title: Advances in the management of heart failure: the role of ivabradine.
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.
authors.affiliation: Charité - Universitätsmedizin Berlin; Protestant Geriatric Centre, Berlin.
authors.forename: Ursula
authors.initials: U
authors.lastname: Müller-Werdan
authors.affiliation: Department of Medical Affairs, Servier Deutschland GmbH, Munich.
authors.forename: Georg
authors.initials: G
authors.lastname: Stöckl
authors.affiliation: Department of Medicine III, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001683:Biological Clocks / Q000187:drug effects; D002908:Chronic Disease; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008875:Middle Aged; D018579:Patient Selection; D011788:Quality of Life; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine
keywords: If inhibitor; endotoxin; heart failure; heart rate; heart rate variability; ivabradine; pacemaker current inhibitor