Efficacy of beta-blockers in preventing cardiotoxicity in breast cancer patients receiving anthracyclines: a GRADE-assessed systematic review and meta-analysis with trial sequential analysis

Abstract

Anthracycline-induced cardiotoxicity remains an important complication in patients with breast cancer receiving systemic therapy, and effective preventive strategies remain limited. We conducted a systematic review and meta-analysis to evaluate the cardioprotective effects of beta-blockers in anthracycline-treated breast cancer patients. Following PRISMA guidelines, Pubmed, Web of Science, CINAHL, and Cochrane were systematically searched, and the protocol was preregistered on PROSPERO (CRD420261366946). The primary outcome was left ventricular ejection fraction (LVEF), while the secondary outcome was E/A ratio. Certainty and robustness of the evidence were assessed using GRADE approach and trial sequential analysis (TSA). A meta-analysis was performed using R version 4.6.0, and heterogeneity was assessed using I 2 statistics. A total of 8 studies including 772 patients were analyzed. Beta-blocker therapy was associated with significant preservation of LVEF vs. placebo or standard care (MD, 2.85; 95% CI, 0.58–5.12; p  = 0.02; I 2 95%). No significant improvement was observed for E/A ratio (MD, 0.10; 95% CI, −0.12 to 0.31; p  = 0.25; I 2 69.7%). However, sensitivity analysis resulted in a statistically significant pooled effect (MD = 0.16, 95% CI: 0.03 to 0.29, p  = 0.01; I 2  = 35.9%). TSA showed that the Z-curve crossed the monitoring boundaries favoring beta-blockers for LVEF; however, the required information size (RIS = 1,785) was not reached. Beta-blockers were associated with preservation of systolic function in anthracycline-treated breast cancer patients. However, no significant benefit was observed for E/A ratio, and evidence regarding diastolic protection remains inconclusive. Larger, high-quality RCTs are needed to confirm these findings. identifier CRD420261366946.