Ivabradine for Heart Failure

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In April, 2015, the U.S. Food and Drug Administration approved the new drug ivabradine (Corlanor, Amgen) for the treatment of heart failure. Ivabradine represents a unique approach to heart failure treatment since, for the first time, it targets reduction of the heart rate as a specific target for therapy.

How Does Ivabradine Work?

Ivabradine works by blocking the so-called If channel in the cells of the sinus node, a channel that allows sodium and potassium to transverse the cell membrane.

(The “f” stands for “funny,” because this channel behaves quite a bit differently than other cellular channels.) By blocking the If channel, ivabradine slows the firing of the sinus node, and as a consequence quite reliably lowers the heart rate. Ivabradine is classified as a “selective sinus node inhibitor.”

It is the slowing of the heart rate that provides a therapeutic benefit in some patients with heart failure.

The Effect of Ivabradine in Heart Failure

The reasons investigators thought a selective sinus node inhibitor like ivabradine might be useful in heart failure are: a) the resting heart rate is often faster than normal in patients with heart failure; b) beta blockers , which also reduce the heart rate, are of proven benefit in patients with heart failure; and c) adding ivabradine to a beta blocker can reduce the heart rate even more. The theory that ivabradine could benefit heart failure patients was tested in the SHIFT trial.

In the SHIFT trial, 6558 patients with heart failure and normal sinus rhythm with a resting heart rate above 70 beats per minute while on beta blocker therapy were randomized to receive either ivabradine plus usual heart failure therapy (including beta blockers), or placebo plus usual heart failure therapy.

After an average of 23 months, patients receiving ivabradine had a significant reduction in hospital admissions for heart failure, and a reduced risk of death from heart failure. The overall risk of death, however, was not reduced.

Based on the results of the SHIFT trial, the FDA approved ivabradine in the US for the treatment of heart failure.

Where Does Ivabradine Fit In With Heart Failure?

The results from the SHIFT trial seem robust, as far as they go. However, we should note that this trial only tested ivabradine as a supplement to - and not as a substitute for - beta blockers. In patients with heart failure whose resting heart rates remain relatively high despite optimal beta blocker therapy, adding ivabradine to further reduce the heart rate resulted in significantly improved clinical outcomes.

It bears repeating that the SHIFT trial does not suggest that ivabradine can be used as a substitute for beta blockers. A full dose of beta blockers is required before an assessment can be made as to whether ivabradine might be helpful in a particular patient - that is, whether their resting heart rate in sinus rhythm remains above 70 beats per minute.

Further studies will be required to test whether ivabradine can be safely used as a full or partial substitute for beta blockers.

The really new thing about the SHIFT trial is that it has demonstrated, for the first time, that reducing the heart rate of patients with heart failure is itself a legitimate target of therapy. With this new knowledge, we can expect investigators to look a lot more closely at this and other methods for reducing the heart rate as a treatment for heart failure.


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

Böhm M, Swedberg K, Komajda M, et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 2010; 376:886.

Teerlink JR. Ivabradine in heart failure–no paradigm SHIFT…yet. Lancet 2010; 376:847.

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