PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

MedicalResearch.com: What should readers take away from your report?

Response: The importance of the present results derives from the possibility that a mechanism other than more efficient LDL receptors-mediated removal of LDL accounted for some of the very significant reductions in plasma LDL cholesterol and LDL-apoB levels observed during alirocumab treatment. These are also the first human data supporting prior studies in cells and mice that showed increased LDL receptor activity when PCSK9 is inhibited.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: As this study demonstrate that inhibition of with alirocumab increases the removal of LDL from the circulation via the LDL receptors, our confidence increases that the ongoing cardiovascular outcome trials will confer clinical benefit. These results also raise the possibility that increased VLDL clearance might also occur in people with high levels of triglycerides, expanding the benefits of alirocumab. 

MedicalResearch.com: Is there anything else you would like to add?

Response: This study adds to the scientific body of evidence supporting the efficacy of alirocumab and PCSK9 inhibitors in general in reducing LDL cholesterol. These results contribute to the meaningful value alirocumab provides to appropriate patients and to the overall healthcare system.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Effects of PCSK9 Inhibition with Alirocumab on Lipoprotein Metabolism in Healthy Humans

Circulation. 2017;135:352–362. DOI: 10.1161/CIRCULATIONAHA.116.025253

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Last Updated on February 13, 2017 by Marie Benz MD FAAD