Ivabradine

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Ivabradine (Corlanor, Amgen) is a relatively new drug that reduces the heart rate by slowing the spontaneous discharge of the sinus node. This mechanism of heart rate slowing is fundamentally different from the way beta blockers or calcium blockers slow the heart rate.

Ivabradine has been used to treat heart failure, stable angina, and some of the dysautonomias, in particular, inappropriate sinus tachycardia (IST).

Ivabradine has been in clinical use in much of the world since 2005. It was approved by the U.S. FDA in April, 2015 for the treatment of heart failure.

How Does Ivabradine Work?

Ivabradine works on the cells of the sinus node by blocking the If channel, a channel in cell membranes that allows sodium and potassium to enter cells. (The “f” in If stands for “funny,” because this channel behaves quite a bit differently than other channels.) Blocking the If channel causes substantial slowing in rate at which the sinus node fires, thus slowing the heart rate. Ivabradine is classified as a “selective sinus node inhibitor.”

What Is Ivabradine Used For?

Heart Failure. While an elevated heart rate has long been known as a common sign of heart failure, the idea of slowing the heart rate as a specific treatment for heart failure is new. Recently, however, results from the SHIFT trial found that heart failure patients treated with ivabradine had improved clinical outcomes.

(The FDA relied on the SHIFT results in issuing its approval of ivabradine.) However, experts are still working out the question of when ivabradine ought to be used in treating heart failure.

Angina. In Europe, ivabradine has been used to treat patients with stable angina.

The rationale for using this drug for angina is: a) increased heart rates are associated with worse outcomes in patients with angina, and b) beta blockers, which also slow the heart rate, have been a mainstay in treating stable angina for decades. However, data from the randomized SIGNIFY trial suggest that, while ivabradine was successful in reducing symptoms of angina, in at least one subgroup of patients the risk of cardiovascular death was increased. The European Medicines Agency subsequently released precautionary recommendations on the use of ivabradine for angina, and the FDA’s approval of ivabradine does NOT include the treatment of angina. At least in the U.S, ivabradine generally is not considered a useful drug for angina.

Inappropriate Sinus Tachycardia. Several small reports, and one randomized trial, strongly suggest that ivabradine can significantly reduce symptoms in at least some patients with IST. Since the treatment of IST is often difficult and frustrating, the recent availability of this drug offers new hope to patients with IST.

What Are the Side Effects of Ivabradine?

The most common side effect of ivabradine is the so-called “luminous phenomenon,” which is described as a sensation of increased, sometimes disturbing, "brightness" in vision. It is experienced in 14% of patients who take ivabradine. Generally the luminous phenomenon is mild, but about 1 in 100 patients cannot take ivabradine because of this side effect.

Other, less common, side effects include bradycardia (a heart rate that is too slow), headache, dizziness, or blurred vision. A recent report suggests that, in patients with heart failure or angina treated with ivabradine, there is an increased risk of atrial fibrillation.

Sources:

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.

Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371:1091.

Calò L, Rebecchi M, Sette A, et al. Efficacy of ivabradine administration in patients affected by inappropriate sinus tachycardia. Heart Rhythm 2010; 7:1318.

Cappato R, Castelvecchio S, Ricci C, et al. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation. J Am Coll Cardiol 2012; 60:1323.

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