COMMENTARY

Ivabradine/Corlanor: Europe vs US Differences

Ileana L. Piña, MD, MPH

Disclosures

August 19, 2015

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Ivabradine: A New Drug for Heart Failure

Hello. This is Ileana Piña. I'm the associate chief of cardiology at Montefiore Einstein Medical Center and the Albert Einstein College of Medicine in the Bronx, New York, and this is my blog.

In other blogs I have talked to you about some of the newer agents that are on the horizon for heart failure. It has been many, many years since we have had a brand-new drug on the market for which we can say, "Wow, this is dedicated to the heart failure population." However, now the planets are aligning and we have at least two or three drugs on the horizon. One is actually approved and that's ivabradine.

Ivabradine in the United States has been marketed as Corlanor® by the company Amgen. The marketing strategies have already come out and are very, very obvious. It's interesting because this drug is approved in Europe, and having just come from the ESC Heart Failure meetings, there is a tremendous amount of enthusiasm for the drug.

SHIFT: A European Trial

The labeling is different. The labeling here in the United States is for heart rates over 70 bpm where you have not been able to get the heart rate down with medical therapy. It's for prevention of hospitalizations, not for mortality. However, the approval in Europe is for mortality, and so the excitement in Europe around this drug may actually be higher than here in the States.

So, when are we going to use this drug? Let me remind the audience that the trial that brought it to market in Europe was called SHIFT.[1] SHIFT was done totally in European patients. There were no North American or US patients, and therefore no African Americans. We have learned that there are some drugs that do much better in African Americans and some that don't do so well, so we feel that this population is critical.

Adequate Beta-Blocker Dosing

If we examine the SHIFT trial closely, many patients were not on adequate beta-blocker therapy or at target. So before you think of using this drug, go back and read the guideline recommendations for beta-blocker dosing. Toprol-XL®, or metoprolol succinate, which is the long-acting metoprolol, has a target of 200. Bisoprolol, which is widely used in Europe and a very good beta-blocker, well tested in the CIBIS-II trial,[2] is hardly used here in the States and the doses are 5 mg or up to 10 mg daily. Then there is carvedilol (Coreg®), which is now very inexpensive in the United States; you can sometimes get a 2-week supply for $4. The target for heavy people (over 85 kg) is 50 mg twice daily, and for patients who are less than 85 kg, it's 25 mg twice daily. With these doses, most of the time the heart rates will fall, at the very least to 70 bpm. That's the number where the approval process takes place.

So, do we get these heart rates down? Well, we have to look at large databases to see whether we actually do it. In my own HF-ACTION trial[3] (the National Heart, Lung, and Blood Institute exercise trial), in patients who have heart failure with reduced ejection fraction or ejection fractions less than 35%, our baseline heart rate was 70 bpm. And our use of beta-blockade was 95% with a mean carvedilol dose of 37 mg. I think that we can do it. Let's try to do it before we add one more drug.

I believe that the drug is very well tolerated, which may be the reason that the FDA approved it, because the side-effect profile is very, very good. However, in patients in whom you definitely can't beta-block or who don't tolerate the higher levels, you may want to consider adding ivabradine to those patients to get their heart rates lower and potentially improve [frequency of] hospitalizations.

Ileana Piña, singing off.

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