You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Identify And Act: Overcoming Barriers to Managing Homozygous Familial Hypercholesterolemia

  • Authors: Marcello Arca, MD; Dirk Blom, MBChB, PhD; Eliot A. Brinton, MD, FAHA, FNLA, FACE
  • CPD Released: 9/7/2022
  • Valid for credit through: 9/26/2023, 11:59 PM EST
Start Activity

Target Audience and Goal Statement

This activity is intended for cardiologists, lipidologists/endocrinologists, nurses, and other HCPs involved in the management of HoFH.

The goal of this activity is that through increased awareness of HoFH, learners will be better able identify patients with HoFH and refer them to specialist centers for treatment.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Appropriate management options for patients with HoFH
  • Have greater competence related to
    • Diagnosis of HoFH
    • Referral to specialist centers for more intensive low density lipoprotein cholesterol (LDL-C) management


WebMD Global requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships with ineligible companies.

Disclosures for additional planners can be found here.


  • Marcello Arca, MD

    Professor of Medicine
    Sapienza University of Rome
    Rome, Italy


    Marcello Arca, MD, has the following relevant financial relationships:
    Consultant or advisor for: Akcea; Alfasigma; Amarin; Amryt; Daiichi Sankyo; Novartis; Pfizer; Sanofi
    Speaker or member of speakers bureau for: Akcea; Alfasigma; Amarin; Amgen; Amryt; Novartis
    Research funding from: Akcea; Amgen; Amryt; Daiichi Sankyo; Novartis; Sanofi
    Contracted researcher for: Pfizer

  • Dirk Blom, MBChB, PhD

    Head of Division of Lipidology
    The University of Cape Town
    Cape Town, South Africa


    Dirk Blom, MBChB, PhD, has the following relevant financial relationships:
    Consultant or advisor for: Amgen; Amryt; Novartis; Sanofi
    Speaker or member of speakers bureau for: Amgen; Amryt; Merck Sharp & Dohme; Novartis; Organon; Sanofi
    Contracted researcher for: Amgen; LIB Therapeutics; Novartis; Sanofi

  • Eliot A. Brinton, MD, FAHA, FNLA, FACE

    Utah Lipid Center​
    Salt Lake City, Utah, United States


    Eliot A. Brinton, MD, FAHA, FNLA, FACE, has the following relevant financial relationships:
    Consultant or advisor for: 89Bio; Amarin; Amgen; Amryt; Dalcor; Esperion; Immunovant; Kowa; Novartis; Pfizer
    Speaker or member of speakers bureau for: Amarin; Amgen; Amryt; Esperion; Novartis
    Research funding from: Regeneron
    Contracted researcher for: Regeneron


  • Ozerk Akgun, MD

    Medical Education Director, WebMD, LLC 


    Ozerk Akgun, MD, has no relevant financial relationships. 

  • Walid Amara, MD

    Medical Education Director, WebMD, LLC 


    Walid Amara, MD, has no relevant financial relationships. 

Compliance Reviewer

  • Susan L. Smith, MN, PhD

    Associate Director, Accreditation and Compliance


    Susan L. Smith, MN, PhD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

Accreditation Statements

    For Physicians

  • The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom (FPM) has reviewed and approved the content of this educational activity and allocated it 0.50 continuing professional development credits (CPD).

    Contact WebMD Global

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information about your eligibility to claim credit, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent participating in the activity. To successfully earn credit, participants must complete the activity online during the credit eligibility period that is noted on the title page.

Follow these steps to claim a credit certificate for completing this activity:

  1. Read the information provided on the title page regarding the target audience, learning objectives, and author disclosures, read and study the activity content and then complete the post-test questions. If you earn a passing score on the post-test and we have determined based on your registration profile that you may be eligible to claim CPD credit for completing this activity, we will issue you a CPD credit certificate.
  2. Once your CPD credit certificate has been issued, you may view and print the certificate from your CME/CE Tracker. CPD credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of the Medscape Education homepage.

We encourage you to complete an Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.


Identify And Act: Overcoming Barriers to Managing Homozygous Familial Hypercholesterolemia

Authors: Marcello Arca, MD; Dirk Blom, MBChB, PhD; Eliot A. Brinton, MD, FAHA, FNLA, FACEFaculty and Disclosures

CPD Released: 9/7/2022

Valid for credit through: 9/26/2023, 11:59 PM EST


Activity Transcript

Marcello Arca, MD: Hello to everyone. I am Marcello Arca. I am Professor of Internal Medicine at Sapienza University of Rome. I would like to introduce my colleagues who will join me today for this program. Professor Dirk Blom, the Head of Division of Lipidology at the University of Cape Town, Cape Town, South Africa, and Professor Eliot Brinton, Past-President of the American Board of Clinical Lipidology, and President of the Utah Lipid Center, Salt Lake City, Utah. And I want to welcome all of you to this Medscape Education program dedicated to homozygous familial hypercholesterolemia (HoFH).

I want just to introduce briefly what is homozygous FH: it is a genetic disorder with lipid metabolism and represents the most severe form of familial hypercholesterolemia. It raises plasma cholesterol, mainly associated with heterogenic lipoprotein called low-density lipoprotein (LDL) to very, very high levels. Despite rare, it has been estimated that homozygous FH affects one in over 250,000 individuals.

It causes accelerated atherosclerotic vascular damage, and without treatment, homozygous FH can lead to ischemic heart disease very early in life, even in childhood. Homozygous FH tends to appear very early in life, so getting diagnosed early is essential to manage the exceptional elevated risk factors in these individuals.

And now I want to say to Dirk: can you explain to the audience why it is so important to start the treatment-- the cholesterol-lowering treatments -- early in life. Moreover, I would like to ask you to show which are the clinical appearance of homozygous FH and which are the alert signs for suspecting this disease in our hypercholesterolemic patient?

Dirk Blom, MBChB, PhD: Thanks very much, Marcello. So, obviously, homozygous FH is the epitome of LDL cholesterol disorders, the LDL is just so high and that is really what drives the pathophysiology in this disorder. I think that most doctors are quite familiar with the concept of pack-years smoked when looking at the damage that smoking causes to your lungs. And in a similar way we can think of cholesterol exposure times years, so if you look at this graph that shows you the cholesterol year burden, then what we have in patients with homozygous FH is a very, very steep trajectory. They rapidly accumulate cholesterol in their arteries and in the rest of their body, till they reach the threshold at which atherosclerotic cardiovascular disease becomes clinically obvious. Now people with average cholesterol and average risk factors may reach this threshold in their 60s or 70s, the heterozygous FH patient in their 40s, or even 30s. But homozygous FH that trajectory is so steep that they can manifest with vascular disease as children or teenagers.

So, our treatment is really focused on bending the curve, just pushing that accumulation of LDL down. So, what we really want to do is we want to lower the LDL as early as possible and as aggressively as possible. And we're going to hear about the options for lowering the LDL cholesterol, but really this is a disorder where there's no time to wait, you have to start treatment.

So very important that we find those patients so that we can treat them early and get them to specialized centers, get them to see lipid experts. So, how do we find these patients? Sometimes we have patients -- two heterozygous -- who are attending a lipid clinic, they're going to have a child, and we can find this homozygous baby very early.

Much more commonly, certainly, the presentation that we see is the appearance of cutaneous xanthomata. Most of these children come because they develop planar xanthomata. Often in the ankle creases, popliteal fossa, cubital fossa, yellow infiltration of the skin, or flat plaques that are yellow. And that's the most common way that certainly patients present to us with these cutaneous xanthomata. Don't ignore them, don't misdiagnose them as we've seen happen as juvenile xanthogranuloma, etc.

So, that's the most common presentation, or occasionally the cholesterol is tested for some other reason, and then the very high cholesterol is found, so that's how most of these children present. Occasionally, if the diagnosis is missed, then, of course, the first presentation could be with a cardiovascular event and that's an absolute tragedy because that should have been avoided. So, we want to definitely find these patients early. Awareness of the risk of homozygous FH for your heterozygous patients: talk to them about it; if you're going to have a child, get your partner’s cholesterol tested if you are hypercholesterolemic. Then take these cutaneous xanthomata seriously. How do we confirm the diagnosis? In many cases, we can make a very confident clinical diagnosis. You have two parents who have heterozygous FH, they have this child with this LDL well above 13 mmol/L, the classical cutaneous stigmata: the diagnosis is quite certain.

Occasionally the phenotype can be a little bit less severe or intermediate, then one may not be quite as confident. Then, of course, we move on to genetics. And the genetics, how easy it depends is on what you have, for instance, in our country, South Africa, we have a lot of founder mutations, a lot of mutations that are very common. So, our genetics, we can often find the mutation quite rapidly because we just look for the common ones. But the technology has advanced so far and it's now pretty easy to get all the relevant gene sequences quickly and quite cheaply to make a genetic diagnosis. But I just want to emphasize, that if you don't have access to genetics, you can still make this diagnosis clinically. Don't not treat because 'oh, I can't do the genetics and I can't confirm this diagnosis.'

Dr Arca: Could you provide us with – you know the hallmark of homozygous FH is elevation of total cholesterol or LDL cholesterol – could you provide us with some numbers which can be helpful to suspect people with homozygous FH? Do you agree, for example, that the concentration of LDL cholesterol suggested by the guidelines and recommendation of 500 mg/dL is appropriate, or this could be readjusted according to the clinical history of that particular individual, that particular case?

Dr Blom: So, traditionally, the cutoffs of 13 mmol for the LDL, they certainly... If you've got an LDL above that you have a very, very high likelihood of having familial hypercholesterolemia in its homozygous form. We do know that there is more phenotypic variability with advanced genetic testing, so you can have a lower LDL cholesterol and some of those patients may appear to be clinically heterozygous. The good news is that in the trials they often do respond like clinical heterozygotes, as well. Maybe, I think, the whole thing that's going to guide our discussion today is: we treat the LDL, we don't treat the genes.

Dr Arca: Finally, according to the fact that in some countries, for example, in Italy, we need to have a genetic diagnosis proving the presence of 2 mutations in 2 different alleles. Do you advocate more larger employment of genetic diagnosis in this condition? Or again, we can stay, you can rely on the clinical phenotype?

Dr Blom: I'm a big fan of genetic diagnosis. And I think we should be using genetic diagnosis, and understand the disorder on a molecular level. Again, that becomes relevant later, when we talk about treatment: what type of mutation do you have? My point was really that if you can't do genetic diagnosis, don't give up, then you treat these patients based on clinical grounds. But I think genetics are important, they're very valuable, but they're not absolutely essential if you can't get them.

Dr Arca: Now, I would like to ask Eliot to address another important question. Relating how we can treat, and when to treat this very challenging condition?

Eliot A. Brinton, MD, FAHA, FNLA, FACE: Thank you, Marcello. So, the initial treatment is going to be diet and exercise. That is always helpful, but of course, in homozygous FH it is woefully inadequate. So, do your best with the patient, talking to them about saturated fat intake and physical activity, and weight management, although that's not very often a problem in homozygous patients. So we always start there. We control other cardiovascular risk factors. If the patient is a smoker, we have to make every possible effort for them to stop. Not very often, do we see diabetes, but, of course, that needs to be managed, hypertension, often present needs to be managed. So, please do all those things first. And then, of course, we start with pharmacotherapy, and we always start LDL treatment with a statin, and statins are well proven to be beneficial, except in homozygous FH. They have either very modest or possibly no benefit whatsoever.

And that's very surprising, very striking, but I think it's probably good to keep the patient on a statin assuming that they can tolerate it, and I think as high a dose as we can have them on is helpful. I always try to use ezetimibe, again, it often has very little apparent effect, but it probably has other effects beyond LDL. So, both for statins and ezetimibe, I'm a big fan of using these even though their effect tends to be modest or possibly absent. I also will always use a PCSK9 inhibitor; we have the monoclonal antibodies and we now have the new small interfering RNA (siRNA) drug. And again, their effect tends to be modest, they can have an effect in homozygous FH, but it's usually not as much as we would like to see, but I would always do that third.

So, I pretty much always have the patient on those 3 main classes of LDL receptor agents. Occasionally I might use bempedoic acid, that's another good agent, again, it works through the LDL receptor. That is really the basis and that's the background for treatment of homozygous FH. I love what Dirk said a minute ago about treating the patient and not the gene. With rare exception a patient who has homozygous FH will not be at treatment goal, despite all the treatments that I just mentioned. So, we do our best and we continue these treatments if they're tolerated and affordable by the patient or the patient's payer. Then we go to the treatment that is specific for homozygous FH and I think that's really, really important. So, almost always, these patients will under respond to the LDL receptor-mediated treatments, which I just mentioned. Why? Because homozygous FH is a disorder of the LDL receptor, either the gene itself or apoB or other related proteins.

And so, once we get to the point where we've done all those treatments, assuming that their LDL is still above the goal, and here in the US for somebody with prior cardiovascular events, the goal would be less than 70. It would be more aggressive less than 55, or even lower if they've had a recent event, or more severe events, or recurrent events -- all of those things would put the goal much lower still. So then, what will we do? Well, we've got to go onto our more specific treatments, and, by the way, just to comment data, for example, with evolocumab have shown that if you have a null mutation, you will not get any response at all to a PCSK9. So, they're very good, they're indicated for homozygous FH, but for the milder cases or the partial defects. So, I tend to start with apheresis, in part because I do apheresis here, but in part because it is more cost-effective. It's much less expensive than the other treatments I'm going to mention in a minute.

And there's a classic pattern to how LDL levels go with apheresis. They'll go down very dramatically with the treatment and then they go up very quickly. In the US and most of the world we do it every 2 weeks. So, there's an up and down a sawtooth pattern, but there's also what we call a ratchet effect where the pre-apheresis levels will tend to go down over time as you do serial apheresis. And, of course, the time-averaged LDL level is the most important, but certainly the up and down is fine. Apheresis in my mind works very well, and if it is available to the patient, I like to do that first because it is much less expensive than the other medications.

We have some data on long-term effects, not large, randomized trials, but there are data that show greater than a 50% reduction in cardiovascular events vs historical controls. And the adverse effects of apheresis tend to be quite few and generally quite minor. It has to be done carefully. It's best to, of course, do this with experienced personnel and an experienced center. But the adverse effects are modest. It is intrusive in the patient's lifestyle, but it's very, very effective.

Dr Arca: LDL apheresis is very demanding, not only for healthcare providers but also for the patient. Could you give us some idea of how difficult it is to keep the patients under treatment over time?

Dr Brinton: It really depends on the patient and the treating doctor and nurses in the center. And it depends on the patient, I mean, there's some patients who can't or won't do apheresis, they may stop after they've been doing it for a while. We're very successful in our particular center in having patients do this, many of our patients travel several hours, either by car or even by airplane, to come to our center. It's difficult, but we do our best and we do try to encourage our patients, and we've had a lot of success in that.

I was just going to mention in passing that the criteria for lipoprotein apheresis vary from country to country. So, look at your own country's guidelines and criteria and do what's appropriate for your patient, your center, and then, of course, for your country. And then just one other comment, please don't hesitate to refer to an apheresis center. Apheresis is available in most of the developed world and most patients do have access to this, of course, if a patient doesn't, then you can't do it. But don't hesitate to refer to an apheresis center near you and near your patient, of course.

Dr Arca: But now we also have other pharmacological options.

Dr Brinton: That is where I'm going to spend the rest of my brief time here There are two of them currently available, the microsomal triglyceride transfer protein (MTP) inhibitor lomitapide, and then this new drug the ANGPTL3 inhibitor which is evinacumab. So, let's talk about lomitapide, we have good data that we get on average, under ideal circumstances, about a 50% LDL lowering is very much dose dependent and dependent on the patient. And there's a whole range of response as you would expect, with some patients getting extremely good response and other patients getting very little response. Although the homozygous patients who do not respond to lomitapide are generally those who have severe gastrointestinal (GI) side effects, and they never can get past a very low dose.

So, the dose titration is critical, the dose-response is critical, and the efficacy in long-term is excellent. Again, assuming that the patient can tolerate a reasonable dose, but here's where, and this is all independent of the mutation. So, this is very, very helpful, very exciting, but it's an interaction between the clinician and the patient. You've got to start at a low dose, you've got to up titrate very gradually, you've got to talk with the patient go back down in the dose if you need to, keep them at a low dose for a long period of time. All these things are very, very helpful because you want to titrate carefully to the maximally tolerated dose. We always say this for statins, but it's absolutely critical for long-term success with lomitapide. I find that nearly all my patients who have ever tried lomitapide are able to tolerate it, even though some may never tolerate more than just a low dose, it tends to be helpful, even at a low dose, and the higher you can go over time with the dose, the better the response.

The long-term data with cardiovascular disease (CVD) reduction is excellent. Again, these are not large randomized controlled trials, but the historical comparison, the reduction of cardiovascular disease is dramatic. It is in the neighborhood of two-thirds of a reduction, which is spectacular for a homozygous patient. And, of course, extremely helpful because they have so many events and such a high-risk, the data are very impressive. And I think we need to keep this in mind, both for apheresis, as I mentioned already, but also for lomitapide, long-term data are excellent in terms of CVD efficacy. The same is true for long-term side effects, the GI side effects tend to go down dramatically over time. In most patients the side effects are not severe.

The safety threat is basically the fat in the liver and there is an increase in fat content of the liver. This occurs very early on, within a few months of starting the treatment with lomitapide. We're not required to monitor fat, but we are required to monitor transaminase levels, and there's a risk evaluation and mitigation strategy (REMS) programs in the US that we use to carefully monitor for that. The good news is that the long-term follow-up has not shown any progressive increase in hepatic fat.

So, the liver fat goes up a little bit in almost everybody, and then it stays slightly elevated long-term. We've got 5-year plus data, and it's really very reassuring that the hepatic fat does not progressively increase, it stays in the mild range in virtually all of our patients. And the same is true for the transaminases, which is generally how we monitor it. There has been careful follow-up in terms of hepatic fibrosis for elastography that's, of course, our concern. We don't want to have a patient go on to get cirrhosis. There is very good evidence now in long-term follow-up that fibrosis does not occur. So, there is an increase in fat, but there's no progression of fat and no progression of fibrosis. As far as I'm aware, there's never been a case of cirrhosis on lomitapide. So, that's very reassuring.

Also, hepatic fat may increase insulin resistance. There's good long-term follow-up to show that there is no adverse effect of lomitapide on insulin resistance. And the same is true for inflammation just using high sensitivity C-reactive protein (hsCRP) as our measure of overall inflammation, that does not increase long-term. It gives us a lot of flexibility, which I think is a benefit, excellent LDL lowering for homozygous patient anywhere near 25% to 50% or higher is what we see. Tolerability tends to be very good, if we work with the patient. The safety seems to be excellent, although we, of course, will follow the safety criteria appropriate for our country, and we will follow that very carefully in each and every patient.

So, evinacumab, our brand-new medication in homozygous FH, is an ANGPTL3 inhibitor and ANGPTL3 itself inhibits lipoprotein lipase and endothelial lipase. So, inhibiting the inhibitor, of course, will up-regulate lipoprotein lipase and endothelial lipase. We've never thought that this has much to do with LDL metabolism, but it turns out that this drug works very nicely for LDL lowering, roughly a 50% on average LDL reduction, very similar to lomitapide. Very nice data so far, in terms of short term-safety, it seems to be very well-tolerated, perhaps a little flu-like symptom or something, but generally very well-tolerated, safety seems to be excellent. We don't have any data regarding cardiovascular disease, but it's already been tested and approved in older children and adolescents, and it is currently being studied in younger children. So, this is an excellent complement to lomitapide treatment.

Dr Arca: Thank you for this overview about the possibilities we have totreat homozygous FH. Let's move on to clinical cases now, just to put on the ground what we have discussed so far. So, let’s start with a pediatric case, so that I would like to ask Dirk to present his very young homozygous FH patient. Please, Dirk?

Dr Blom: Thanks very much. I'd like to tell you about one of our patients whom I first saw when he was about 16 months old, and he was the first child and the parents knew that the dad had hypercholesterolemia. And so, they actually asked the general practitioner to test the child's cholesterol, and the cholesterol was very high with an LDL of about 16.5 mmol per litter. They, obviously, came to see us and we subsequently found out that the mother was hypercholesterolemic as well, although not quite as severe, and then we made a genetic diagnosis. So, both the parents have some of the common founder mutations that we see in South Africa with the dad's being a receptor negative mutation and the mom having a defective mutation, with a little bit of residual activity. And so, this was a very early presentation and we started him on treatment at diagnosis.

And just to briefly summarize what happened with him over the years, he started on statins, then, when the ezetimibe became commercially available, he started on that. He was on plasma exchange for many years because we don't have access to specific lipid apheresis. So, we do plasma exchange, which achieves the same, it's just a much more brutal procedure in the sense of you throwing away all the plasma and replacing it with an albumin solution, but you still do lower the LDL cholesterol. And subsequently, he's been on both a PCSK9 inhibitor and lomitapide. He hasn't had access to evinacumab as yet, but we've achieved quite good LDL cholesterol control for him over the years. So, that's a long history, but again, it shows the benefit of getting in there early. And he's really an example of somebody who started off when there was just statin and apheresis available. And now, in the last 20 years, we've had all these wonderful treatments become available.

Dr Arca: I want just to ask you a question, when you have in front of you a very young patient with a homozygous FH, according to your opinion, should be better to start all the medication we have together, or you are more inclined to prefer a stepwise approach?

Dr Blom: So, my approach has been to start statins and ezetimibe together at once, see what the effect of that is, and that you can see in 2 or 3 months time quite easily. And then add a PCSK9 inhibitor, see what the effect is of that. Because, again, it also just helps you, if parents are paying out of their own pocket, they need to know what is the value that the drug is adding for the patient. Is the patient responding? And then you would start your next therapeutic option, and that, in many countries, will simply depend on what you've got access to. If you can do apheresis, you're going to do apheresis; if you can get lomitapide you're going to do lomitapide; if you can get evinacumab you're going to do that. So that fourth step, I think, is going to be variable according to what you have access to.

Dr Arca: Now we are going to move on to an adult case. I would like to ask Eliot to present quickly this clinical case.

Dr Brinton: So, my case is a 55-year-old Native American female. She's got some central obesity, metabolic syndrome, prediabetes, and hypertension -- a very strong family history. We don't know her baseline LDL, but it may have been less than a 10 mmol/L or less than 390 mg/dL. The first data that I had on her: she was already on atorvastatin 40 mg and also on lomitapide 20 mg. This was started before I saw her. She had hypertension since being a teenager, she had a heart attack and an angioplasty at age 41. Then, she had repeat angioplasties at age 43, 44, and 46, she then she had a transient ischemic attack and then a coronary bypass. So, lots and lots of disease but happening later in life, as we will see often with our adult patients.

And then just to look at her treatment briefly. Interestingly, she was on atorvastatin and lomitapide, I don't know that she was carefully up-titrated as this was done before I saw her, and on 20 mg per day; she was having GI symptoms, so that had to be stopped. As soon as the PCSK9 inhibitors were available, she was treated with evolocumab, but had very severe flu-like illness and could not tolerate them. She then went on apheresis at our center with, of course, a very nice response, but it was still inadequate. We then added mipomersen, which was a great antisense oligonucleotide but, unfortunately, taken soon off the market, so we had to stop that, she had a very good response. And then, with the availability of evinacumab we started to run that. So, she's currently on 5 treatments, statin, ezetimibe, lomitapide, apheresis, and evinacumab, and she has had no further atherosclerosis events in the past 6 years.

So, we caught her kind of late, she'd had a lot of events before she came to our center, but with a very aggressive 5 agents or 5 treatment modalities, she's had a very nice course and she's tolerating apheresis and evinacumab and lomitapide. She's now on 20 mg of lomitapide we may try to go up a little higher on the dose because we really want to get her LDL as low as possible. Her LDL gets in the 30 to 40 mg/dL range after treatment (immediately after), but we really want to get it even lower. We like to have her time averaged below 40 or 55, if we could. So anyway, very interesting case.

Dr Arca: Question also for you. Do you think that, to manage homozygous FH, we need to know the vascular status of the patient?

Dr Brinton: So, the quick answer is: it's helpful to know the vascular status, especially if we're treating a young child, where they haven't had any events, we may want to do fairly aggressive monitoring of their atherosclerosis. In adults, they've pretty much always had cardiovascular events. And so, I don't go out of my way to monitor that, I mean, we could if it's indicated, but I'm simply looking at their events and I'm trying to prevent all future events, which we did manage to do in this one case. So, I think it's actually less important if they've already had cardiovascular events, you just treat as aggressively as you possibly can. And then you hope that there are no more events. And usually, the events are either zero or very, very few in the future.

Dr Arca: OK, thank you. I want just to make a short summary with a few take-home messages. And speaking about the diagnosis, so I think that the recognition of homozygous FH can be based on measuring LDL cholesterol, in performing very accurate family history, and also looking for physical signs. And really is not necessary, even though can be very helpful, it's not really necessary to perform genetics in these individuals. In addition, we have a large armamentarium of medication, we don't have only LDL apheresis, but we can add to LDL apheresis other drugs. One of the most important one is lomitapide, which has been demonstrated to be useful, very effective in controlling LDL cholesterol, with very few and manageable side effects. Even though it's a very new drug, we don't have extensive long-term follow-up, we can say that the data already collected are reassuring in terms of safety, liver safety, and GI safety.

And we can expect that with longer follow-up, we can also see some decline in the cardiovascular events in homozygous FH exposed to lomitapide. And also, we have new drugs, like evinacumab. So that hopefully, this is my opinion, when we will be able, in a very severe homozygous FH to combine all this medication and all this approach, I'm very convinced that in the future this will be not any more an incurable disease. We can cure this patient, we can provide a better life, and better cardiovascular prognosis.

The only problem is that we have to recognize that we have to make little more effort and try to identify them in the general population of people with hypercholesterolemia. And this is the message we want to leave to all of you. I want to thank all of you for participating in this activity. I want to thank my colleagues for their contribution to reviewing the characteristics and the management of homozygous FH patients. And then, I want also to remind you to continue to answer the questions to complete the evaluation of this program. And I want to say hello to all of you.

« Return to: Identify And Act: Overcoming Barriers to Managing Homozygous Familial Hypercholesterolemia
  • Print