Prophylactic ACE inhibitor use reduced incidence of ≥10% LVEF decline from 67% to 50% and improved 12-month survival probability from 34% to 54%, but protective effect was not statistically significant after adjustment (HR 0.60, P=0.051).
Systematic Review (n=111)
Do ACE inhibitors, ARBs, or beta-blockers prevent or mitigate anthracycline-induced cardiotoxicity in pediatric cancer survivors?
ACE inhibitors, ARBs, and beta-blockers show promise in mitigating anthracycline-induced cardiotoxicity in pediatric cancer survivors by improving surrogate echocardiographic and biomarker outcomes, though large biomarker-guided trials are needed to confirm long-term clinical benefits.
Effect estimate: HR 0.60 (95% CI 0.36 to 1.00)
Absolute Event Rate: 50% vs 67%
p-value: p=0.051
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.
Sattarpour et al. (2026) conducted a systematic review in Pediatric patients with malignant bone tumors (osteosarcoma and Ewing sarcoma) treated with anthracycline-based chemotherapy (n=111). ACE inhibitors (prophylactic) vs. Control group without ACE inhibitor therapy was evaluated on Incidence of ≥10% reduction in left ventricular ejection fraction (LVEF) and event-free survival (EFS) based on LVEF (HR 0.60, 95% CI 0.36 to 1.00, p=0.051). Prophylactic ACE inhibitor use reduced incidence of ≥10% LVEF decline from 67% to 50% and improved 12-month survival probability from 34% to 54%, but protective effect was not statistically significant after adjustment (HR 0.60, P=0.051).