Lomitapide affects HDL composition and function

• Published in: Atherosclerosis Vol. 251; pp. 15 - 18
• Main Authors: Yahya, R, Favari, E, Calabresi, L, Verhoeven, A.J.M, Zimetti, F, Adorni, M.P, Gomaraschi, M, Averna, M, Cefalù, A.B, Bernini, F, Sijbrands, E.J.G, Mulder, M.T, Roeters van Lennep, J.E
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-08-2016
• Subjects: Adult; Atherosclerosis; ATP Binding Cassette Transporter 1 - genetics; Benzimidazoles - pharmacology; Cardiovascular; Cholesterol - metabolism; Cholesterol efflux capacity; Cholesterol lowering drugs; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Female; HDL; Homozygote; Homozygous familial hypercholesterolemia; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - genetics; Lipoproteins, HDL - blood; Lipoproteins, HDL - drug effects; Lomitapide; Male; Phenotype; Treatment Outcome; Young Adult; HDL; Cholesterol lowering drugs; Lomitapide; Homozygous familial hypercholesterolemia; Cholesterol efflux capacity
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2016.05.005

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.