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Use of ivabradine in heart failure with reduced ejection fraction

Wilson S Colucci, MD
Section Editor
Stephen S Gottlieb, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


The selective sinus node inhibitor ivabradine reduces the risk of hospital admission for heart failure (HF) and death from HF in patients with HF with reduced ejection fraction (HFrEF) [1]. This benefit is associated with reduced sinus rate.

The use of ivabradine in the treatment of HFrEF is discussed here. An overview of therapy of HFrEF and the pharmacologic therapy of HFrEF are presented separately. (See "Overview of the therapy of heart failure with reduced ejection fraction" and "Pharmacologic therapy of heart failure with reduced ejection fraction".)


Heart rate as a therapeutic target — Heart rate reduction is a potential therapeutic target in patients with heart failure with reduced ejection fraction (HFrEF) since an elevated heart rate is associated with worse cardiovascular outcomes. An elevated heart rate reflects, in part, activation of the sympathetic nervous system and withdrawal of parasympathetic activity, which are components of the neurohumoral response to HF [2]. An elevated plasma norepinephrine concentration is a marker for poor survival in these patients [3]. It has been unclear whether heart rate is a determinant of prognosis, or simply a marker for increased sympathetic tone. While the relative contributions of increased heart rate versus the underlying neurohumoral abnormalities are difficult to determine, the beneficial effects of ivabradine, an agent that acts solely by decreasing heart rate (discussed below), suggests that an elevated heart rate, per se, contributes to adverse outcomes in patients with HFrEF. Possible detrimental effects of elevated heart rate include heart rate-related increases in myocardial oxygen consumption and shear stress and decreases in myocardial perfusion [4]. (See "Predictors of survival in heart failure with reduced ejection fraction", section on 'Neurohumoral activation and heart rate'.)

Heart rate lowering drugs have differing effects on heart failure — While some heart rate lowering drugs are beneficial in patients with HFrEF, various types of heart rate lowering drugs have differing mechanisms of action, as well as differing effects on outcomes in patients with HFrEF.

Beta blockers and ivabradine both decrease heart rate and improve clinical outcomes in patients with HFrEF, but they have different mechanisms of action as discussed below. For both drugs, there is evidence that clinical benefit is related to heart rate lowering, although beta blockers likely have other beneficial effects. (See "Use of beta blockers in heart failure with reduced ejection fraction".)

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Literature review current through: Nov 2017. | This topic last updated: Jun 28, 2016.
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