The Lancet has published the results of the SHIFT study which aimed to assess the effect of heart rate reduction using ivabradine (Procoralan®) in patients with heart failure. The results of this study have been reported in the general media (BBC).
The study recruited and treated 6,505 participants in symptomatic heart failure (NYHA II-IV) with an ejection fraction of 35% or less. They were all in sinus rhythm with a pulse rate of at least 70 beats per minute. Participants were on stable background treatment which included a beta-blocker, if tolerated. Treatment was randomly assigned to ivabradine titrated to a maximum of 7·5 mg twice daily or matching placebo.
The primary outcome of the study was a composite of cardiovascular death or hospital admission for worsening heart failure. Mean follow up was 22.9 months.
793/3,241 (24%) patients in the ivabradine group and 937/3,264 (29%) of those taking placebo had a primary endpoint event (HR 0·82, 95% CI 0·75-0·90, p<0·0001, NNT ~24). The difference was mainly driven by a reductions in the rate of hospital admission for heart failure (21% with placebo versus 16% with ivabradine, HR 0·74, 0·66-0·83; p<0·0001, NNT ~21) and death due to heart failure (5% with placebo versus 3% with ivabradine, HR 0·74, 0·58-0·94, p=0·014, NNT ~88). A greater number of patients treated with ivabradine reported bradycardia (5% versus 1%) and visual disturbances (3% versus 1%).
The authors of the study conclude that, "our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure ". However, an editorial in the same issue of the Lancet and the British Heart Foundation both call for further research to assess the place in therapy for ivabradine.
It should be noted that ivabradine is not currently licensed for use in heart failure and that at the current cost of £39.00 for 28 days of treatment it would cost approximately £84,000 to treat 88 patient in order to prevent one death due to heart failure.
Action: Clinicians should be aware of this study. Pending additional research it would be wise to use the recently updated the Heart Failure Clinical Guideline produced by the National Institute for Health and Clinical Excellence.