In short Article

PCSK9 inhibitors for familial hypercholesterolaemia

An elevated LDL-cholesterol concentration is one of the risk factors for atherosclerotic vascular disease that can be modified by lifestyle interventions or medication. Due to their greatly elevated LDL-cholesterol level, patients with familial hypercholesterolaemia (FH) have a high risk of developing this form of vascular disease at a young age. Lowering the LDL-cholesterol concentration nearly always requires pharmacotherapy. So far, however, no randomised studies among patients with FH have been conducted to investigate the effect of lowering LDL-cholesterol levels on cardiovascular endpoints. Findings of observational studies suggest that lowering the cholesterol, the dominant risk factor in FH, reduces the risk of atherosclerotic vascular disease, while randomised studies have shown the effect of lowering LDL-cholesterol levels in patients without FH. In addition, randomised research has shown that PCSK9 (proprotein-convertase subtilisin-kexin type 9) inhibitors, combined with a statin, further lower LDL cholesterol in patients without FH, and could thus also be useful. In view of their relatively high price, the use of PCSK9 inhibitors is limited to patients with a high cardiovascular risk and an excessive LDL-cholesterol concentration according to the guidelines, despite treatment with regular cholesterol-lowering agents, such as a potent statin and ezetimibe, at the maximum tolerable dosage.

What is Ge-Bu’s opinion?
  • There have been no randomised studies investigating the effect of lowering LDL-cholesterol concentrations on the risk of atherosclerotic vascular disease in patients with familial hypercholesterolaemia. Such studies are ethically unacceptable will therefore not be conducted.
  • The results of observational studies show that for patients with familial hypercholesterolaemia, there is a causal relationship between the LDL-cholesterol concentration and the development of atherosclerotic vascular disease.
  • Randomised, placebo-controlled studies have found that the use of PCSK9 inhibitors causes a further lowering of LDL-cholesterol concentrations by 50% in patients with heterozygous familial hypercholesterolaemia who are already being treated with a statin and/or ezetimibe.
  • Based on national and international guidelines, the effect of PCSK9 inhibitors for the treatment of heterozygous familial hypercholesterolaemia is assumed to have been sufficiently proven to improve the prognosis regarding atherosclerotic vascular disease.

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The literature refers to the Dutch text


  • Melvin Lafeber
  • Gerard A. Rongen, Prof dr, vascular internist and clinical pharmacologist Department of Internal Medicine
    Radboudumc, Nijmegen
    the Netherlands