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Advances in the management of heart failure: the role of ivabradine

Authors Müller-Werdan U, Stöckl G, Werdan K

Received 30 May 2016

Accepted for publication 12 September 2016

Published 17 November 2016 Volume 2016:12 Pages 453—470

DOI https://doi.org/10.2147/VHRM.S90383

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 5

Editor who approved publication: Professor Daniel Duprez


Ursula Müller-Werdan,1,2 Georg Stöckl,3 Karl Werdan4

1Charité – Universitätsmedizin Berlin, 2Protestant Geriatric Centre, Berlin, 3Department of Medical Affairs, Servier Deutschland GmbH, Munich, 4Department of Medicine III, University Hospital Halle (Saale), Martin-Luther-University Halle‑Wittenberg, Halle (Saale), Germany

Abstract: A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF.

Keywords: heart failure, endotoxin, If inhibitor, ivabradine, pacemaker current inhibitor, heart rate, heart rate variability

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