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Effect of Ivabradine on Endothelial Function in Patients with Stable Angina Pectoris: Assessment with the Endo-PAT 2000 Device

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Abstract

Introduction

Ivabradine has opened up new possibilities for treating stable angina and chronic heart failure by lowering heart rate. Ivabradine lowers heart rate by selectively inhibiting the I f current in the sinoatrial node. This study aimed to determine whether the decrease in heart rate achieved with ivabradine was accompanied by hemodynamic changes that might lead to an enhancement of endothelial function.

Methods

Thirty patients with stable angina pectoris were included in the study. Ivabradine (5 mg bid) was added to the recommended standard treatment. Endothelial function was assessed at baseline and after 3 months of ivabradine therapy, with an Endo-PAT 2000 device (Itamar Medical, Israel). This device was recently developed for the noninvasive assessment for endothelial dysfunction. We evaluated reactive hyperemia index (RHI), which reflects endothelial function, and augmentation index (AI), which provides an indication of arterial stiffness.

Results

The study population consisted of 25 (83.3%) men and five (16.7%) women. The mean age of the patients was 65.4 ± 6.7 years. Twenty-eight (93.3%) patients had a history of myocardial infarction (ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction), 23 (76.6%) had undergone revascularization (percutaneous coronary intervention or coronary artery bypass graft), 16 (53.3%) had type 2 diabetes mellitus, and 29 (96.6%) had arterial hypertension. The mean resting heart rate decreased significantly, from 77 ± 7 bpm at the start of the study to 65 ± 6 bpm after treatment (P < 0.0001). Endothelial function was found to have improved significantly after 3 months of ivabradine therapy. Mean RHI before treatment was 1.54 ± 0.30, suggesting probable endothelial dysfunction, whereas mean RHI at the end of the study was 1.83 ± 0.36 (P < 0.0001). AI also improved significantly on treatment, from 21 ± 20% to 10 ± 21% (P < 0.0001).

Conclusion

The addition of ivabradine to the treatment regimen of patients with stable angina pectoris both lowered heart rate and improved endothelial function. However, broader, randomized, double-blind, placebo-controlled clinical trials are required to confirm these findings.

Funding

Sponsorship for this study was funded by a VEGA grant no. 1/0858/11. Article processing charges were funded by Servier.

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Acknowledgments

Sponsorship for this study was funded by a VEGA grant no. 1/0858/11. Article processing charges were funded by Servier. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Disclosures

L Jedlickova, L. Merkovska, L. Jackova, M. Janicko, J. Fedacko, B. Novakova, D. Pella, A. Chmelarova, J. Majernik have nothing to disclose.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. 1st Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Šafárik University and Louis Pasteur University Hospital, Košice, Slovak Republic

    Lucia Jedlickova, Lucia Merkovska, Lucia Jackova, Martin Janicko, Jan Fedacko, Bozena Novakova & Daniel Pella

  2. Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovak Republic

    Anna Chmelarova

  3. Department of Medical Informatics, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovak Republic

    Jaroslav Majernik

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  1. Lucia Jedlickova
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Correspondence to Lucia Jedlickova.

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Jedlickova, L., Merkovska, L., Jackova, L. et al. Effect of Ivabradine on Endothelial Function in Patients with Stable Angina Pectoris: Assessment with the Endo-PAT 2000 Device. Adv Ther 32, 962–970 (2015). https://doi.org/10.1007/s12325-015-0253-x

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  • DOI: https://doi.org/10.1007/s12325-015-0253-x

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