Editor's Note: The following is an edited, translated transcript of a conversation taped in May 2015 between Boris Hansel, MD, endocrinologist-nutritionist, and Eric Bruckert, MD, PhD, a lipid management specialist, in France.
Dr Hansel: Hello, and welcome to Medscape for this second conversation devoted to familial hypercholesterolemia. In Part 1, we talked about screening, diagnosis, and the definition of familial hypercholesterolemia. Joining us again is Professor Eric Bruckert, chief of endocrinology and cardiovascular prevention at Hôpital de la Pitié-Salpêtrière in Paris.
Lifestyle and Dietary Intervention: Are They Effective in the Familial Forms?
Dr Hansel: Professor Bruckert,you're used to seeing patients with severe dyslipidemias, including familial hypercholesterolemias. In general, we know that lifestyle and dietary measures constitute the first line of treatment in hypercholesterolemia. The principles are very clear and widely agreed-upon.
First, reduce your saturated fat intake in favor of unsaturated fatty acids. In other words, reduce your intake of animal fats while increasing your intake of fats of plant origin, with the exception of palm oil. The second recommendation is to fill up on fiber, especially soluble fiber, and then reduce your dietary intake of cholesterol. These dietary measures are well recognized, and they are known to reduce the low-density lipoprotein (LDL) cholesterol level by 10%-15% on average when properly applied.
Are these dietary measures as effective in people with familial hypercholesterolemia, a genetic disorder characterized by very high levels? Patients always say to us, "But it's my body that's making all this cholesterol." So, are they useful and effective?
Dr Bruckert: This is a very important question. Actually, when we talk about a 10%-15% reduction, we're being very conservative, for there are studies that have shown that the LDL cholesterol level can be reduced by up to 30%.[1]
Dr Hansel: If you eat almonds, soy, et cetera.
Dr Bruckert: Yes; the impact is really significant. Dietary measures have a reputation for being ineffective in the familial forms, but actually, this is totally false. Why is this false? Because when you lower the LDL cholesterol level by 10% in a familial form, this means that there's a decrease of 20 mg. For a 20% reduction, there's a decrease of 40 mg, whereas this same 10% reduction in a milder, polygenic form of hypercholesterolemia translates into a smaller absolute reduction in the cholesterol level.
Dr Hansel: However, we're often disappointed with blood test results. Is this due to the fluctuations in the cholesterol level, which result in us not seeing the improvement? What should we tell our patients?
Dr Bruckert: It's true that if there's only a 10% reduction, this can fall within the range of spontaneous fluctuation. But I think we should explain to patients that the efficacy is real and that the benefit of dietary measures can go beyond this, for they protect the arteries independently of the cholesterol level. We have clearly seen the incredible impact of the Mediterranean diet on cardiovascular risk.[2]
Dr Hansel: ...which, independently of the effect on the cholesterol level, has reduced cardiovascular events.
Dr Bruckert: So, in my opinion, we should really encourage these individuals to adhere to dietary measures, which is often not all that complicated.
Statins: What Doses?
Dr Hansel: In every case, dietary measures are needed, but so is physical activity—which, even if it doesn't have an effect on cholesterol, will reduce the cardiovascular risk. However, we have to introduce pharmacologic treatments in every case, because as I recall, the European guidelines are in favor of lowering the LDL cholesterol level to below 100 mg/dL. There is a consensus regarding the initiation of statins. Should high doses be used at the outset, knowing that we are going to have to hit hard and use more potent statins?
Dr Bruckert: I don't think there is any question about initiating the most potent statins (atorvastatin, rosuvastatin). There's no debate about this. Now, I think it's a mistake to start off with high doses. There are a number of reasons for this:
The most important reason is that the response to statins is highly variable from one patient to another. In a familial form, if the patient's cholesterol level can be normalized with an entry-level dose, why administer a high dose?
The second reason concerns therapeutic management. It's difficult for patients to adhere to a treatment. Giving them a low dose first and then increasing the dose and going toward higher doses, if necessary, often fosters compliance. I therefore think it's a serious mistake to start off with high doses.
Dr Hansel: You recommend instead titration, assessing the side effects and the benefit, talking with the patient about them, and increasing the dose to that which will lower their LDL level to below 100 mg/dL.
Dr Bruckert: Absolutely.
Ezetimibe
Dr Hansel: So, if that doesn't work, ezetimibe is recommended. It's the second drug at our disposal that has a significant impact on the LDL cholesterol level. There's now evidence of cardiovascular prevention from the results of the IMPROVE-IT study in late 2014. So, ezetimibe is not prescribed systematically.[3]
Dr Bruckert: When we look at all the patients who have familial forms of hypercholesterolemia, it's true that most of the time, we have difficulty achieving the objective with treatment with a statin as monotherapy. Therefore, I think a lot of patients require ezetimibe.Furthermore, when an analysis was performed of the familial hypercholesterolemia patients in a large French registry of all the large centers that treat hyperlipidemic patients, it was found that most of them did not achieve the ideal objective of 100 mg/dL, even with the maximum treatment (statin plus ezetimibe).[4]
Alternatives: Cholestyramine, Apheresis, PCSK9 Inhibitors, Lomitapide
Dr Hansel: So, in practice: dietary measures, dose escalation of a statin and ezetimibe as soon as the maximum tolerated dose of the statin is reached. However, sometimes there are patients—and this is not unusual—who do not tolerate statins, who have symptoms, and who don't want to continue. Are there any alternatives to statins and ezetimibe?
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Eric Bruckert, Boris Hansel. Familial Hypercholesterolemia (Part 2): What Is the Optimal Treatment? - Medscape - Jun 11, 2015.
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