Ivabradine in Heart Transplant Recipients With Sinus Tachycardia: A Systematic Review and Meta-Analysis

Abstract

Sinus tachycardia is common after heart transplantation (HTx) and may worsen graft function via increased oxygen demand and remodeling. Ivabradine, a selective If channel inhibitor, lowers heart rate independently of sympathetic activity. This meta-analysis evaluates its efficacy and safety versus standard care in HTx recipients. A comprehensive search of PubMed, Embase, WoS, Scopus, and Cochrane was conducted through September 2025. Eligible studies included randomized and non-randomized comparative trials. Data were pooled with a random-effects model to estimate mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes. Six studies, including 852 adult HTx recipients, were included. Ivabradine consistently reduced HR across all time points. Statistical significance was reached at 24 months (MD -16.82 bpm; P=0.04) and 36 months (MD -12.94 bpm; P=0.04). A significant reduction was observed in LVMI (MD -11.10 g/m2; 95% CI -17.15 to -5.06; P<0.05; I^2=0%). While LVM and LVEF showed trends toward improvement at final follow-up (MD = -11.23 for LVM and +2.94% for LVEF), neither reached statistical significance (P = 0.06 and P = 0.48, respectively). No significant differences were found between the ivabradine and control groups regarding all-cause mortality (RR 1.16 at final follow-up; P=0.90), graft rejection (RR 1.14; P=0.87), or systolic blood pressure (MD 0.50 mmHg; P=0.83). Ivabradine lowers heart rate after heart transplantation but shows no clear benefit on mortality, rejection, or ejection fraction. It does not significantly affect blood pressure, supporting its tolerability, particularly when beta-blockers are not tolerated.