Ivabradine

• ivabradine is a 'heart rate-reducing' agent able to slow heart rate, without complicating side-effects (1)
  • action results from a selective and specific block of pacemaker f-channels of the cardiac sinoatrial node (SAN) - investigation has shown that block by ivabradine requires
    • open f-channels
    • is use dependent
    • is affected by the direction of current flow
  • selective for the If current
    • ivabradine lowers heart rate at concentrations that does not affect other cardiac ionic currents
      • ivabradine blocks If channels in a concentration-dependent manner by entering the channel pore from the intracellular side
        • blockade is only possible when the If channel is open
          • magnitude of If inhibition is directly related to the frequency of channel opening
        • unlike other heart rate-lowering mechanisms, direct If blockade depends on the current driving force, as block dramatically increases across the voltage interval, and on sodium concentration in the surrounding milieu
          • ivabradine would be expected to be most effective at higher heart rates, where its clinical usefulness would also be greatest
    • specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply
    • ivabradine has no negative inotropic or lusitropic effects, thus preserving ventricular contractility - also it does not change any major electrophysiological parameters unrelated to heart rate
    • has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine

NICE have stated with respect to the use of ivabradine in heart failure:

• ivabradine is recommended as an option for treating chronic heart failure for people:
  • with New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction and
    
    
  • who are in sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and
    
    
  • who are given ivabradine in combination with standard therapy including betablocker therapy, angiotensin-converting enzyme (ACE) inhibitors and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated and
    
    
  • with a left ventricular ejection fraction of 35% or less
    
    
  • should only be initiated after a stabilisation period of 4 weeks on optimised standard therapy with ACE inhibitors, beta-blockers and aldosterone antagonists
    
    
  • should be initiated by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be carried out by a heart failure specialist, or in primary care by either a GP with a special interest in heart failure or a heart failure specialist nurse.

The summary of product characteristics must be consulted before prescribing this drug.

Reference:

1. Bucchi A et al. Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels. J Physiol. 2006 Apr 15;572(Pt 2):335-46.
2. NICE (November 2012).Ivabradine for treating chronic heart failure.