CLINICAL PHARMACOLOGY / RESEARCH PAPER
Efficacy and harms associated with beta-blockers for cardiotoxicity in cancer patients undergoing chemotherapy: a systematic review and meta-analysis.
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1
University of Connecticut School of Pharmacy, United States
2
Oxford PharmaGenesis, Inc., United States
3
Unidad de Revisiones Sistemáticas y Meta-análisis (URSIGET), Vicerrectorado de Investigación, Universidad San Ignacio de Loyola., Peru
Submission date: 2024-02-04
Final revision date: 2024-05-17
Acceptance date: 2024-05-30
Online publication date: 2024-06-13
Corresponding author
Adrian V Hernandez
University of Connecticut School of Pharmacy, 69 N Eagleville Rd U-3092, 06269, Storrs, United States
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ABSTRACT
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.