Efficacy and harms associated with beta-blockers for cardiotoxicity in cancer patients undergoing chemotherapy: a systematic review and meta-analysis.

Introduction In patients with breast cancer and lymphoma, anthracyclines are associated with early and late dose-related cardiotoxicity. We systematically evaluated efficacy and harms of the use of beta-blockers in breast cancer and lymphoma patients undergoing chemotherapy. Material and methods We searched five engines, and pre-prints until October 10, 2022, for randomised controlled trials (RCTs) evaluating beta-blockers for anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Primary outcomes were all-cause mortality, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic diameter (LVEDD, LVESD), peak E’ velocity, E/A ratio, E/e’ ratio, NT-pro BNP levels. Secondary outcome was heart rate. Inverse variance random effect meta-analyses were performed, and we used GRADE methods to assess quality of evidence (QoE). Results Twelve RCTs were selected (n=1,794), seven RCTs evaluated carvedilol. Mean ages were 39 to 52 years-old, 88.5% were women; 79.4% had breast cancer, and 11.5% lymphoma. The evidence was very uncertain about the effect of beta-blockers on all-cause mortality (RR 0.87, 95%CI 0.55 to 1.37, 12 RCTs, I2=0%, very low QoE), LVEF (MD 2.73%, 95%CI -0.45% to 5.92%, 12 RCTs, I2=93%, very low QoE), and heart rate (MD -9.14 bpm, 95%CI -15.02 to -3.26, two RCTs, I2=87%, very low QoE) vs. controls. Beta-blockers likely reduced NT-pro BNP levels slightly (MD -15.35 pg/mL, 95%CI -22.39 to -8.31, two RCTs, I2=0%, moderate QoE). There were no effects on other outcomes, all with very low QoE. Conclusions Prophylactic use of beta-blockers for cardioprotection had little to no effect on all-cause mortality, LVEF or cardiac function outcomes in cancer patients undergoing anthracycline therapy.