Management of patients with familial hypercholesterolaemia

Nat Rev Cardiol. 2015 Oct;12(10):565-75. doi: 10.1038/nrcardio.2015.92. Epub 2015 Jun 16.

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.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Disease Management*
  • Genetic Therapy
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II / diagnosis
  • Hyperlipoproteinemia Type II / genetics
  • Hyperlipoproteinemia Type II / therapy*
  • Liver Transplantation
  • Practice Guidelines as Topic
  • Prevalence
  • Risk Factors

Substances

  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors