Efficacy of Cardioprotective Drugs in Cancer Patients Receiving Anthracyclines: A Pairwise Meta-Analysis and Network Meta-Analysis.

Abstract

Anthracyclines are cornerstone chemotherapeutic agents for several cancers but carry a substantial risk of cardiotoxicity. Multiple cardioprotective drugs have been investigated to prevent cardiac dysfunction in patients receiving anthracycline-based chemotherapy. This study evaluated and ranked the cardioprotective effects of these agents using network meta-analysis. A comprehensive search of PubMed, Cochrane, Scopus, and Web of Science from inception to September 22, 2024 identified randomized clinical trials and cohort studies assessing cardioprotective agents in cancer patients treated with anthracyclines. Interventions included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and metformin. The primary outcome was change in left ventricular ejection fraction (LVEF). Secondary outcomes were left ventricular end-diastolic diameter (LVEDD), chemotherapy-related cardiac dysfunction (CTRCD), heart failure (HF), HF hospitalization, and all-cause mortality. Thirty-five studies were included, comprising 31 randomized controlled trials and 4 retrospective studies. Overall, cardioprotective therapy significantly improved LVEF, reduced CTRCD, all-cause mortality, HF incidence, and LVEDD, but had no significant effect on HF hospitalization. Subgroup and network meta-analyses showed that ACEIs plus beta-blockers, beta-blockers alone, statins, and ACEIs significantly improved LVEF versus controls, with ACEIs ranking highest. For CTRCD prevention, statins and beta-blockers significantly reduced risk, whereas ACEIs plus beta-blockers had the most favorable ranking. For mortality, the available retrospective SGLT2 inhibitor studies suggested an association with lower risk; however, because no randomized anthracycline-specific SGLT2 inhibitor trials were available and follow-up duration differed from the RCT evidence for other agents, this finding should be considered hypothesis-generating rather than definitive comparative evidence. ACEIs, beta-blockers, and statins appear effective for preserving cardiac function during anthracycline therapy. Treatment rankings, particularly for outcomes supported by sparse or observational evidence, should be interpreted cautiously, and further randomized trials are needed, particularly to evaluate SGLT2 inhibitors.