title: Ivabradine: Current and Future Treatment of Heart Failure.
abstract: In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT1) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF.
authors.affiliation: Department of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Thorup
authors.affiliation: Department of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
authors.affiliation: Department of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
authors.affiliation: Department of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark.
authors.forename: Elise R
authors.initials: ER
authors.lastname: Hedegaard
mesh_terms: D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054144:Heart Failure, Diastolic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D054143:Heart Failure, Systolic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D049990:Membrane Transport Modulators; D000077550:Ivabradine