Heart rate reduction by I(f)-channel inhibition and its potential role in heart failure with reduced and preserved ejection fraction

Trends Cardiovasc Med. 2009 Jul;19(5):152-7. doi: 10.1016/j.tcm.2009.09.002.


Selective heart rate (HR) reduction by I(f)-channel inhibition is a recently developed pharmacological principle in cardiovascular therapy. Among these newly identified HR-lowering drugs, only ivabradine has now become approved for clinical use. I(f)-channel inhibition mainly reduces HR, thereby improving myocardial oxygen supply, energy balance, and cardiac function. Ivabradine was well tolerated and revealed a good safety profile in the investigated study populations. The guiding experimental and clinical results of I(f)-channel inhibition were compared to those of beta-blockade as a HR reducing principle as well as cornerstone of heart failure standard therapy. Beside its use in therapy of coronary artery disease, I(f)-channel inhibition potentially exhibits beneficial effects in systolic and diastolic heart failure as well. Therefore, hemodynamic effects of ivabradine and its limitations in heart failure together with the biological impact of HR reduction will be considered in this context. Because no clinical data with specific heart-rate-reducing agents are available in heart failure patients until now, the prospective significance of I(f)-channel inhibition can only be speculated on. However, the presented results and considerations are encouraging: ivabradine may play a therapeutic role in the future protecting left ventricular function and structure from early deterioration in heart failure with reduced and preserved ventricular ejection fraction.

Publication types

  • Review

MeSH terms

  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Heart Rate / drug effects*
  • Hemodynamics / drug effects
  • Humans
  • Ivabradine
  • Stroke Volume / drug effects*
  • Treatment Outcome
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects


  • Benzazepines
  • Cardiotonic Agents
  • Ivabradine