August 11, 2026The Lancet2,575 citationsOpen Access
Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study
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Key Result
Ivabradine significantly reduced the composite of cardiovascular death or hospital admission for worsening heart failure compared with placebo (24% vs 29%; HR 0.82; 95% CI 0.75-0.90; p<0.0001).
Key Points
- To assess the effect of ivabradine in reducing heart rate on clinical outcomes in patients with chronic heart failure.
- Randomized, double-blind, placebo-controlled, parallel-group study
- Included symptomatic heart failure patients with ejection fraction ≤ 35% and heart rate ≥ 70 bpm
- Primary endpoint was a composite of cardiovascular death or hospital admission for worsening heart failure
- 24% of patients on ivabradine had events vs 29% on placebo (HR 0.82, 95% CI 0.75-0.90, p<0.0001)
- 21% hospital admissions for heart failure in placebo vs 16% in ivabradine (HR 0.74, 0.66-0.83; p<0.0001)
- 5% ivabradine patients experienced bradycardia vs 1% placebo (p<0.0001)
Study Design
Type
RCT (n=6,558)
Blinding
Double-blind
Randomization
computer-generated allocation schedule
Structured PICO
Does ivabradine reduce the composite of cardiovascular death or hospital admission for worsening heart failure in patients with symptomatic heart failure, LVEF ≤35%, and resting heart rate ≥70 bpm?
P
Population
6,558 patients with symptomatic heart failure, LVEF ≤35%, and resting heart rate ≥70 bpm, followed for a median of 22.9 months.
I
Intervention
Ivabradine titrated to a maximum of 7.5 mg twice daily
C
Comparator
Matching placebo
O
Outcome
Composite of cardiovascular death or hospital admission for worsening heart failurecomposite
In patients with symptomatic heart failure, LVEF ≤35%, and resting heart rate ≥70 bpm, ivabradine significantly reduces the composite of cardiovascular death or heart failure hospitalization.
Main Result
Hazard Ratio: 0.82 (95% CI 0.75–0.9)
Absolute Event Rate: 24% vs 29%
p-value: p=<0.0001
Abstract
BACKGROUND: Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure. METHODS: Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960. FINDINGS: 6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 21% placebo vs 514 16% ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151 5% vs 113 3%; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0.0001). INTERPRETATION: Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder. FUNDING: Servier, France.