Efficacy and Safety of Ivabradine in Chronic Heart Failure Across the Age Spectrum: Insights from the SHIFT Study

AIMS: To test whether the efficacy and safety of the selective heart rate-reducing agent ivabradine changes according to age in chronic heart failure (HF) patients. METHODS AND RESULTS: The ivabradine and placebo arms of SHIFT, which enrolled 6505 chronic HF patients, were combined and age distribution was divided by quartiles to give four groups (<53 years, n = 1522; 53 to <60 years, n = 1521; 60 to <69 years, n = 1750; and ≥69 years, n = 1712). The effects of ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group. A subgroup (602 patients) underwent 24 h ambulatory ECG Holter monitoring. The relative risk of the primary endpoint (cardiovascular death or hospitalization for worsening HF) was reduced by ivabradine in all age groups, ranging from 38% hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.50-0.78, P < 0.001 in the youngest patients <53 years to 16% (HR 0.84, 95% CI 0.71-0.99, P = 0.035) in the oldest patients ≥69 years. Ivabradine up-titration reduced heart rate similarly in all age groups, by 11 b.p.m. As anticipated, bradycardia and phosphenes occurred more frequently with ivabradine, at a similar rate whatever the age. In the Holter substudy, there were no episodes of severe bradycardia and no clinically relevant pauses with ivabradine in any age group. CONCLUSIONS: Age does not limit the appropriate use of ivabradine in patients with chronic HF and systolic dysfunction. The safety and efficacy of ivabradine are comparable across all age groups.