Comparative Efficacy and Safety of Ivabradine vs. Beta Blockers in Heart Transplant Patients: A Systematic Review and Meta‐Analysis

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Background and Aims: Elevated resting heart rate in heart transplant (HTx) recipients due to graft denervation is associated with adverse outcomes. Ivabradine and beta blockers are commonly used for heart rate control post-HTx, but their comparative effectiveness and safety remain unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of ivabradine versus beta blockers in heart transplant recipients. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted in April 2025 across PubMed, Cochrane, Embase, and Google Scholar. Original studies, including cohort studies and randomized controlled trials (RCTs) comparing ivabradine to beta blockers in heart transplant patients were considered eligible. The primary outcome was mean heart rate. Secondary outcomes were left ventricular mass, left ventricular mass index, and ejection fraction; adverse events (phosphenes, dizziness, fatigue, sepsis); and mortality and survival. Risk of bias was assessed using Cochrane RoB 2 for the randomized trial and ROBINS-I for the non-randomized studies, and statistical analyses were performed using Review Manager 5.4. Results: = 0.05). Other efficacy parameters, including left ventricular mass, ejection fraction, and heart rate at 12 months, showed no significant differences. Adverse effects and survival outcomes were similar between groups. Sensitivity analysis revealed reduced heterogeneity when one high-bias study was excluded. Conclusion: Ivabradine may offer improved heart rate control and favourable changes in left ventricular mass index compared with beta blockers in heart transplant recipients, with a comparable safety and mortality profile. Given the small evidence base, the predominance of observational studies, and the substantial heterogeneity observed across several outcomes, these findings should be regarded as exploratory and hypothesis-generating. Further large-scale RCTs are warranted to confirm these findings and guide clinical decision-making.

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