Abstract
Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Cancer is one major cause of morbidity and mortality worldwide, and in response, anticancer therapies are increasing to prolong the survival of patients [1]. In comparison, the cardiotoxicity associated with anticancer therapy poses a challenge for oncologists and cardiologists [2]. Of these, anthracyclines and trastuzumab are widely used to treat breast cancer, the leading cause of death from cancer in women, but are associated with several cardiovascular toxicities [3,4,5]. The latest oncology cardiology guidelines recommend angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), beta-blocker (BB), and calcium channel blocker (CCB) classes as cardioprotective drugs [6]. Although ACEIs, ARBs, and BBs have been investigated as primary prevention options, the strength of the available evidence does not support using these medications routinely for breast cancer patients receiving anthracyclines and/or trastuzumab [7, 8]. Currently, it is not clear which drug is the best choice as the primary option. Incorporating various recent studies into an updated meta-analysis can significantly improve the current body of evidence available. The purpose of this review is to thoroughly analyze studies that specifically focus on the heart-protective benefits of ACEI/ARBs and BBs in breast cancer patients who have undergone treatment with anthracycline or trastuzumab.
Methods
The PRISMA Checklist 2020 was used to perform this study (Supplemental Table 1) [9].
Search strategy
From their inception through May 11, 2022, we searched PubMed, EMBASE, Cochrane Library, and Web of Science without regard to language or abstract requirements. Two authors (YG and JJ) were the only ones for whom the search was allowed. In addition, we searched past systematic reviews for any references to RCTs that were not returned by our own search. Reviews, in vitro experiments, and animal research were not included. The intended studies were RCTs comparing the effects of anthracyclines, trastuzumab, and mono- or combination therapy with an ACEI, ARB, or BB on LVEF in comparison to placebo. The search terms were anthracycline*/Doxorubicin*/Adriamycin*/Daunorubicin*/Epirubicin*/Trastuzumab/beta blocker/ACEI/ARB et al. Supplemental Table 2 contains the PubMed search methodology.
Eligibility criteria of articles
We incorporated published RCTs comparing ACEI, ARB, BB, or both with placebo. RCTs involving breast cancer patient enrollment qualified as studies for inclusion. We counted each intervention separately for trials that included more than two comparisons. Studies were to include data on adverse events and LVEF in percent (%) before and after breast cancer treatment. A multi-gated acquisition (MUGA) scan, magnetic resonance imaging (MRI), or echocardiography might have been used to determine the LVEF. Studies that were not randomized, looked at different tumor kinds, or in which the BC group’s outcomes could not be examined separately were eliminated.
The titles and abstracts of the retrieved papers were examined independently by two reviewers (YG and RTW). The complete texts of trials that might be considered eligible were studied in order to make this determination. Discussion was used to settle any disputes, and a third reviewer (HL) was contacted if necessary.
Data extraction
Using standardized forms, two reviewers (YG and JJ) independently retrieved data from accepted papers. A third reviewer (HL) settled any differences. Publication data were among the information that was extracted (e.g., publication year, authors), participant data (e.g., number, female sex, age, primary study drug), intervention data (e.g., drug, duration, duration of ACEI/ARB or BB), and outcome data (e.g., mean baseline EF, mean final EF, type of LVEF measurement).
Risk of bias assessment
Using version 2 of Cochrane’s revised tool to assess the risk of bias in randomized trials (RoB 2), two reviewers (YG and JJ) independently evaluated the risk of bias [10] (see Supplementary Table 3). Any discrepancies were discussed with a third reviewer (RTW) before being decided. Based on the randomization method, variations from the intended intervention, missing outcome data, measurement of the outcome, and choice of the report result, we assessed the likelihood of bias.
Assessment of evidence quality
The quality of the evidence was evaluated using the GRADE (grading of recommendations assessment, development, and evaluation) assessment [11]. Each key outcome’s finding table was summarized and presented.
Statistics
The outcome data on the results are shown as mean difference (MD) with standard deviation (SD) or with associated 95% confidence intervals (95% CIs) of LVEF during the follow-up period. If MD ± SD was not presented, it was computed using the VassarStats calculator based on the median, range, and number of cases. Considering differences in the staging of breast cancer, treatment duration, and demographic characteristics in different studies, we performed meta-analyses of RCT data with a random effects model. Statistical analysis was performed using Stata 15 and R software 4.2.1. We used a frequentist meta-analysis to produce forest plots and estimate the I2 statistic along with a 95% confidence interval, which indicates the percentage of the variability that is not due to random errors. This approach will provide a heterogeneity assessment.
Results
Search results
A total of 249 studies were found in our preliminary search in PubMed, Embase, Cochrane Library, and Web of Science. After removing duplicates, 223 studies were assessed for eligibility. Additionally, one study was included from the references, through which we reviewed previous systematic reviews. Fifteen random clinical studies [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26] with a total of 1977 patients were included in the analysis. Figure 1 depicts the PRISMA search strategy.
Study characteristics
We included 1977 female patients with breast cancer. Eight studies [12, 15,16,17, 20, 22, 23, 25] concerned patients with early-stage cancer. Only one study [13] was concerned with locally advanced breast cancer, and six studies [14, 18, 19, 21, 25, 26] did not limit the patients’ cancer stage. All patients received anthracycline or trastuzumab. The mean age varied from 39.9 to 57.4 years between the studies. The baseline LVEF mean ranged between 54.3 and 68.7%. Eight studies reported adverse events [13, 14, 17, 19,20,21, 23, 25]. The characteristics of the 15 studies are reported in Table 1.
Outcomes
Fifteen studies reported LVEF and suggested a statistically significant higher LVEF in the treatment group (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813) (Fig. 2). Both ACEI and ARB are renin–angiotensin–aldosterone system (RAAS) inhibitors, so we combined them for analysis. Six studies reported LVEF in ACEI/ARB alone and suggested a statistically significant higher LVEF in the treatment group (χ2 = 136.62, I2 = 96.3%, p = 0.000; SMD 0.915, 95% CI 0.116 to 1.714) (Fig. 3). Thirteen studies also suggested that BB therapy preserved LVEF significantly better than placebo (χ2 = 41.03, I2 = 70.8%, p = 0.000; SMD 0.393, 95% CI 0.177 to 0.610) (Fig. 4). Three studies reported LVEF in ACEI/ARB combined with BB and suggested a statistically significant higher LVEF in the treatment group (χ2 = 3.02, I2 = 33.7%, p = 0.221; SMD 0.543, 95% CI 0.256 to 0.832) (Fig. 5).
Furthermore, ACEI/ARB or BB therapy suggested a statistically significant higher LVEF in the treatment group (χ2 = 155.43, I2 = 91.0%, p = 0.000; SMD 0.680, 95% CI 0.285 to 1.075) during anthracycline therapy (see Supplementary Fig. 1). During trastuzumab therapy, five studies also suggested a statistically significant higher LVEF in the treatment group (χ2 = 19.56, I2 = 69.3%, p = 0.003; SMD 0.300, 95% CI 0.062 to 0.538) (see Supplementary Fig. 2).
Adverse events
Eight studies reported adverse events [13, 14, 17, 19,20,21, 23, 24]. In seven of them, no adverse events occurred in both the test or control groups [13, 14, 17, 20, 21, 23, 24]. Avila et al. reported nine patients stopped the drug due to side effects, 6 (6.2%) in the placebo group and 3 (3.1%) in the carvedilol group (p = 0.30) [19].
Sensitivity analysis
Sensitivity analysis was conducted to investigate possible sources of heterogeneity by removing the data in sequence. The result indicated that the meta-analyses outcomes were stable, as shown in Supplementary Fig. 3.
Risk of bias
A total of 5 out of 15 studies were assessed to have a high risk of bias in overall bias. The overall trend in these assessments was the randomization process and the blinding of both participants and investigators (Supplementary Fig. 4). Five included studies were assessed as high risk in terms of deviations from intended interventions, for their open-label and placebo-controlled design. As noted by the authors, this can be partly explained by ethical considerations and informed consent to include late-phase breast cancer patients.
Overall quality of the evidence
Summary of the finding table was used to show the overall quality of the evidence for the primary outcome, LVEF. To present the results more intuitively, we summarize direct proof of all types of comparisons related to these outcomes in one table (Supplementary Table 4). The reasons to downgrade the quality of evidence are limitations of methodological quality of included trials according to the risk of bias assessment, statistical heterogeneity among included trials, and the small sample size. There were 13 (59.09%) moderate-quality evidence and 9 (40.91%) low-quality evidence.
Discussion
Based on the analysis of key outcome indicators, this study conducted a meta-analysis of 15 RCTs and found that prophylactic treatment with BBs and/or ACEI/ARB greatly enhances LVEF in comparison to anthracyclines or trastuzumab. The reduction of ventricular remodeling and anti-oxidative stress by these two medicines may be connected to the protective mechanism [29]. The lack of a substantial increase in LVEF in four studies using ACEI/ARB alone suggests that the favorable findings may be attributable to this early study [14]. The subgroup analysis’s findings also suggested that ACEI/ARB/BBs might offer protection against cardiotoxicity brought on by both anthracyclines and trastuzumab.
In recent years, more and more studies have focused on the cardiotoxicity of trastuzumab in combination with anthracyclines and have attempted to reduce it [30]. Doxorubicin liposomal has proven effective in reducing the harmful effects that doxorubicin can have on the heart, and new studies are still ongoing and gaining ground [31]. In many previous studies, the cardiotoxicity associated with trastuzumab was assumed to be transient and reversible with drug interruption or discontinuation. Recent data has partially revised this assumption, reporting a non-negligible incidence of long-term cardiotoxicity [32].
The recommended initial medications for treating heart failure are ACEI/ARB and BB. Research has indicated that ACEI/ARB and BB may have a positive impact on reducing the long-term health risks associated with anthracycline-induced cardiac dysfunction [12, 16]. Previous clinical studies have examined the treatment of doxorubicin-induced cardiotoxicity, but the patients involved had tumors other than breast cancer [33, 34]. Lewinter et al. [7], Elghazawy et al. [8], and Jeyaprakash et al. [35] published a similar meta-analysis. Elghazawy et al. not only focused on randomized controlled trials, but also included observational studies. However, they did not extract the breast cancer subgroup indicators from the original study. According to Lewinter et al., the use of ACEI/ARB therapy, regardless of whether it is combined with anthracycline or trastuzumab therapy, resulted in a slightly higher LVEF compared to a placebo, although the difference was not statistically significant. Jeyaprakash et al.’s study found that cardioprotective agents did not differ in their effect on LVEF according to Bayesian analysis. However, frequentist analysis suggested that ACEI/ARB and BB may offer significant cardio-protection. The inconsistency with the results of previous studies may be the different types and stages of the tumor and low-quality articles. The results still need to be further validated by high-quality RCT.
In clinical practice, it is crucial to establish multidisciplinary teams where cardiologists and oncologists work together to give the best possible care to oncology patients undergoing treatment with cardiotoxic agents. Based on our findings, there is no evidence to suggest that ACEI/ARBs are more effective than BBs in preventing a decrease in LVEF among patients undergoing breast cancer treatment.
This study also has some limitations. More substantial, high-quality, randomized, double-blind controlled trials are required to assess the clinical efficacy of beta-blockers and angiotensin receptor antagonists in the prevention of anthracycline-induced early cardiotoxicity, as the majority of the included studies only evaluated a small number of patients, and the heterogeneity of the unknown cause remains unexplained. Meanwhile, total heterogeneity ranged from moderate to high. The causes of the variations between the RCTs were not identified. Meanwhile, the results may be impacted by the method used to measure LVEF. However, the lack of sufficient studies makes it difficult to conduct a subgroup analysis on this topic.
Future research will also investigate the efficacy and safety of new medications as well as complementary therapies. For example, sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, outperforms standard therapy in the treatment of heart failure with reduced ejection fraction, but further research is required to determine its cardioprotective effects in the context of cardio-oncology. There is a randomized, placebo-controlled, double-blind, multi-center clinical trial [36] to see if sacubitril/valsartan given concurrently with early breast cancer therapy regimens comprising anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. Wang et al. [37], among others, have found that several herbal monomers have cardioprotective benefits in animal experiments.
Conclusion
When compared to placebo, ACEI/ARB and BB treatments can shield breast cancer patients from cardiotoxicity during trastuzumab and anthracycline-containing regimens, suggesting that both are helpful.
Availability of data and materials
Not applicable.
References
Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A et al (2020) Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol 31(2):171–190
Alvarez-Cardona JA, Ray J, Carver J, Zaha V, Cheng R, Yang E et al (2020) Cardio-oncology education and training: JACC council perspectives. J Am Coll Cardiol 76(19):2267–2281. https://doi.org/10.1200/JCO.2010.28.6450
Reeder-Hayes KE, Meyer AM, Hinton SP, Meng K, Carey LA, Dusetzina SB (2017) Comparative toxicity and effectiveness of trastuzumab-based chemotherapy regimens in older women with early-stage breast cancer. J Clin Oncol 35(29):3298–3305. https://doi.org/10.1200/JCO.2016.71.4345
Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G et al (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol 29(2):149–156
Macedo AVS, Hajjar LA, Lyon AR, Nascimento BR, Putzu A, Rossi L et al (2019) Efficacy of dexrazoxane in preventing anthracycline cardiotoxicity in breast cancer. JACC CardioOncol 1(1):68–79. https://doi.org/10.1016/j.jaccao.2019.08.003
Alexandre J, Cautela J, Ederhy S, Damaj GL, Salem JE, Barlesi F et al (2020) Cardiovascular toxicity related to cancer treatment: a pragmatic approach to the American and European cardio-oncology guidelines. J Am Heart Assoc 9(18):e018403. https://doi.org/10.1161/JAHA.120.018403
Lewinter C, Nielsen TH, Edfors LR, Linde C, Bland JM, LeWinter M et al (2021) 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. https://doi.org/10.1093/eurheartj/ehab843
Elghazawy H, Venkatesulu BP, Verma V, Pushparaji B, Monlezun DJ, Marmagkiolis K et al (2020) The role of cardio-protective agents in cardio-preservation in breast cancer patients receiving anthracyclines +/- trastuzumab: a meta-analysis of clinical studies. Crit Rev Oncol Hematol 153:103006. https://doi.org/10.1016/j.critrevonc.2020.103006
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 28(366):l4898
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical Research Ed) 336(7650):924–926. https://doi.org/10.1136/bmj.39489.470347.AD
Livi L, Barletta G, Martella F, Saieva C, Desideri I, Bacci C et al (2021) Cardioprotective strategy for patients with nonmetastatic breast cancer who are receiving an anthracycline-based chemotherapy: a randomized clinical trial. JAMA Oncol 7(10):1544–1549. https://doi.org/10.1001/jamaoncol.2021.3395
Wihandono A, Azhar Y, Abdurahman M, Hidayat S (2021) The role of lisinopril and bisoprolol to prevent anthracycline induced cardiotoxicity in locally advanced breast cancer patients. Asian Pac J Cancer Prev 22(9):2847–2853. https://doi.org/10.31557/APJCP.2021.22.9.2847
Lee M, Chung WB, Lee JE, Park CS, Park WC, Song BJ et al (2021) Candesartan and carvedilol for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin. Cancer Med 10(12):3964–3973. https://doi.org/10.1002/cam4.3956
Esfandbod M, Naderi M, Sadatnaseri A, Ahmadi A, Noroozi M, Joni SS (2021) Evaluation of the preventive effects of carvedilol on trastuzumab-induced cardiotoxicity in early-stage and locally advanced HER2-positive breast cancer patients. Int J Hematol Oncol Stem Cell Res 15(4):206. https://doi.org/10.18502/ijhoscr.v15i4.7475
Guglin ME, Tamura R, Krischer J, Munster P (2020) Trastuzumab induced cardiotoxicity: without prior anthracyclines, decrease in left ventricular ejection fraction is negligible. J Am Coll Cardiol 75(11):672. https://doi.org/10.1016/S0735-1097(20)31299-7
Moshkani Farahani M, Nourian S, Jalalian HR, Khosravi A, Salesi M (2019) Efficacy of treatment with carvedilol in preventing early-stage left ventricular dysfunction in patients with breast cancer candidated to receive trastuzumab using 2D speckle-tracking echocardiography. Iran Heart J 20(1):20–31
Cochera F, Dinca D, Bordejevic DA, Citu IM, Mavrea AM, Andor M et al (2018) Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer. Cancer Manag Res 10:2071–2081. https://doi.org/10.2147/CMAR.S166481
Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR Jr, das Dores Cruz F, Goncalves Brandao SM, Rigaud VOC et al (2018) Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol 71(20):2281–2290. https://doi.org/10.1016/j.jacc.2018.02.049
Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ et al (2017) Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol 35(8):870–877. https://doi.org/10.1200/JCO.2016.68.7830
Nabati M, Janbabai G, Baghyari S, Esmaili K, Yazdani J (2017) Cardioprotective effects of carvedilol in inhibiting doxorubicin-induced cardiotoxicity. J Cardiovasc Pharmacol 69(5):279–285. https://doi.org/10.1097/FJC.0000000000000470
Tashakori Beheshti A, Mostafavi Toroghi H, Hosseini G, Zarifian A, Homaei Shandiz F, Fazlinezhad A (2016) Carvedilol administration can prevent doxorubicin-induced cardiotoxicity: a double-blind randomized trial. Cardiology 134(1):47–53. https://doi.org/10.1159/000442722
Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW et al (2016) 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 37(21):1671–1680. https://doi.org/10.1093/eurheartj/ehw022
Boekhout AH, Gietema JA, Milojkovic Kerklaan B, van Werkhoven ED, Altena R, Honkoop A et al (2016) Angiotensin II-receptor inhibition with candesartan to prevent trastuzumab-related cardiotoxic effects in patients with early breast cancer: a randomized clinical trial. JAMA Oncol 2(8):1030–1037. https://doi.org/10.1001/jamaoncol.2016.1726
Elitok A, Oz F, Cizgici AY, Kilic L, Ciftci R, Sen F et al (2014) Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: a prospective randomized controlled study with six-month follow-up. Cardiol J 21(5):509–515. https://doi.org/10.5603/CJ.a2013.0150
Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M et al (2013) Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol 167(5):2306–2310. https://doi.org/10.1016/j.ijcard.2012.06.023
Guglin M, Krischer J, Tamura R, Fink A, Bello-Matricaria L, McCaskill-Stevens W et al (2019) Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J Am Coll Cardiol 73(22):2859–2868. https://doi.org/10.1016/j.jacc.2019.03.495
Guglin ME, Tamura R, Bello-Matricaria L, Fink A, Krischer J, Munster P (2019) Chemotherapy-induced cardiomyopathy: anthracyclines and trastuzumab require different approach to monitoring and prevention. J Am Coll Cardiol 73(9). https://doi.org/10.1016/S0735-1097(19)31514-1
Toyoda S, Haruyama A, Inami S, Arikawa T, Saito F, Watanabe R et al (2020) Effects of carvedilol vs bisoprolol on inflammation and oxidative stress in patients with chronic heart failure. J Cardiol 75(2):140–147. https://doi.org/10.1016/j.jjcc.2019.07.011
Keefe DL (2002) Trastuzumab-associated cardiotoxicity. Cancer 95(7):1592–1600. https://doi.org/10.1002/cncr.10854
Fang X, Wang H, Han D, Xie E, Yang X, Wei J et al (2019) Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci U S A 116(7):2672–2680. https://doi.org/10.1073/pnas.1821022116
Wang SY, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP et al (2014) Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival. Breast Cancer Res Treat 146(2):411–419. https://doi.org/10.1007/s10549-014-3029-0
Janbabai G, Nabati M, Faghihinia M, Azizi S, Borhani S, Yazdani J (2017) Effect of enalapril on preventing anthracycline-induced cardiomyopathy. Cardiovasc Toxicol 17(2):130–139. https://doi.org/10.1007/s12012-016-9365-z
Abdel-Qadir H, Ong G, Fazelzad R, Amir E, Lee DS, Thavendiranathan P et al (2017) Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis. Ann Oncol 28(3):628–633. https://doi.org/10.1093/annonc/mdw671
Jeyaprakash P, Sangha S, Low G, Yu C, Pathan F, Negishi K (2022) Cardioprotection against cardiac dysfunction from breast cancer chemotherapy: a Bayesian and frequentist network meta-analysis of randomised controlled trials. Eur Respir J 60(2579):2579
Mecinaj A, Gulati G, Heck SL, Holte E, Fagerland MW, Larsen AI et al (2021) Rationale and design of the prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardio-oncology 7(1):33. https://doi.org/10.1186/s40959-021-00115-w
Wang X, Li C, Wang Q, Li W, Guo D, Zhang X et al (2019) Tanshinone IIA restores dynamic balance of autophagosome/autolysosome in doxorubicin-induced cardiotoxicity via targeting Beclin1/LAMP1. Cancers (Basel) 11(7). https://doi.org/10.3390/cancers11070910
Funding
This work was supported by the National Natural Science Foundation of China (NSFC) (No. 81822049).
Author information
Authors and Affiliations
Contributions
YW proposed the concept of the study; YG and RTW drafted the manuscript. YW and YH contributed to revising the manuscript. YG, RTW, and JJ developed the search strategy and independently screened eligible studies, extracted data, assessed the quality of the included studies, and entered the data into Stata for data synthesis; HL arbitrated by discussion if disagreement occurred. All authors participated in the design of the study and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
10741_2023_10328_MOESM1_ESM.tif
Supplementary Fig. 1: Meta-analysis of the impact of concomitant treatment with ACEI/ARBs and BBs compared with placebo on left ventricular ejection fraction in patients treated with anthracyclines as a primary drug. SMD, standardized mean difference; CI, confidence interval (TIF 518 kb)
10741_2023_10328_MOESM2_ESM.tif
Supplementary Fig. 2: Meta-analysis of the impact of concomitant treatment with ACEI/ARBs and BBs compared with placebo on left ventricular ejection fraction in patients treated with trastuzumab as primary drug. SMD, standardized mean difference; CI, confidence interval (TIF 3471 kb)
10741_2023_10328_MOESM4_ESM.tif
Risk of bias summary: review authors' judgments about each risk of bias item for each included study. Fig. 9B Risk of bias graph: review authors' decisions about each risk of bias item presented as percentages across all included studies. (TIF 417 kb)
10741_2023_10328_MOESM8_ESM.docx
Supplementary table 4: The summary of finding tables for LVEF in patients who are receiving cardiotoxic therapy (DOCX 17 kb)
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Gao, Y., Wang, R., Jiang, J. et al. ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis. Heart Fail Rev 28, 1405–1415 (2023). https://doi.org/10.1007/s10741-023-10328-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10741-023-10328-z