Supplementary file 9_Protective effects of beta-blockers against anthracycline- and trastuzumab-related cardiotoxicity: a systematic review based on conventional and Bayesian network meta-analysis.xlsx

ObjectiveThis study aimed to systematically evaluate the efficacy of beta-blockers (BBs) in preventing left ventricular dysfunction (LVD) induced by anthracyclines and trastuzumab. It combines traditional meta-analysis with Bayesian network meta-analysis (NMA) to compare the cardiac protective effects of different BBs.
MethodsWe conducted a systematic literature search in databases such as PubMed, Web of Science, EMBASE, and the Cochrane Library to identify eligible randomized controlled trials (RCTs). Traditional meta-analysis and Bayesian NMA were used to evaluate the impact of BBs on left ventricular ejection fraction (LVEF) and cancer therapy-related cardiotoxicity events (CTRCE). The cumulative ranking probabilities (SUCRA) were used to rank the efficacy of different BBs. Data analysis was performed using STATA 16.0 and R 4.5.0 software.
ResultsA total of 19 RCTs were included for LVEF outcomes and 15 for CTRCE outcomes. For LVEF, BBs were superior to controls overall (WMD = 2.19, 95% CI 1.40–2.98; I2 = 93.5%). Subgroup analysis indicated consistent and greater improvement with bisoprolol and carvedilol. NMA-SUCRA ranking: bisoprolol 0.7696, carvedilol 0.6822, nebivolol 0.6023, metoprolol 0.2413, placebo 0.2047. For CTRCEs, BBs significantly reduced event risk (RR = 0.54, 95% CI 0.44–0.67; I2 = 41.4%). Subgroup analyses showed benefit with bisoprolol (RR = 0.28, 0.15–0.50), nebivolol (RR = 0.48, 0.27–0.86), and carvedilol (RR = 0.68, 0.53–0.87), while metoprolol did not reach significance (RR = 0.33, 0.07–1.56). Treatment-specific subgroups revealed significant benefit in anthracycline (RR = 0.52, 0.37–0.74) and combination regimens (RR = 0.58, 0.45–0.79), but not in trastuzumab monotherapy (RR = 0.16, 0.02–1.26). NMA-SUCRA ranking: bisoprolol 0.8085, metoprolol 0.7303, nebivolol 0.5124, carvedilol 0.3743, placebo 0.0745.
ConclusionBBs demonstrated robust protective effects in maintaining LVEF and reducing CTRCE risk, with bisoprolol showing the greatest efficacy, followed by carvedilol. The evidence supports prioritizing BBs during chemotherapy with individualized selection based on treatment regimen and patient profile. However, large-scale, multicenter RCTs with long-term follow-up are warranted to confirm long-term benefits and to explore combination strategies with other cardioprotective agents.
Systematic Review Registrationidentifier CRD420251233424.