Pharmacological interventions for anthracycline-induced cardiotoxicity in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to systematically assess the efficacy of cardioprotective agents in preventing anthracycline-induced cardiotoxicity in patients with breast cancer using a comprehensive network meta-analysis (NMA).

Methods: This study included patients with breast cancer undergoing anthracycline-based chemotherapy. Randomized controlled trials (RCTs) published before March 2020 were identified through systematic searches in MEDLINE, Cochrane CENTRAL, Web of Science, and CINAHL. The primary outcome was left ventricular ejection fraction (LVEF), assessed using cardiac magnetic resonance imaging, multigated radionuclide angiography, or echocardiography. The NMA integrated direct and indirect comparisons to estimate the relative effectiveness of pharmacological interventions.

Results: The systematic review included 31 RCTs with 3,228 participants, whereas the NMA synthesized 25 effect sizes from 15 RCTs. Mineralocorticoid receptor antagonists (MRAs) [standardized mean difference (SMD): -1.78, 95% confidence interval (CI): -2.81 to -0.75] and trimetazidine (SMD: -1.12, 95%CI: -2.32 to -0.09) exhibited the most substantial cardioprotective effects. Dexrazoxane (SMD: -0.53, 95%CI: -1.90 to -0.02) and β-blockers (SMD: -0.34, 95%CI: -0.70 to 0.02) showed potential benefits, albeit with greater uncertainty. Direct comparisons showed that dexrazoxane was more effective than β-blockers (SMD: -1.25, 95%CI: -2.22 to -0.48), with mineralocorticoid receptor antagonists (MRAs) outperforming both. Despite heterogeneity and potential publication bias, mineralocorticoid receptor antagonists (MRAs) and trimetazidine consistently ranked as the most effective interventions. LVEF findings confirmed the cardioprotective benefits of β-blockers, ARBs, ACE inhibitors, and dexrazoxane.

Conclusions: RCT evidence suggested that cardioprotective drugs effectively mitigate anthracycline-induced LVEF decline. However, the lack of direct head-to-head trials limits definitive conclusions on comparative efficacy, warranting trials in patients with lower baseline LVEF to optimize cardioprotective strategies.