Ivabradine: Current and Future Treatment of Heart Failure

Basic Clin Pharmacol Toxicol. 2017 Aug;121(2):89-97. doi: 10.1111/bcpt.12784. Epub 2017 May 10.

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 AT1 receptor 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.

Publication types

  • Review

MeSH terms

  • Benzazepines / adverse effects
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors*
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Heart Failure, Diastolic / drug therapy
  • Heart Failure, Diastolic / metabolism
  • Heart Failure, Diastolic / physiopathology
  • Heart Failure, Systolic / drug therapy
  • Heart Failure, Systolic / metabolism
  • Heart Failure, Systolic / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Ivabradine
  • Membrane Transport Modulators / adverse effects
  • Membrane Transport Modulators / pharmacology
  • Membrane Transport Modulators / therapeutic use*
  • Practice Guidelines as Topic
  • Stroke Volume / drug effects

Substances

  • Benzazepines
  • Cardiotonic Agents
  • Cyclic Nucleotide-Gated Cation Channels
  • Membrane Transport Modulators
  • Ivabradine