Ezetimibe to Help Lower LDL-C



Alan Brown, MD: Let’s talk about some of the newer therapies, because that’s also going to be very important to our audience. We have a couple of new therapies and some that aren’t so new but are newer than statins by a long shot. Let’s start with something that’s not so new. We’ll have just a few comments, so we can get to the newer stuff, like ezetimibe.

It shocks me that a lot of folks, even a lot of cardiologists, still hold the myth that ezetimibe doesn’t reduce cardiovascular events. They heard that from some of our colleagues for many years, and they’re unaware of the IMPROVE-IT data. Pam, do you want to start by telling us about ezetimibe? Whom should we use it in? How does it compare to doubling the dose of a statin? What do the outcome data look like?

Pamela Bowe Morris, MD: That’s a lot of information all in 1 bite. Ezetimibe is an extremely useful tool. Importantly, there’s some variability, so we return to the concept of normal. What is the mean or median response to ezetimibe? It’s somewhere in the range of 15% to 20%, maybe 25%, reduction in LDL [low-density lipoprotein] cholesterol. I carry around in my head about 20%. Having said that, there is remarkable inter-individual variability, in terms of response. I’ve had some people have a very robust reduction in LDL cholesterol. In a patient who needs additional LDL lowering, it’s a great tool.

I typically prefer to use maximally tolerated statin therapy before incorporating ezetimibe. It is true that doubling the statin dose gives you the rule of 6 or 7, depending on which rule you quote, in terms of reduction of cholesterol. But we do have really good evidence that higher-intensity statin therapy is of greater benefit than lower-intensity statin therapy. That tends to be my first go-to before adding a nonstatin. In patients who have a contraindication to higher-intensity statin therapy or have had adverse effects, I go to a nonstatin therapy more quickly.

It is oral and it’s inexpensive. When I give patients the pros and cons of not going to ezetimibe, or maybe jumping to an injectable therapy, most say they’d like to give the oral therapy a try, and we do it. Some insurance companies require it before you can move to an injectable therapy. In any event, it’s a great tool.

Alan Brown, MD: Yes. That’s why the guidelines have said to step through ezetimibe because of the variability in response. When it was expensive, everyone said it was useless. The minute it went generic, it’s the best thing since milk and butter. There are outcome data. We have the IMPROVE-IT data, which showed modest LDL lowering, yet the data do show outcomes. Keith, you wanted to say something.

Keith C. Ferdinand, MD: Yes. Ezetimibe is a good drug. It does help patients. We talked about earlier statin intolerance. If they can’t tolerate the higher-intensity statin, they can still use the statin and get some of the benefits. I agree with Pam that the higher-intensity statin has the more robust data. There’s a study out of Japan called EUTOPIA, with patients over 75 years old. There were more than 3900 patients enrolled, and they appeared to have a decrease in cardiovascular events with ezetimibe. LDL lowering, if done safely and effectively, appears to be a nice surrogate for decrease in cardiovascular events. It doesn’t appear to have a lot of off-target adverse effects, so I still use a lot of ezetimibe.

Alan Brown, MD: It’s like tripling the dose of the statin when you add ezetimibe. Pam pointed out the rule of 6. Every time you double the dose, you get another 6% lowering. If you add ezetimibe, you’re going to get 17% to 20%. I would have been much happier with IMPROVE-IT if it used 10 mg of atorvastatin plus 10 mg of ezetimibe vs 80 mg of atorvastatin. That would have given us some real information on whether a combination therapy gives you the same outcomes and if it achieves the same LDL. We don’t have those data. We only have high-dose vs low-dose statin data, as Pam pointed out.

I agree with Keith that this is important for a lot of patients who are either scared of or can’t tolerate high doses. Seth, and then Matt?

Seth J. Baum, MD: We’re all agreeing about everything, so I figured I’d bring up something that’s a little provocative and controversial. I understand the guidelines. I’m going against the guidelines to some degree by starting with a low-dose statin. I will do that particularly in a patient who is prediabetic, is obese, and may be afraid of becoming diabetic on a high-dose statin. I would start with a low-dose, high-intensity statin like rosuvastatin 10 mg, and add ezetimibe. I get the same LDL reduction that I would have gotten, with perhaps a mitigated risk of the diabetes or other adverse effects from the statin.

We have enough evidence that it’s the LDL that matters. We even have studies showing that we drop LDL on the basis of diet alone, and it’s the LDL achieved that matters. We have enough evidence that it’s all about the LDL. It’s all about the LDL, stupid. It’s all about the LDL, and I feel very comfortable doing that in my shared decision-making experience with my patients.

Alan Brown, MD: Matt, do you have anything to add?

Matthew J. Budoff, MD: No. I do almost the opposite of Seth. I try to push the statin, and then if I can’t get to goal, I add ezetimibe. But I still believe that the maximally tolerated statin dose is going to give us more bang for our buck than low-dose statin plus ezetimibe. We don’t have a trial to prove that either way, so we can each take our own approach to what we do. If they tolerate 80 mg of atorvastatin and they get to goal, I’m much happier than if they’re taking 2 pills and on 10 mg of atorvastatin and 10 mg of ezetimibe. I’d rather them be on 1 pill and 1 high-dose statin if they can tolerate it. If they don’t tolerate it, I’ll do what everyone else does.

Transcript Edited for Clarity

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