Role of ivabradine for anthracycline-induced cardiotoxicity: a meta-analysis

Anthracyclines are widely used anticancer agents but are limited by dose-dependent cardiotoxicity. Ivabradine selectively reduces heart rate without negative inotropy and may offer cardio protection in cancer patients, though its efficacy in anthracycline-induced cardiotoxicity (AIC) remains unclear.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ivabradine versus placebo in adult patients receiving anthracycline therapy. PubMed, Cochrane Central, Embase, Web of Science, Google Scholar, Scopus and ClinicalTrials.gov, and reference lists were searched through August 2025. Outcomes included left ventricular ejection fraction (LVEF), heart rate, blood pressure, NT-proBNP, and strain-based parameters. Risk of bias was assessed with the Cochrane RoB 2 tool.

Three RCTs (n = 210) met inclusion criteria. Ivabradine showed no significant effect on LVEF (MD 0.32%, 95% CI - 0.90 to 1.54; p = 0.61) or NT-proBNP. Heart rate reduction was directionally favorable but not statistically significant (MD - 4.11 bpm, 95% CI - 8.69 to 0.46; p = 0.08). Systolic and diastolic blood pressure were unchanged. Strain-based outcomes were inconsistently reported, precluding pooled analysis.

Given the limited sample size, heterogeneity, and variability in endpoint definitions, current evidence is insufficient to establish a definitive cardioprotective role for ivabradine in AIC. Larger, rigorously designed trials with standardized imaging and biomarker endpoints are needed to determine its role.