Paradigm Shifts in Lipid Lowering - Episode 12
Norman Lepor, MD, FACC, FAHA, FSCAI, challenges the use of ezetimibe before a PCSK9 inhibitor in a population with no acute coronary syndrome.
Norman Lepor, MD, FACC, FAHA, FSCAI: Do we really think we should start ezetimibe before we go to a PCSK9 inhibitor? I sort of don’t, and I think the reason is we don’t have a lot of data with ezetimibe in a non-ACS [acute coronary syndrome] patient population. Look at the IMPROVE-IT trial. It took 7½ years to get a 6%-plus reduction of events. I agree, lower is better with LDL [low-density lipoprotein], and certainly it does have some modest effect, but do we really feel that we have to add another layer?
Keith C. Ferdinand, MD: Well, I like the fact that Dean backed us up to high-intensity statins, because we’re going to talk more about statins in the next segment. We don’t want to forget statins first, second, and third. But if you look at the PCSK9 outcomes trials, only 3%, 4% of the patients were on ezetimibe. Then the guidelines say start with ezetimibe and if needed, PSCK9 inhibitors, but that didn’t really reflect the outcome studies. Did anyone else see that as a problem? I think when we’re using a cost-effective model, it changed the next day because there was a 60% reduction in the cost of the PCSK9 inhibitor.
Manesh Patel, MD: I think as, Keith, you’ve highlighted, some of the guidelines, and this is something that’s happening in all of our clinical practices. They’ve gone beyond just the evidence and are thinking a bit about access and cost, too. Because I think if you had your druthers, and had the opportunity, you would certainly say that it’s reasonable to go to a PCSK9 for secondary prevention if somebody is not at target goal after high-intensity statin, as has been studied in the 2 outcomes studies, secondary prevention for PCSK9 inhibition, and as you highlighted, low usage of ezetimibe.
I think part of that thought process is that it’s likely related to getting access. And to answer your Lp(a) [lipoprotein(a)] question, it’s a little like the conversation we had about triglycerides. We have known for a long time that Lp(a) is a risk factor for cardiovascular events. We have not had things that have lowered it, and so we have always been looking for that. I’m excited that PCSK9 inhibition, whether it’s through a monoclonal antibody or inclisiran, reduces it some, and that is probably part of the pleiotropic meaningful effects of what’s going on.
We also know that other agents are coming down the pipe that are going to be very specifically directed at Lp(a), and we’ll find out with those studies if that actually improves outcomes.
Dean Karalis, MD: Two points quickly, getting back to what Norm said. I think you do get more bang for your buck with a PCSK9 inhibitor. The issue is getting it through the payers and the approval if you haven’t first tried ezetimibe.
But one of the other things, and I think it’s important for any listeners, is that if a patient is denied or can’t afford a PCSK9 inhibitor, I see patients who are referred to me where ezetimibe is not even thought of as another option for patients who can’t afford or are denied a PCSK9 inhibitor. And it is effective, it’s safe, it’s tolerable. And in Philadelphia, you can get a 90-day supply for about $10.
We underutilize ezetimibe, not only in high-risk patients, but also in primary prevention patients who are statin intolerant or who can’t tolerate the appropriate guideline-based dose of a statin.
Keith C. Ferdinand, MD: Yes, I think you are right. The cost effectiveness of this comes into play. I was just mentioning that the outcomes trials had a low use of ezetimibe. Then the guidelines, they didn’t mandate it, but suggested that be the second step, when it really didn’t reflect what was seen in the outcomes trials with alirocumab and evolocumab. That was my concern.
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Transcript Edited for Clarity