Lomitapide affects HDL composition and function

Atherosclerosis. 2016 Aug:251:15-18. doi: 10.1016/j.atherosclerosis.2016.05.005. Epub 2016 May 11.

Abstract

Background: Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH).

Methods and results: Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range -34 to -89%). Total HDL-C levels decreased (range -16 to -34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range -39 to -99%). The changes of total, ABCG1- and SR-BI-mediated CEC were less consistent.

Conclusion: Lomitapide decreased LDL-C and HDL-C levels. Our report raises the hypothesis that the anti-atherogenic potential of HDL seems to be unaffected as total CEC did not seem to change consistently. Combined with the reduction of atherogenic lipoproteins, the net effect of lomitapide appears to be beneficial in HoFH patients.

Keywords: Cholesterol efflux capacity; Cholesterol lowering drugs; HDL; Homozygous familial hypercholesterolemia; Lomitapide.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics*
  • Adult
  • Atherosclerosis
  • Benzimidazoles / pharmacology*
  • Cholesterol / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Female
  • Homozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / genetics
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL / drug effects*
  • Male
  • Phenotype
  • Treatment Outcome
  • Young Adult

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • BMS201038
  • Benzimidazoles
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Cholesterol