Ivabradine for Inappropriate Sinus Tachycardia

Inappropriate sinus tachycardia (IST) is a condition characterized by an abnormally rapid heart rate (tachycardia), both at rest and during exertion, which usually affects younger people who are otherwise completely healthy. Those who suffer from IST commonly experience severe palpitations as well as exercise intolerance and fatigue, and the condition can be quite disabling. The effective treatment of IST, unfortunately, is often challenging.

Ivabradine is a relatively new drug marketed for the treatment of angina and heart failure. In recent years ivabradine has shown significant promise for the treatment of IST. Reports indicate that it might also be effective for other dysautonomia syndromes in which tachycardia is often a prominent feature.

Ivabradine was originally developed for treating angina and was approved for use in much of the world in 2005. It was approved in the U.S. in April 2015 for the treatment of heart failure, but not for IST.

Several small reports — often describing one or two patients — began appearing soon after the drug came into clinical use, suggesting that ivabradine might be useful in treating patients with IST. Then, in 2012, a well-designed randomized, placebo-controlled clinical trial was reported in Italy, which concluded that ivabradine may indeed be uniquely effective for this condition. IST patients randomized to ivabradine showed an overall 75% reduction in symptoms, and 50% of treated patients reported the immediate and complete resolution of symptoms. Side effects were minimal. Compared to what is typically seen with other medical treatments used for IST, such a result is indeed striking.

A more recent non-randomized trial with ivabradine in 24 patients with IST showed similar favorable outcomes. In this trial, however, the drug was stopped in 10 patients after one year to see what would happen (the other patients refused to stop taking the drug), and 8 of these 10 these patients had no recurrence of IST.

Postural orthostatic tachycardia syndrome (POTS) and vasovagal syncope are two other dysautonomia syndromes in which sinus node tachycardia often plays a prominent role in producing symptoms. So it is not surprising that doctors would choose to try ivabradine in these conditions.

There is little actual data on the use of ivabradine for POTS, but doctors around the world have used the drug in selected individuals with this condition. The data that does exist, however, suggests that, at least in some people, controlling the tachycardia with ivabradine can reduce or eliminate the other symptoms associated with POTS. A randomized clinical trial using ivabradine for POTS is now being conducted in Israel.

While vasovagal syncope is associated with a precipitous drop in blood pressure and (usually) in heart rate, it is well known that prior to the loss of consciousness (that is, during the “warning symptoms” people often experience with this condition), an abnormally rapid heart rate is often present. In a pilot study of 25 patients with vasovagal syncope who demonstrated such a tachycardia just prior to passing out, over 70% had favorable results with ivabradine — either a significant reduction or elimination of symptoms.

So, ivabradine shows real promise for all the dysautonomias in which sinus tachycardia is a major feature.

While this drug has been used for over a decade in Europe, in much of Asia, and in Russia, Australia, and Canada, it was approved in the U.S. only in April 2015. Furthermore, the only approved indication for ivabradine in the U.S. Is for the treatment of heart failure. (Ivabradine is marketed by Amgen, under the trade name Corlentor.)

If you live in the U.S. and have IST (or one of the other dysautonomias that may respond to this drug), and if your doctor believes that ivabradine may be beneficial to you, he or she is now able to prescribe it. However, since ivabradine is only labeled for heart failure in the U.S., your doctor must be willing to prescribe it for "off-label" use. In any case, ivabradine is now a realistic option even for Americans who have IST.

Ivabradine blocks the If channel, a channel in cell membranes that allows sodium and potassium to enter cells. The If channel (the “f” stands for “funny,” so-named because this channel behaves differently than most other channels), plays a major role in firing the sinus node, which regulates the normal heart rhythm. By blocking the If channel, ivabradine slows the rate of firing of the sinus node, and thus slows the heart rate. This mechanism of slowing the sinus heart rate is fundamentally different from the mechanisms employed by beta-blockers and calcium channel blockers, so ivabradine often produces slowing of the heart rate even when these other drugs fail to do so.

The only prominent side effect reported with ivabradine, seen in around 15% of patients, is a visual condition called the “luminous phenomenon.” This phenomenon is described as experiencing an abnormal “brightness” in the visual fields, without any change in visual acuity. It is thought to result from blocking a channel in retinal cells that is similar to the IF channel in the heart. Fortunately, this side effect is usually mild and most often resolves on its own. One recent report suggests that patients on this drug may have an increased risk of atrial fibrillation. Other less common side effects include a headache and dizziness. Overall the drug reportedly is quite well tolerated.