Angiotensin converting enzyme inhibitors (ACEIs) for anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials.

Abstract

<h4>Background</h4>Anthracyclines are widely used in cancer treatment and cause dose-dependent cardiotoxicity 2 different by increasing oxidative stress and RAS activation. Angiotensin converting enzyme inhibitors (ACEIs) show promise in reducing this damage.<h4>Objectives and design</h4>This systematic review and meta-analysis evaluated the efficacy and safety of ACEIs in preserving left ventricular function and reducing cardiotoxicity associated with anthracycline therapy.<h4>Methods</h4>A comprehensive search of databases up to May 2024 included randomized controlled trials (RCTs) that assessed ACEIs to prevent cardiotoxicity. Random-effects meta-analysis was applied.<h4>Main outcome measures</h4>The primary outcome was changes in left ventricular ejection fraction (LVEF). Secondary outcomes included cardiac event incidence and adverse events.<h4>Sample size</h4>Nine RCTs were included, encompassing 869 patients (440 ACEI group, 429 control group).<h4>Results</h4>ACEIs significantly improved LVEF at six months (mean difference of 7.93%; 95% CI 3.18-12.67%; P=.001) but not at 12 months. Moreover, ACEIs were associated with non-statistically significant lower rates of heart failure and arrhythmia development compared to the control, with no significant differences noted in adverse events.<h4>Quality of evidence</h4>Evidence quality was high for short-term LVEF improvement and moderate-to-low for other outcomes. Egger's regression test indicated a low risk of publication bias for LVEF.<h4>Heterogeneity</h4>High (I²=97%) for LVEF at 6 months.<h4>Conclusion</h4>ACEIs prevent cardiotoxicity in the short term without increasing adverse events. More extensive trials are needed to confirm long-term benefits.<h4>Limitations</h4>The small number of RCTs and high heterogeneity limit the study. Inconsistent reporting of baseline cardiovascular factors and confounders also hindered accurate assessment of treatment effects.<h4>Registration</h4>PROSPERO CRD42024555546.