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Pharmacological interventions to prevent cardiotoxicity in patients undergoing anthracycline-based chemotherapy: a network meta-analysis.

  • 2025-09-03
  • Frontiers in cardiovascular medicine 12
    • Xiaoyu Liu
    • Ran Ding
    • Aihua Zhang

Study Design

Type
Systematic Review
Sample size
n = 858
Methods
We searched the EMBASE, Cochrane Library, PubMed, Web of Science, and Scopus databases from the beginning of each database to April 2024 and were limited to English-language documents. 28 randomized controlled trials involving 2,858 patients were finally included.

Background

This study evaluates the efficacy of various pharmacological therapies in mitigating the cardiotoxicity associated with anthracycline chemotherapy and furnishes contemporary, evidence-based guidelines and recommendations for clinical practice.

Methods

We searched the EMBASE, Cochrane Library, PubMed, Web of Science, and Scopus databases from the beginning of each database to April 2024 and were limited to English-language documents. The primary objective of this study is to assess the efficacy of cardioprotective drugs in preventing the reduction of left ventricular ejection fraction (LVEF) and the incidence of cardiac events. The secondary objective is to evaluate the impact of these drugs on reducing left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD), as well as on maintaining the ratio of peak mitral annular diastolic velocity to atrial contraction velocity (E/A ratio).

Results

54,852 studies were retrieved from five databases, and 28 randomized controlled trials involving 2,858 patients were finally included. Network Meta-analysis results showed that, compared to the control group, Spironolactone demonstrated the most significant improvement in (LVEF [MD = 12.10, 95% CI (7.50, 16.70)] and LVESD [MD = -5.00, 95% CI (-7.68, -2.32)]. For reducing cardiac events, Dexrazoxane [OR = 0.28, 95% CI (0.16, 0.50)] and Vitamin E combined with Levocarnitine [OR = 0.27, 95% CI (0.08, 0.90)] were the most effective interventions. In terms of diastolic function (E/A ratio), Nebivolol outperformed other β-blockers [MD = 0.23, 95% CI (0.09, 0.37)]. However, no intervention demonstrated a statistically significant effect on LVEDD.

Conclusion

According to the research findings, Spironolactone and Dexrazoxane significantly prevent the decline in LVEF and the occurrence of cardiac events compared to placebo or conventional chemotherapy, with statistical significance. This discovery provides valuable reference for the clinical prevention of anthracycline chemotherapy-induced cardiotoxicity, contributing to the optimization of treatment regimens, reduction of cardiac toxicity risks in patients, and improvement of prognosis.

Systematic review registration

PROSPERO (CRD42024567684).

Research Insights

  • L-Carnitine→Reduced Cardiac Event

    For reducing cardiac events, Dexrazoxane [OR = 0.28, 95% CI (0.16, 0.50)] and Vitamin E combined with Levocarnitine [OR = 0.27, 95% CI (0.08, 0.90)] were the most effective interventions.

    Effect
    Beneficial
    Effect size
    Large
  • Vitamin E→Reduced Cardiac Event

    For reducing cardiac events, Dexrazoxane [OR = 0.28, 95% CI (0.16, 0.50)] and Vitamin E combined with Levocarnitine [OR = 0.27, 95% CI (0.08, 0.90)] were the most effective interventions.

    Effect
    Beneficial
    Effect size
    Large
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