Pharmacologic prevention of cardiotoxicity in breast cancer: a Bayesian network meta-analysis and meta-regression

Abstract

Cancer therapy related cardiac dysfunction (CTRCD) is a major concern in breast cancer patients, often reducing left ventricular ejection fraction (LVEF) and causing symptomatic heart failure. This study assessed the comparative effectiveness and safety of cardioprotective drugs in preserving LVEF during chemotherapy. Our database search, included Cochrane, PubMed, WOS, and SCOPUS, from inception to May 1st, 2024, to find randomized controlled trials (RCTs) that assessed the effectiveness and safety of cardioprotective drugs in breast cancer patients undergoing chemotherapy. Bayesian network meta-analysis and meta-regression were performed using the BUGSnet package in R studio version 4.4.2, applying a random-effects model, and mean differences (MD) with 95% credible intervals (CrI) were calculated. Eighteen RCTs involving 2,223 patients, met the inclusion criteria. Participants had a mean age was 48.78 (SD: 9.7). Spironolactone provided the greatest improvement in LVEF compared to placebo MD: 12.80; 95% CrI: 5.99 to 19.60, with the highest SUCRA value (97.84). Nebivolol ranked second (MD: 7.30; 95% CrI: 0.34 to 14.25; SUCRA: 81.67), while lisinopril + bisoprolol showed modest benefit (MD: 5.25; 95% CrI: -1.57 to 12.06; SUCRA: 69.43). Other agents, including rosuvastatin, bisoprolol, and candesartan, had variable effects with wide CrIs, and carvedilol and metoprolol showed limited efficacy. Model diagnostics confirmed stable convergence, good model fit, and no significant inconsistency across comparisons. Covariate-adjusted effect size from Bayesian network meta-regression identified hypertension prevalence and sample size as significant positive modifiers of treatment effect. Sensitivity analyses using a leave-one-out approach confirmed the robustness of the findings. Spironolactone and nebivolol are promising candidates for preserving LVEF in breast cancer patients undergoing cardiotoxic chemotherapy, while metoprolol showed minimal benefit. However, further studies with larger sample sizes and longer follow-up are essential to validate these results and assess long-term clinical outcomes.