Efficacy and safety of ivabradine in chronic heart failure across the age spectrum: insights from the SHIFT study

Abstract

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. 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. 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.