A new agent that slows heart rate by inhibiting sodium-potassium channels found in the sino-atrial node of the heart appears to benefit heart failure patients when added on to current therapy. The agent, ivabradine, was associated with a significant 18% drop in the composite rate of cardiovascular death or heart-failure hospitalisation, compared with placebo, in the SHIFT trial. It was also associated with a reduction of 26% in heart-failure events leading to hospitalisation or death.

SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) involved 6,500 patients with New York Heart Association (NYHA) class II – IV heart failure, left ventricular ejection fraction of 35% or less, and a prior hospitalisation for worsening heart failure within the previous 12 months. They were randomised to either ivabradine or placebo. All patients were receiving currently recommended heart failure medication, and had a heart rate of at least 70 bpm.

Principal investigator Professor Michel Komajda (Pitié Salpetrière Hospital, Paris, France) said: “These results have been achieved in addition to the effects of other medications. Heart failure and high heart rates are extremely common so it is very good news for patients and doctors that, even when using the best current drug treatment available, ivabradine further reduces the risk of death or hospitalisation by over 25%. Ivabradine has only one known cardiac action, so this opens a fascinating area of research. The SHIFT trial has demonstrated, for the first time, that reducing heart rate alone is beneficial for patients with heart failure.”

The main side-effect of ivabradine is bradycardia (slow heart rate), which occurred in 10% of patients in this study, leading to withdrawal in 1% of patients receiving the drug.

The main concern voiced about the SHIFT trial was that patients might not have been on optimal doses of beta blockers and the benefits brought about by ivabradine may also have been seen by raising the beta-blocker dose. But designated discussant of the trial, Dr Inder Anand (University of Minnesota, USA), dismissed these concerns, noting that higher doses of beta blockers have not been shown to reduce heart rate further and, in the real world, physicians are unable to increase doses of beta blockers to target levels because of concerns about side effects.