Ivabradine (Corlanor) for Inappropriate Sinus Tachycardia (IST)

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.

• Read all about IST and its treatment.

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.

• Read about the dysautonomias.

• Read about the heart’s electrical system.

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 from 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.

• Read about POTS.
• Read about vasovagal syncope.

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.