ESC Congress 2010: SHIFT study

[Pyankov Vasily]

SHIFT: Effects of ivabradine on cardiovascular events in patients with moderate to severe chronic heart failure and left ventricular systolic dysfunction

Background: Chronic heart failure (HF) is associated with high mortality and morbidity. Elevated resting heart rate is a risk factor for adverse outcomes. We hypothesized that reduction of heart rate by the selective sinus node inhibitor ivabradine could improve outcomes in HF.

Methods: In this randomized, double-blind, placebo-controlled multinational study, patients were eligible if they had symptomatic HF and left ventricular ejection fraction ≤35%, were in sinus rhythm with heart rate >=70 bpm, had a hospitalization for HF within the previous 12 months and were on stable background therapy including a beta-blocker when tolerated. Overall, 6505 patients were randomly assigned to ivabradine (N=3241) titrated maximally to 7.5 mg twice daily or matching placebo (N=3264). The primary endpoint was the composite of cardiovascular death or hospital admission for worsening HF.

Findings: Median follow-up was 22.9 months. In total, 793 (24.5%) patients in the ivabradine group and 937 (28.7%) patients in the placebo group had a primary endpoint (HR, 0.82, 95% CI 0.75–0.9, p<0.0001). The effects were driven mainly by hospital admissions for worsening HF, which were reduced from 20.6% to 15.9% (HR, 0.74, 95% CI 0.66–0.83, p<0.0001) and deaths due to HF (HR, 0.74, 95% CI 0.58–0.94, p=0.014). There were fewer cardiovascular deaths (HR, 0.91, 95% CI 0.80–1.03) and all-cause deaths (HR, 0.90, 95% CI 0.80–1.02) in the ivabradine group. Ivabradine reduced all-cause hospital admissions (HR, 0.89, 95% CI 0.82–0.96, p=0.003) and was well-tolerated. The findings were consistent across several prespecified subgroups, though patients who had relatively high heart rate had the greatest reductions in the primary endpoint with ivabradine.

Interpretation: Our results support the importance of achieving heart rate reduction with ivabradine to improve clinical outcomes in HF and confirm the important role of heart rate in the pathophysiology of HF.

http://www.escardio.org/congresses/esc- ... t=dontmiss