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Published on: November 10, 2017
Lomitapide affects HDL composition and function
R Yahya1, E Favari2, L Calabresi3
1Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
Insights
Lomitapide treatment in homozygous familial hypercholesterolemia (HoFH) patients reduced LDL-C and HDL-C. Cholesterol efflux capacity (CEC) changes were variable, suggesting potential benefits despite HDL-C reduction.
Area of Science:
- Cardiology
- Pharmacology
- Metabolic Disorders
Background:
- Lomitapide effectively lowers low-density lipoprotein-cholesterol (LDL-C).
- Lomitapide's impact on high-density lipoprotein-cholesterol (HDL-C) and its functional capacity requires further investigation.
- Understanding these effects is crucial for optimizing treatment in homozygous familial hypercholesterolemia (HoFH).
Purpose of the Study:
- To investigate the effect of lomitapide on HDL-C levels in HoFH patients.
- To assess the impact of lomitapide on the cholesterol efflux capacity (CEC) of HDL.
- To evaluate the overall clinical efficacy of lomitapide in HoFH.
Main Methods:
- Four HoFH patients received escalating doses of lomitapide.
- Measurements included LDL-C, HDL-C levels, and HDL-mediated cholesterol efflux capacity (CEC).
- Specific CEC pathways (ABCA1, ABCG1, SR-BI) were analyzed.
Main Results:
- Lomitapide significantly decreased LDL-C (–34% to –89%) and total HDL-C (–16% to –34%).
- A shift towards more buoyant HDL particles was observed.
- ABCA1-mediated CEC significantly decreased (–39% to –99%), while other CEC pathways showed inconsistent changes.
Conclusions:
- Lomitapide reduces both LDL-C and HDL-C levels in HoFH patients.
- The anti-atherogenic potential of HDL may be preserved as total CEC did not consistently decrease.
- The combined reduction of atherogenic lipoproteins and preserved HDL function suggests a net beneficial effect of lomitapide in HoFH.
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.
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