah Valizadeh*

DOI: 10.2174/1574887118666230118102252

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Prophylactic Agents for Preventing Cardiotoxicity Induced Following Anticancer Agents: A Systematic Review and Meta-Analysis of Clinical Trials

Page: [112 - 122] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated with cardiomyopathy. This meta-analysis aimed to compare the effects of prophylactic agents for preventing cardiotoxicity induced following anticancer agents.

Methods: In this meta-analysis, Scopus, Web of Science, and PubMed were surfed for articles published by December 30th, 2020. The keywords were angiotensin‐converting enzyme inhibitor (ACEI), enalapril, captopril, angiotensin receptor blocker, beta blocker, metoprolol, bisoprolol, isoprolol, statin, valsartan, losartan, eplerenone, idarubicin, nebivolol, dihydromyricetin, ampelopsin, spironolactone, dexrazoxane, antioxidants, cardiotoxicity, n-acetyl-tryptamine, cancer, neoplasms, chemotherapy, anthracyclines, doxorubicin, daunorubicin, epirubicin, idarubicin, ejection fraction or a combination of them in the titles or abstracts.

Results: A total of 17 articles out of 728 studies examining 2,674 patients were included in this systematic review and meta-analysis. Ejection fraction (EF) values in the baseline, 6-month, and 12-month follow-up in the intervention group turned out to be 62.52 ± 2.48, 59.63 ± 4.85, and 59.42 ± 4.53, whereas in the control group appeared to be 62.81 ± 2.58, 57.69 ± 4.32, and 58.60 ± 4.58, respectively. Through comparison of the two groups, EF was found to increase in the intervention group by 0.40 after 6 months (Standardized mean difference (SMD): 0.40, 95% confidence interval (CI): 0.27, 0.54), thus proving higher than that of the control groups following the cardiac drugs.

Conclusion: This meta-analysis showed that prophylactic treatment with cardio-protective drugs, including dexrazoxane, beta blocker, and ACEI drugs in patients undergoing chemotherapy with anthracycline, have a protective effect on LVEF and prevent EF drop.

[1]
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[2]
Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R. EUROCARE-4. survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer 2009; 45(6): 931-91.
[http://dx.doi.org/10.1016/j.ejca.2008.11.018] [PMID: 19171476]
[3]
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56(2): 185-229.
[http://dx.doi.org/10.1124/pr.56.2.6] [PMID: 15169927]
[4]
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer 2003; 97(11): 2869-79.
[http://dx.doi.org/10.1002/cncr.11407] [PMID: 12767102]
[5]
Henriksen PA. Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention. Heart 2018; 104(12): 971-7.
[http://dx.doi.org/10.1136/heartjnl-2017-312103] [PMID: 29217634]
[6]
Russell RR, Alexander J, Jain D, et al. The role and clinical effectiveness of multimodality imaging in the management of cardiac complications of cancer and cancer therapy. J Nucl Cardiol 2016; 23(4): 856-84.
[http://dx.doi.org/10.1007/s12350-016-0538-8] [PMID: 27251147]
[7]
Sharalaya Z, Collier P. Prevention of cardiotoxicities with traditional and novel chemotherapeutic agents. Curr Heart Fail Rep 2018; 15(4): 260-9.
[http://dx.doi.org/10.1007/s11897-018-0400-1] [PMID: 29938321]
[8]
Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of anthracyclines. Front Cardiovasc Med 2020; 7: 26.
[http://dx.doi.org/10.3389/fcvm.2020.00026] [PMID: 32258060]
[9]
Volkova M, Russell R III. Anthracycline cardiotoxicity: Prevalence, pathogenesis and treatment. Curr Cardiol Rev 2012; 7(4): 214-20.
[http://dx.doi.org/10.2174/157340311799960645] [PMID: 22758622]
[10]
Baech J, Hansen SM, Lund PE, et al. Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines. Br J Haematol 2018; 183(5): 717-26.
[http://dx.doi.org/10.1111/bjh.15603] [PMID: 30406945]
[11]
Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991; 266(12): 1672-7.
[http://dx.doi.org/10.1001/jama.1991.03470120074036] [PMID: 1886191]
[12]
Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA, Oliveira PJ. Doxorubicin-induced cardiotoxicity: From bioenergetic failure and cell death to cardiomyopathy. Med Res Rev 2014; 34(1): 106-35.
[http://dx.doi.org/10.1002/med.21280] [PMID: 23494977]
[13]
Varricchi G, Ameri P, Cadeddu C, et al. Antineoplastic drug-induced cardiotoxicity: A redox perspective. Front Physiol 2018; 9: 167.
[http://dx.doi.org/10.3389/fphys.2018.00167] [PMID: 29563880]
[14]
Toko H, Oka T, Zou Y, et al. Angiotensin II type 1a receptor mediates doxorubicin-induced cardiomyopathy. Hypertens Res 2002; 25(4): 597-603.
[http://dx.doi.org/10.1291/hypres.25.597] [PMID: 12358147]
[15]
Shankar SM, Marina N, Hudson MM, et al. Monitoring for cardiovascular disease in survivors of childhood cancer: report from the cardiovascular disease task force of the children’s oncology group. Pediatrics 2008; 121(2): e387-96.
[http://dx.doi.org/10.1542/peds.2007-0575] [PMID: 18187811]
[16]
Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91(5): 710-7.
[http://dx.doi.org/10.7326/0003-4819-91-5-710] [PMID: 496103]
[17]
Saini J, Rich MW, Lyss AP. Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases. Ann Intern Med 1987; 106(6): 814-6.
[http://dx.doi.org/10.7326/0003-4819-106-6-814] [PMID: 3579067]
[18]
Abuosa AM, Elshiekh AH, Qureshi K, et al. Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin. Indian Heart J 2018; 70(S3): S96-s100.
[http://dx.doi.org/10.1016/j.ihj.2018.06.011] [PMID: 30595329]
[19]
Calvillo-Argüelles O, Abdel-Qadir H, Michalowska M, et al. Cardioprotective effect of statins in patients with her2-positive breast cancer receiving trastuzumab therapy. Can J Cardiol 2019; 35(2): 153-9.
[http://dx.doi.org/10.1016/j.cjca.2018.11.028] [PMID: 30760421]
[20]
Bhagat A, Kleinerman ES. Anthracycline-induced cardiotoxicity: Causes, mechanisms, and prevention. Adv Exp Med Biol 2020; 1257: 181-92.
[http://dx.doi.org/10.1007/978-3-030-43032-0_15] [PMID: 32483740]
[21]
Kim IH, Lee JE, Youn HJ, Song BJ, Chae BJ. Cardioprotective effect of dexrazoxane in patients with her2-positive breast cancer who receive anthracycline based adjuvant chemotherapy followed by trastuzumab. J Breast Cancer 2017; 20(1): 82-90.
[http://dx.doi.org/10.4048/jbc.2017.20.1.82] [PMID: 28382098]
[22]
Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: A population-based study. J Clin Oncol 2011; 29(19): 2635-44.
[http://dx.doi.org/10.1200/JCO.2010.33.5422] [PMID: 21632503]
[23]
Fajardo G, Zhao M, Berry G, Wong LJ, Mochly-Rosen D, Bernstein D. β2-adrenergic receptors mediate cardioprotection through crosstalk with mitochondrial cell death pathways. J Mol Cell Cardiol 2011; 51(5): 781-9.
[http://dx.doi.org/10.1016/j.yjmcc.2011.06.019] [PMID: 21756913]
[24]
Gujral DM, Lloyd G, Bhattacharyya S. Effect of prophylactic betablocker or ACE inhibitor on cardiac dysfunction & heart failure during anthracycline chemotherapy ± trastuzumab. Breast 2018; 37: 64-71.
[http://dx.doi.org/10.1016/j.breast.2017.10.010] [PMID: 29101824]
[25]
Kheiri B, Abdalla A, Osman M, et al. Meta-analysis of carvedilol for the prevention of anthracycline-induced cardiotoxicity. Am J Cardiol 2018; 122(11): 1959-64.
[http://dx.doi.org/10.1016/j.amjcard.2018.08.039] [PMID: 30292333]
[26]
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6(7): e1000097.
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[27]
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17(1): 1-12.
[http://dx.doi.org/10.1016/0197-2456(95)00134-4] [PMID: 8721797]
[28]
Moher D, Schulz KF, Altman DG. The CONSORT statement: Tevised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001; 357(9263): 1191-4.
[http://dx.doi.org/10.1016/S0140-6736(00)04337-3] [PMID: 11323066]
[29]
Blaes AH, Gaillard P, Peterson BA, Yee D, Virnig B. Angiotensin converting enzyme inhibitors may be protective against cardiac complications following anthracycline chemotherapy. Breast Cancer Res Treat 2010; 122(2): 585-90.
[http://dx.doi.org/10.1007/s10549-009-0730-5] [PMID: 20058065]
[30]
Cochera F, Dinca D, Bordejevic DA, et al. Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer. Cancer Manag Res 2018; 10: 2071-81.
[http://dx.doi.org/10.2147/CMAR.S166481] [PMID: 30038521]
[31]
Elitok A, Oz F, Cizgici AY, 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.
[http://dx.doi.org/10.5603/CJ.a2013.0150] [PMID: 24142687]
[32]
Gupta V, Kumar Singh S, Agrawal V, Bali Singh T. Role of ACE inhibitors in anthracycline-induced cardiotoxicity: A randomized, double-blind, placebo-controlled trial. Pediatr Blood Cancer 2018; 65(11): e27308.
[http://dx.doi.org/10.1002/pbc.27308] [PMID: 30009543]
[33]
Janbabai G, Nabati M, Faghihinia M, Azizi S, Borhani S, Yazdani J. Effect of enalapril on preventing anthracycline-induced cardiomyopathy. Cardiovasc Toxicol 2017; 17(2): 130-9.
[http://dx.doi.org/10.1007/s12012-016-9365-z] [PMID: 27003392]
[34]
Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol 1997; 15(4): 1333-40.
[http://dx.doi.org/10.1200/JCO.1997.15.4.1333] [PMID: 9193324]
[35]
Tashakori Beheshti A, Mostafavi Toroghi H, Hosseini G, Zarifian A, Homaei Shandiz F, Fazlinezhad A. Carvedilol administration can prevent doxorubicin-induced cardiotoxicity: A double-blind randomized trial. Cardiology 2016; 134(1): 47-53.
[http://dx.doi.org/10.1159/000442722] [PMID: 26866364]
[36]
Armenian SH, Hudson MM, Chen MH, et al. Rationale and design of the Children’s Oncology Group (COG) study ALTE1621: A randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure. BMC Cardiovasc Disord 2016; 16(1): 187.
[http://dx.doi.org/10.1186/s12872-016-0364-6] [PMID: 27716152]
[37]
Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: An observational clinical cohort study. J Am Coll Cardiol 2012; 60(23): 2384-90.
[http://dx.doi.org/10.1016/j.jacc.2012.07.067] [PMID: 23141499]
[38]
Słowik A, Jagielski P, Potocki P, et al. Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in women with low-risk breast cancer: Results of a prospective randomized study. Kardiol Pol 2020; 78(2): 131-7.
[http://dx.doi.org/10.33963/KP.15163] [PMID: 31995035]
[39]
Cardinale D, Ciceri F, Latini R, et al. Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The international cardiooncology society-one trial. Eur J Cancer 2018; 94: 126-37.
[http://dx.doi.org/10.1016/j.ejca.2018.02.005] [PMID: 29567630]
[40]
Jo SH, Kim LS, Kim SA, 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.
[http://dx.doi.org/10.4070/kcj.2013.43.3.174] [PMID: 23613694]
[41]
Lopez M, Vici P, Di LK, et al. Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J Clin Oncol 1998; 16(1): 86-92.
[http://dx.doi.org/10.1200/JCO.1998.16.1.86] [PMID: 9440727]
[42]
Schiavetti A, Castello MA, Versacci P, et al. Use of ICRF-187 for prevention of anthracycline cardiotoxicity in children: Preliminary results. Pediatr Hematol Oncol 1997; 14(3): 213-22.
[http://dx.doi.org/10.3109/08880019709009491] [PMID: 9185206]
[43]
Abdali F, Taghavi S, Vazifekhah S, Naghavi BM, Mirza AAM. Effect of progesterone on latent phase prolongation in patients with preterm premature rupture of membranes. Acta Med Iran 2017; 55(12): 772-8.
[PMID: 29373884]
[44]
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 2020; 20(1): 11-9.
[http://dx.doi.org/10.1007/s12012-019-09558-1] [PMID: 31832905]
[45]
Santos D, Moreno AJ, Leino RL, Froberg MK, Wallace KB. Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol 2002; 185(3): 218-27.
[http://dx.doi.org/10.1006/taap.2002.9532] [PMID: 12498738]
[46]
Yun S, Vincelette ND, 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.
[http://dx.doi.org/10.1136/postgradmedj-2015-133535] [PMID: 26399268]
[47]
Chapman JAW, Meng D, Shepherd L, et al. Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer. J Natl Cancer Inst 2008; 100(4): 252-60.
[http://dx.doi.org/10.1093/jnci/djn014] [PMID: 18270335]
[48]
Ewer MS, Ali MK, Mackay B, et al. A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving adriamycin. J Clin Oncol 1984; 2(2): 112-7.
[http://dx.doi.org/10.1200/JCO.1984.2.2.112] [PMID: 6699662]
[49]
Lewinter C, Nielsen TH, Edfors LA, et al. A systematic review and meta-analysis of beta-blockers and renin–angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer. Eur Heart J 2022; 43(27): 2562-9.
[PMID: 34951629]