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

BACKGROUND:
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.


OBJECTIVES AND DESIGN:
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.


METHODS:
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.


MAIN OUTCOME MEASURES:
The primary outcome was changes in left ventricular ejection fraction (LVEF). Secondary outcomes included cardiac event incidence and adverse events.


SAMPLE SIZE:
Nine RCTs were included, encompassing 869 patients (440 ACEI group, 429 control group).


RESULTS:
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.


QUALITY OF EVIDENCE:
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.


HETEROGENEITY:
High (I²=97%) for LVEF at 6 months.


CONCLUSION:
ACEIs prevent cardiotoxicity in the short term without increasing adverse events. More extensive trials are needed to confirm long-term benefits.


LIMITATIONS:
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.


REGISTRATION:
PROSPERO CRD42024555546.