Cardioprotective strategies of ACEi/ARBs and beta-blockers against anthracycline-induced cardiotoxicity in pediatric cancer survivors: a systematic review

Anthracyclines are routinely used in pediatric oncology but cause dose-dependent cardiotoxicity that compromises long-term survival. Neurohormonal agents such as ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), and beta-blockers have been suggested as preventive or therapeutic agents, yet evidence in children remains limited. Present review aimed to synthesize available data on their efficacy and safety among this population. A systematic search of PubMed, Scopus, and Web of Science was conducted from inception to August 2025. Eligible studies included pediatric cancer survivors exposed to anthracyclines who received ACEi, ARBs, or beta-blockers with reported cardiac outcomes. Data extraction and risk-of-bias assessments were performed independently by two reviewers. Findings were synthesized narratively owing to study heterogeneity. Sixteen studies met inclusion criteria, comprising nine RCTs, three observational studies, two case series, and two case reports. ACEi, mainly enalapril and captopril, were associated with attenuation of left ventricular ejection fraction (LVEF) decline and reduced biomarker elevations, although long-term benefits were inconsistent and side effects such as hypotension were reported. Beta-blockers, particularly carvedilol, improved ventricular function, strain indices, and clinical symptoms in several studies, though the largest trial (PREVENT-HF) did not show significant benefit on primary remodeling outcomes, except in high-risk subgroups. Overall, the evidence suggests that while preventive use of ACEi/ARBs and beta-blockers shows more consistent benefits, findings regarding their role in reversing established cardiotoxicity remain variable and should be interpreted cautiously. ACEi/ARBs and beta-blockers showed promise in preventing or mitigating anthracycline-induced cardiotoxicity among children, with consistent benefits on surrogate outcomes but uncertain durability and survival impact. Early initiation and targeted use in high-risk patients appear most advantageous, underscoring the need for large biomarker-guided trials to refine prevention strategies.