Ivabradine reduces mortality and hospitalizations in chronic heart failure. The SHIFT Study Commentary

Abstract

Over last decade high mortality and morbidity in chronic heart failure (CHF) is still observed. Observational data suggest that raised resting heart rate is a predictor of adverse outcome in CHF. SHIFT was international, randomized, double-blinded study designed to assess the effect of heart-rate reduction by adding to standard therapy selective sinus-node inhibitor ivabradine on outcomes in heart failure. The inclusion criteria for participation in this study were: symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, sinus rhythm with heart rate ≥70 bpm, admission to hospital for heart failure within the previous year, and stable background treatment including β-blocker. Patients were assigned to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. 24% patients in the ivabradine group and 29% in placebo group had a primary endpoint event (p <0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (p <0.0001) and deaths due to heart failure (151 [5%] vs 113 [3%]; HR 0.74; 0.58–0.94, p=0.014). Treatment with ivabradine was associated with higher frequency of symptomatic bradycardia ( 5% vs 1%; p <0.0001). Results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure.