Ivabradine, a selective If inhibitor already investigated for its effects in coronary artery disease and left ventricular dysfunction, significantly lowers the risk of heart failure, according to results of the SHIFT study (Systolic Heart failure treatment with the If inhibitor ivabradine Trial).

Ivabradine binds to If channels found in the sinus node, the heart's pacemaker. If channels generate an electrical impulse that causes the heart to contract so that blood can be pumped to the lungs and the rest of the body. By binding to these If channels, ivabradine thus slows the rate at which the heart beats.

Resting heart rate is known to be inversely related to prognosis in many cardiovascular diseases and is recognized to have independent prognostic value in heart failure. The SHIFT study was designed to investigate if ivabradine's inhibition of sino-atrial If current and had a beneficial effect in patients with a heart rate above 70 beats per minute.

"Heart failure is normally associated with high mortality risk", said principal investigator Professor Michel Komajda, head of Cardiovascular and Surgical departments at the Pitie Salpetriere hospital in Paris. "Approximately 50% of patients die after five years, and they endure recurrent and lengthy hospitalizations as well as a decline in the quality of life. Despite the introduction of new treatments over the last 20 years resulting from significant medical advances, the prevalence of heart failure is actually increasing worldwide, particularly as people are living to an older age."

More than 6500 patients with heart failure were enrolled in the trial, and randomized to either ivabradine or placebo. Heart failure was defined as NYHA class II - IV, left ventricular ejection fraction of 35% or less, and a prior hospitalization for worsening heart failure within the previous 12 months. The patients were all receiving currently recommended heart-failure medication, and all had a heart rate of at least 70 bpm.

Results showed that ivabradine significantly reduced the number of cardiovascular deaths or heart-failure hospitalizations (the primary endpoint of the study) by 18% (p<0.0001). It was also associated with a reduction of 26% in heart-failure events leading to hospitalization or death. Average follow-up time was 23 months.

"This is a major finding," said Professor Komajda. "The 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 hospitalization 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 SHIFT study results were presented during a Hotline session at the 2010 European Society of Cardiology Congress and simultaneously published online in the Lancet.

Authors of the study are Michel Komajda, Karl Swedberg, Michael Boehm, Jeffrey S. Borer, Ian Ford, Ariane Dubost-Brama, Guy Lerebours and Luigi Tavazzi.