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  • Review Article
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Management of patients with familial hypercholesterolaemia

Nature Reviews Cardiology volume 12, pages 565–575 (2015)Cite this article

Subjects

Key Points

  • Familial hypercholesterolaemia (FH), one of the most common genetic disorders, is characterized by lifelong elevated LDL-cholesterol (LDL-C) levels and is associated with increased risk of premature coronary heart disease and death

  • Current FH treatments are often suboptimal; high-intensity statin is an established treatment for patients with FH, but most patients treated with statin monotherapy fail to achieve LDL-C target levels

  • Ezetimibe can be added to statin treatment to achieve LDL-C target levels

  • Apheresis is used with high-intensity statin therapy in patients with homozygous FH or in statin-refractory patients with heterozygous FH, with or without ezetimibe

  • Mipomersen, an inhibitor of apolipoprotein B-100 synthesis, and lomitapide, a microsomal triglyceride transfer protein inhibitor, reduce LDL-C levels when used with high-intensity statin therapy, but both increase liver fat content

  • PCSK9 inhibitors (alirocumab and evolocumab) seem to be the most promising emerging treatment option, are well tolerated, and reduce LDL-C levels further in patients who are already receiving maximally-tolerated statin treatment

Abstract

Familial hypercholesterolaemia (FH) is an autosomal inherited disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels and an increased risk of premature atherosclerotic cardiovascular disease. Although FH is one of the most common genetic disorders, this disorder remains mostly undetected and its management is often suboptimal. High-intensity statins are standard treatment for patients with FH, but LDL-C levels in most patients treated with statin monotherapy remain above those recommended by guidelines. Combination therapy to lower LDL-C levels further—such as treatment with statins plus ezetimibe—has been successful, and combination of apheresis with high-intensity statin treatment is used in patients with homozygous FH and in those with heterozygous FH who are statin-refractory. Mipomersen, an inhibitor of apolipoprotein B-100 synthesis, and lomitapide, a microsomal triglyceride transfer protein inhibitor, reduce LDL-C levels further when added to high-intensity statin treatment in homozygous FH, but both have important adverse effects, such as increasing liver fat content. At present, PCSK9 inhibition (with alirocumab or evolocumab) is well tolerated and reduces LDL-C levels considerably in patients receiving the maximally tolerated statin treatment, and seems the most promising emerging treatment option. Nevertheless, data from outcome trials with hard end points for PCSK9 inhibitors, mipomersen, and lomitapide are still needed before these therapies become standard for patients with FH.

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Figure 1: Mipomersen—mode of action.
Figure 2: Lomitapide—mode of action.
Figure 3: PCSK9 inhibitors—mode of action.

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  1. Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Kispaticeva 12, Zagreb, 10000, Croatia

    Željko Reiner

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  1. Željko Reiner
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Correspondence to Željko Reiner.

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Ž.R. has received honoraria and is an advisory board member for Sanofi Aventis.

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Reiner, Ž. Management of patients with familial hypercholesterolaemia. Nat Rev Cardiol 12, 565–575 (2015). https://doi.org/10.1038/nrcardio.2015.92

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