August 6, 2025Open Access

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

PVPinyadapat VacharanukrauhFederation University KMKyle J. MillerAustralian Regenerative Medicine Institute SASheikh Mohammad AlifKhulna University

Key Points

Mineralocorticoid receptor antagonists showed the strongest cardioprotective effect in preventing cardiotoxicity.
The analysis covered 31 randomized controlled trials involving over 3,200 breast cancer patients and their outcomes.
Trimetazidine and dexrazoxane also demonstrated significant benefits, while β-blockers showed potential but more uncertainty.
A lack of direct head-to-head trials highlights the need for further studies to compare the effectiveness of these cardioprotective agents.

Abstract

Abstract 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.

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