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)

Eur J Heart Fail. 2010 Jan;12(1):75-81. doi: 10.1093/eurjhf/hfp154. Epub 2009 Nov 5.


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 < or =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 > or =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 > or =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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Anti-Arrhythmia Agents / therapeutic use*
  • Benzazepines / therapeutic use*
  • Chronic Disease
  • Clinical Protocols
  • Data Collection
  • Double-Blind Method
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Ivabradine
  • Male


  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Benzazepines
  • Ivabradine