INTRODUCTION: Anthracycline is a cornerstone in the treatment of various cancers. One major limitation to its use is cardiotoxicity. Renin angiotensin system (RAS) inhibitors have been shown to attenuate myocardial injury, initial data is promising in its use as prophylaxis for anthracyclineinduced cardiotoxicity. The aim of the study is to determine effectiveness of prophylactic RAS inhibitors in preventing anthracycline-induced cardiotoxicity and adverse cardiac events among adult cancer patients

METHODS: Systematic search of databases PUBMED, MEDLINE, EMBASE, and CENTRAL was done. Selection criteria were: 1) randomized controlled trials (RCT) 2) adult cancer patients with normal ejection fraction and without heart failure symptoms 3) RAS inhibitors as prophylaxis versus placebo 4) development of cardiac events, all-cause mortality and left ventricular ejection fraction (LVEF) reduction as outcomes. Two reviewers independently assessed the trials. Disagreements were resolved with a third reviewer. Test for effect of intervention, heterogeneity, trial quality and risk of bias were assessed using the Cochrane Review Manager Software version 5.3.

RESULTS: Five RCTs involving 530 adult patients, with average age of 50± two years old, and average follow-up from six months to three years were included. Combined clinical outcomes of heart failure, cardiac events and all-cause mortality showed an RR of 0.27[95%CI 0.18, 0.40],p<0.00001, in favor of RAS inhibitors. There is same benefit in LVEF preservation with mean difference of 4.37%[95%CI 1.20, 7.55;p=0.007]. Exploratory subgroup analysis showed significant benefit in LVEF preservation with combined RAS inhibitor and beta-blocker, with mean difference of 2.45%[95%CI 1.27, 3.63]. There is overall significant heterogeneity (I2=95%). Excluding one article with high-risk population, after sensitivity analysis, showed same benefit but reduced heterogeneity.

CONCLUSION: Renin angiotensin system (RAS) inhibitors may be used as prophylaxis for cardiotoxicity. As prophylaxis, it reduced the clinical outcome of cardiac events, heart failure, and all-cause mortality among cancer patients needing anthracycline. Combined RAS inhibitor and betablocker limits LVEF reduction.