The Prevention Of Beta-blockers And Angiotensin Antagonists On Early-onset Anthracyclines-induced Cardiotoxicity In Adult Patients:a Systematic Review And Meta-analysis

Background Antracyclines are the most effective antineoplastic agents in the treatment of numerous malignancies.Unfortunately,their use is limited by irreversible accumulative dose-dependent cardiotoxicity.Different cardioprotective agents have been studied to prevent this cardiotoxicity.Objectives We sought to assess the efficacy of beta-blockers and angiotensin antagonists in preventing early-onset anthracyclines-induced left ventricular dysfunction and cardiac events.Methods We searched relevant articles in Pub Med,EMBASE,the Cochrane Library,CNKI,Wanfang Date and Sinomed and supplemented by other search up to July 2017.According to the inclusion criteria and exclusion criteria,the two authors independently sifted the relevant documents,extracted the data and evaluated the methodological quality of the studies,and then analyzed the data by using R software for meta analysis.In meta analysis,the random effect model was used to calculate the mean difference of left ventricular ejection fraction(LVEF),the relative risk(RR)of cardiac events and the corresponding 95%confidence interval.Results 2892 potentially relevant studies were screened.Ten randomised controlled trials evaluating 757 patients treated with any type of anthracycline plus beta-blockers and/or angiotensin antagonists were included.Pooled analysis showed prophylactic treatment with beta-blockers and/or angiotensin antagonists improved post-chemotherapy left ventricular ejection fraction(LVEF)when compared to controls with estimated MD(95%CI)of-5.43(-9.08;-1.77),p=0.0036.Statistically significantheterogeneity was found in LVEF(I~2=93%,P<0.01).Although the cardiac events rate of 9.2%in the experimental group was lower than 25.8%in the control group after chemotherapy with estimated RR 0.45(95%CI:0.14,1.38;P=0.1619),the difference was not statistically significant.In an exploratory subgroup analysis,the benefit of experimental agents on LVEF preservation was prominent in patients treated with higher accumulative dose of anthracyclines,but not in the lower dose group.Conclusions Prophylactic treatment with beta-blockers and/or angiotensin antagonists can prevent early-onset anthracyclines-induced cardiotoxicity in adult patients,especially in patients treated with higher dose anthracyclines accumulative dose.More larger and high-quality's RCT are required to determine the clinical efficacy of beta-blockers and angiotensin antagonists for prevention ofearly-onset anthracyclines-induced cardiotoxicity.