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

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart transplant recipients (n=263). Intervention: Ivabradine vs. Beta blockers (Metoprolol). Primary outcome: Mean heart rate at 24 months (MD -11.70, 95% CI -23.36 to -0.05, p=0.05).

Q: What does this research mean for the field?

Ivabradine may offer improved heart rate control and favorable changes in left ventricular mass index compared with beta blockers in heart transplant recipients, while maintaining a comparable safety and mortality profile. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ahmad Hassan; Maaz Amir; Mehrab Naeem; Eshah Fatima Ali; Ubaid Ullah; Muhammad Asad Jahangir; Muhammad Umer Hassaan; Rafia Aman; Hafiza Rafia Rifat; Mohammad Faez Nazir; Muhammad Numan Awais; Areeba Alizai; Sidra Gul; Adeena Asif

doi:10.1002/hsr2.73068

August 1, 2026Health Science ReportsOpen Access

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

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Key result

Ivabradine reduces heart rate ~12 bpm more than beta blockers in heart transplant recipients.

MD -11.70
95% CI -23.36 to -0.05
P=0.05
n=263

Figures

Why the study?

Ivabradine and beta blockers are commonly used to treat elevated resting heart rate post-heart transplant, but their comparative effectiveness and safety remain unclear.

Does ivabradine improve heart rate control and cardiac remodeling compared to beta-blockers in heart transplant recipients?

Key Points

To evaluate the comparative efficacy and safety of ivabradine versus beta blockers for heart rate control and cardiac remodeling in heart transplant recipients.
Conducted a systematic search across PubMed, Cochrane, Embase, and Google Scholar through April 2025 following PRISMA guidelines.
Included 4 studies (1 randomized controlled trial and 3 cohort studies from Germany and Brazil) comparing ivabradine to beta blockers (metoprolol) in heart transplant patients.
Assessed change in mean heart rate as the primary outcome, alongside secondary outcomes including left ventricular mass, left ventricular mass index, ejection fraction, adverse events, and survival.
Ivabradine significantly reduced left ventricular mass index compared to metoprolol (MD −8.82, 95% CI −14.05 to −3.59, p = 0.001), while left ventricular mass at 24 months (MD −13.18 g, 95% CI −39.56 to 13.20, p = 0.33) and ejection fraction (MD 3.03%, 95% CI −3.01 to 9.07, p = 0.33) showed no significant differences.
Mean heart rate was not significantly different between groups at 12 months (MD −14.09, 95% CI −37.42 to 9.23, p = 0.24), while at 24 months the reduction approached significance (MD −11.70, 95% CI −23.36 to −0.05, p = 0.05).
No significant differences occurred between groups for all-cause mortality (OR 0.44, 95% CI 0.04–4.61, p = 0.50), 2-year survival (OR 4.27, 95% CI 0.40–45.30, p = 0.23), phosphenes (OR 6.91, 95% CI 0.82–58.5, p = 0.08), or dizziness (OR 0.31, 95% CI 0.08–1.14, p = 0.08).

Study Design

Type

Meta-Analysis (n=263)

Structured PICO

Does ivabradine improve heart rate control and cardiac remodeling compared to beta-blockers in heart transplant recipients?

P

Population

263 heart transplant recipients from 4 studies (3 observational, 1 RCT) followed for up to 24 months to compare the efficacy and safety of ivabradine versus beta blockers.

I

Intervention

Ivabradine

C

Comparator

Beta-blockers (specifically metoprolol in the included studies)

O

Outcome

Mean heart rate (assessed at 12 and 24 months)surrogate

Main Result

Mean Difference: -11.7 (95% CI -23.36–-0.05)

p-value: p=0.05

In heart transplant recipients, ivabradine provides comparable heart rate control and safety to beta-blockers, while potentially offering superior improvements in left ventricular mass index.

Limitations

Small number of eligible studies (only 4)
Predominance of non-randomized observational studies, limiting internal validity
Considerable heterogeneity in study design, follow-up durations, and medication regimens
Small number of included studies precluded subgroup analyses and formal assessment of publication bias
Variability in ivabradine and beta-blocker dosing may have influenced outcomes
Small evidence base (only 4 studies included)
Predominance of observational studies (3 out of 4)
Substantial heterogeneity observed across several outcomes
Variability in the dosing of both ivabradine and beta-blockers across studies

Implication

Supports ivabradine for sustained heart rate reduction versus beta-blockers in heart transplant recipients; extends follow-up to 24 months but heterogeneity limits certainty.

Abstract

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. 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.

Discussion

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Cite This Study

Hassan et al. (2026) conducted a meta-analysis in Heart transplant recipients (n=263). Ivabradine vs. Beta blockers (Metoprolol) was evaluated on Mean heart rate at 24 months (MD -11.70, 95% CI -23.36 to -0.05, p=0.05). Ivabradine reduced mean heart rate at 24 months compared to beta blockers in heart transplant recipients (MD -11.70), though with substantial heterogeneity.

synapsesocial.com/papers/6a89b5220e1a8f7244fd56f2 https://doi.org/10.1002/hsr2.73068

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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