Bohm M, et al. Clin Res Cardiol. 2013 Jan;102(1):11-22.
The If inhibitor Ivabradine consequently decreased major cardiovascular outcomes with heart rate reduction in HF patients in sinus rhythm with heart rate ≥70 bpm in SHIFT. In the detailed analysis of heart rate exhibited that, with beginning from a resting heart rate of 70 bpm, improving 5-bpm heart rate accessions progressively elevated 16% risk for cardiovascular death or HF hospital admissions. A group of heart failure patients in whom the drug is labelled now, no data are available. Thus, Bohm M, et al. conducted a study to execute an in-depth analysis on effects in patients at heart rates ≥75 bpm.
SHIFT was a randomised double-blind, placebo-controlled, parallel-group clinical trial. Patients with moderate to severe HF and systolic dysfunction with LVEF ≤35 % in sinus rhythm with heart rates ≥70 bpm were included. Patients were randomly allocated to Ivabradine or placebo treatment. 5 mg of Ivabradine twice daily was given initially. Study drug was uptitrated to a target dose of 7.5 mg twice daily (or matching placebo) during 28 days until the resting heart rate was ≤60 bpm or there were signs and symptoms of bradycardia. The effects in patients with heart rates ≥75 and <75 bpm were analysed. The median follow-up was 22.5 months in the population ≥75 bpm and 23.4 months in the subgroup <75 bpm.
Ivabradine induced a significant reduction in primary outcome by 24% as compared to placebo in the ≥75 bpm group (HR 0.76, 95 % CI, 0.68–0.85, p <0.0001). (Figure 1)
Figure 1: Kaplan–Meier cumulative event curves on Ivabradine or placebo for the primary composite endpoint in the ≥75 bpm group
Ivabradine exhibited 17% reduction in cardiovascular and all-cause mortality (p= 0.0166 and p= 0.0109, resp), 39% reduction in death from HF (p = 0.0006), 18% reduction in all-cause hospital admissions (p <0.0001) and 21% reduction in any cardiovascular hospital admissions (p <0.0001) in the ≥75 bpm group.
Ivabradine showed significant reduction in hospital admissions for HF by 30% in the ≥75 bpm group (HR, 0.70, 95 % CI, 0.61–0.80), p <0.0001). (Figure 2)
Figure 2: Kaplan–Meier cumulative event curves on Ivabradine or placebo for hospital admission for worsening of heart failure in the ≥75 bpm group
It was concluded that Ivabradine showed greater effects on outcomes with accomplishment of heart rates <60 bpm or decrease in heart rate of >10 bpm anticipated best risk reduction in patients with heart rate ≥75 bpm.
SHIFT: Systolic heart failure treatment with the If inhibitor Ivabradine trial; LVEF: left ventricular ejection fraction
