Rationale and design of a randomized, double‐blind, placebo‐controlled outcome trial of ivabradine in chronic heart failure: the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT)

Aims Elevated heart rate is a significant marker for mortality and morbidity in cardiovascular disease including heart failure. Despite background treatment with a beta‐blocker, many patients with heart failure and low ejection fraction maintain a heart rate above 70 b.p.m. Ivabradine reduces heart rate directly through inhibition of the I f ionic current. Methods SHIFT is a randomized, double‐blind study designed to compare ivabradine with placebo on outcomes in patients with symptomatic chronic heart failure (NYHA class II–IV), left‐ventricular ejection fraction ≤35%, and a prior hospitalization for worsening heart failure within the previous 12 months. Randomized treatment is given on top of guidelines‐based therapy for chronic heart failure, including a beta‐blocker at optimized dose. Resting heart rate at baseline must be ≥70 b.p.m. The primary endpoint is the composite of the time to first event of cardiovascular death or hospitalization for worsening heart failure. Secondary endpoints include all‐cause, cardiovascular and heart failure mortality, and hospitalization. The randomized treatment period lasts approximately 12–48 months. The study will include approximately 6500 patients and will continue until ≥1600 primary endpoints have occurred. The first patient was randomized in October 2006, and the study is expected to end in 2010. Conclusion The SHIFT study will assess if a heart rate reduction by direct sinus node inhibition can reduce cardiovascular outcomes in patients with chronic heart failure and left‐ventricular systolic dysfunction.