Pharmacological interventions for preventing anthracycline-induced clinical and subclinical cardiotoxicity: A network meta-analysis of metastatic breast cancer

Abstract

Objective: Doxorubicin- and epirubicin-induced cardiotoxicities are life threatening for those suffering from breast cancer. Comparing the effects of different strategies on the prevention of these agent-induced cardiotoxicities remains unexplored.Data sources: A comprehensive review of clinical trials was performed on the prevention of epirubicin- and/or doxorubicin-induced cardiotoxicity in HER2-positive metastatic breast cancer patients. The reduction in ejection fraction was directed at evaluating cardiac toxicity.Data summary: Fourteen articles evaluated cardiotoxicity as a condition among 2945 individuals, evaluating doxorubicin, epirubicin, Liposomal Doxorubicin (LD), Pegylated Liposomal Doxorubicin (PLD), dexrazoxane plus doxorubicin or epirubicin, and Angiotensin-Converting Enzyme Inhibitors (ACEIs) plus doxorubicin. Pooled Odds Ratio (OR) of 0.043 with a 95% credible interval (CrI) between 0.005 and 0.22 indicated that the dexrazoxane plus epirubicin reduced the number of cardiac events compared with doxorubicin. Furthermore, doxorubicin and epirubicin represented the most effective interventions with a 52% probability of success. Also, the best treatment for reducing Congestive Heart Failure (CHF) was dexrazoxane plus epirubicin with a probability of 43%. For the Left Ventricular Ejection Fraction (LVEF) reduction outcome, ACEIs plus doxorubicin was ranked first with a success probability of 61.2% and they could significantly prevent the reduction in LVEF compared with LD, epirubicin, or doxorubicin.

Conclusion: Our data suggested that angiotensin-converting enzyme inhibitors and dexrazoxane plus epirubicin were the most effective interventions for preventing cardiotoxicity and CHF. However, ACEIs plus doxorubicin was the best treatment for preventing LVEF reduction.

Keywords: Cardioprotective therapy; HER-2 positive; cardiotoxicity; metastatic breast cancer; network meta-analysis.