Ivabradine—a paradigm SHIFT in heart failure?

A raised resting heart rate is a known risk factor for adverse outcomes in patients with chronic heart failure. In addition, the benefit of many drugs for heart failure appear to be at least in part caused by their ability to lower the heart rate, perhaps thereby attenuating the effect of energy starvation of the myocardium. The aim of the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) was to assess the effect of heart rate reduction by ivabradine, a selective sinus-node inhibitor.

Patients with symptomatic heart failure and a left ventricular ejection fraction of 70 bpm. In addition, all patients had been admitted to hospital for heart failure in the previous year, and were receiving stable background treatment including a β blocker (where tolerated). In total 6558 patients were randomly assigned to either to ivabradine up to a maximum of 7.5 mg twice daily, or matching placebo. The primary end point was the composite of cardiovascular death or hospital admission for worsening heart failure.

The median follow-up was 22.9 months, and over this period 793 patients in the ivabradine group and 937 patients in the placebo group had a primary end-point event (24% vs 29%; p<0.0001). This was driven by fewer admissions for heart failure (16% vs 21%, p70 bpm, the use of ivabradine was associated with a reduction in heart failure hospital admissions and deaths.

▶ Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376:875–85.

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