Using Apheresis in Lowering Lp(a)



Joyce L. Ross, CRNP: I have a couple of things I want to touch on that are important to talk about. In our world of familial hypercholesterolemia [FH] we started the first commercial use of LDL [low-density lipoprotein] apheresis at the University of Pennsylvania back in 1996. At that time, we didn’t have all the wonderful medications that we have today, and we had people who were having second, third, and fourth vascular events and indeed some dying because we couldn’t get their cholesterol to a level that they weren’t progressing on and on.

Back in 1996 it was so difficult to get insurance companies to understand what apheresis is. It’s very similar to what we’ve gone through with PCSK9 inhibitors. I think, “Don’t worry, it will pass because it’s about education.” What we had to do for some patients, and particularly a patient with homozygous familial hypercholesterolemia, we have to remove the cholesterol manually from the blood. This is something that has to happen every week or every 2 weeks for the patient for the remainder of their life or, as I used to say, “until we find something better that works for you.” It’s taken through a column and the LDL [low-density lipoprotein] cholesterol through a system is taken into a filter, and what’s interesting, it takes all the Lp(a) [lipoprotein (a)] out too, so it creates another big problem.

We actually have patients who were treated whose LDL was OK, but we also had a problem because they had very high Lp(a). So they would close off their stents, and they would have other problems even with good LDL cholesterol. We know that there were other things and there still are things that we need to do in certain patient populations to manage this. But the problem with apheresis is that there aren’t many centers available across the country at which we can do this. It’s important we understand it’s out there, and it’s there for the right patient at the right time. So many patients have been able to get off of this. It’s exciting, but you have to explain to people, if you don’t have those receptors and get back to that word that you brought up, that’s so critical. We know that the statin upregulates the receptor. What is a receptor? It’s a door. It’s the way the cholesterol is supposed to get back to your liver so it can be gotten rid of in a normal fashion.

When I think about PCSK9 inhibitors, I think we should have a motto, “save the receptors.” You can use them over and over again, and that’s what makes it such a valuable source of medication for our patient population. We’re not just doing something, we’re treating the disease or that disorder, that receptor that they may not have enough of, or the receptors that don’t work.

Lynne Braun, PhD, CNP: Joyce, thank you for that wonderful description of LDL apheresis. As you know, I don’t have that much experience in using LDL apheresis, so I’m glad that you talked about that. You mentioned that LDL apheresis also lowers lipoprotein (a) levels. Is that an indication at this point?

Joyce L. Ross, CRNP: It is. It is a brand-new indication that the FDA has now granted for removal of Lp(a) in patients in which they tried other modalities. Of course, you’re going to go to all the other things first. To date, we don’t have a treatment to get rid of Lp(a).

Lynne Braun, PhD, CNP: Correct.

Joyce L. Ross, CRNP: We don’t even know if by getting rid of it, it changes. But I can tell you that from clinical practice, in patients back in 1996, 1997 who were doing fine for their LDL cholesterol, they had this high Lp(a) that caused them to come back for unstable angina, for stent replacement, for all kinds of things. When we treated, of course it was not within the guideline, but Daniel J. Rader, MD, with whom I had had the privilege of working with for so many years, felt that if we did something mechanical, perhaps we could change it, and we did. So those pieces of information back that long were finally put together in the work of Patrick M. Moriarty, MD, out in his area where they have a ton of FH, and others. Through the National Lipid Association and American Heart Association [AHA], and all others who got this data together, they said, “This is important.” So, yes, it is something that can be useful in a patient who has an LDL that they’re doing well with, but not with Lp(a). But, it doesn’t mean you don’t take the other medications.

Lynne Braun, PhD, CNP: Right, exactly.

Joyce L. Ross, CRNP: But I think apheresis has got its time and its place, and it’s got its patients.

Lynne Braun, PhD, CNP: Before you go on, I want to talk about 2 more things with elevated Lp(a).

Joyce L. Ross, CRNP: Go ahead.

Lynne Braun, PhD, CNP: First of all, PCSK9 inhibitors lower Lp(a), but unfortunately, it’s not an indication. We can’t get that approved, but perhaps sometimes patients have other indications for PCSK9 inhibitors. They also happen to have an elevated Lp(a), so by placing them on that agent, that will lower their Lp(a), obviously. The other thing I wanted to mention is in the AHA/ACC [American College of Cardiology] guideline, elevated Lp(a) is considered a risk-enhancing factor, so that’s important. The European guidelines were published about 9 months after the American guidelines. In the European guidelines, measuring lipoprotein (a) in individuals who are at increased risk because they have a positive family history or they have disease, that is a recommendation, that Lp(a) is measured at least once.

Joyce L. Ross, CRNP: That’s critically important because as I would explain to a patient who has known cardiovascular disease, we go ahead and test apolipoprotein B and Lp(a) just to find other reasons why that happened to them, and have a fully covered treatment protocol. What’s also important is if you had that same dad I was talking about who had FH and had a high Lp(a), if he has 4 children, it is likely that 2 of those children have it as well. So I talk about it as being that chance to go back and work with people very early on who are high risk. You mentioned those risk-enhancing factors, and you mentioned all these things that we know today are so important to talk about.

Transcript Edited for Clarity

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