Efficacy of ivabradine in heart rate reduction after cardiac transplantation: Systematic review and meta-analysis

BACKGROUND Persistent sinus tachycardia affects up to 40% of patients after heart transplantation and is linked with graft dysfunction, impaired diastolic filling, and increased morbidity. Conventional rate-limiting therapies such as beta-blockers and calcium channel blockers are quite often contraindicated due to risks of bradyarrhythmia or hypotension. Ivabradine, a selective I(f) channel inhibitor, reduces heart rate (HR) without negative inotropic or hypotensive effects. AIM To evaluate the efficacy and safety of ivabradine in heart transplant recipients. METHODS A comprehensive search of PubMed, EMBASE, Scopus, Cochrane Library, and Google Scholar was conducted from inception to April 15, 2025. Eligible studies evaluated ivabradine in heart transplant recipient vs placebo or metoprolol, reporting HR, mortality, left ventricular mass (LVM), or safety. Data were independently extracted by two reviewers, and quality was assessed. Review Manager 5.4 performed pooled analyses using random-effects models. Mean differences (MD) or standardized MD (SMD) were calculated for continuous outcomes, and risk ratios for dichotomous outcomes. RESULTS Of 415 records identified, four studies comprising 264 patients (126 ivabradine, 138 control) met the inclusion criteria. Ivabradine significantly reduced resting HR compared with controls (MD = -11.06 beats per minute; 95%CI: -19.50 to -2.62; P < 0.00001; I 2 = 93%). Sensitivity analysis demonstrated consistent findings (SMD = -6.74; 95%CI: -9.23 to -4.24; I 2 = 0%). No significant difference in all-cause mortality was observed (MD = 0.52; 95%CI: 0.17-1.64; P = 0.27; I 2 = 85%). Pooled analysis of LVM revealed no significant effect of ivabradine (MD = -3.57 g; 95%CI: -29.21 to 22.08; P = 0.79; I 2 = 73%), with sensitivity analysis confirming neutrality. Adverse events were rare and mostly comparable between groups. CONCLUSION Ivabradine reduces HR effectively in heart transplant recipients without added adverse outcomes, supporting its use as safe and well-tolerated alternative when conventional agents are unsuitable. Despite potential clinical benefit, small sample size and heterogeneity the need for larger randomized trials to confirm long-term outcomes and establish ivabradine’s role in post-transplant care.