Effect of PCSK9 Inhibition by Alirocumab on Lipoprotein Particle Concentrations Determined by Nuclear Magnetic Resonance Spectroscopy

Michael J Koren, Dean Kereiakes, Ray Pourfarzib, Deborah Winegar, Poulabi Banerjee, Sara Hamon, Corinne Hanotin, James M McKenney, Michael J Koren, Dean Kereiakes, Ray Pourfarzib, Deborah Winegar, Poulabi Banerjee, Sara Hamon, Corinne Hanotin, James M McKenney

Abstract

Background: In patients with discordance between low-density lipoprotein (LDL) cholesterol and LDL particle (LDL-P) concentrations, cardiovascular risk more closely correlates with LDL-P.

Methods and results: We investigated the effect of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, on lipoprotein particle concentration and size in hypercholesterolemic patients, using nuclear magnetic resonance spectroscopy. Plasma samples were collected from patients receiving alirocumab 150 mg every 2 weeks (n=26) or placebo (n=31) during a phase II, double-blind, placebo-controlled trial in patients (LDL cholesterol ≥100 mg/dL) on a stable atorvastatin dose. In this post hoc analysis, percentage change in concentrations of LDL-P, very-low-density lipoprotein particles, and high-density lipoprotein particles from baseline to week 12 was determined by nuclear magnetic resonance. Alirocumab significantly reduced mean concentrations of total LDL-P (-63.3% versus -1.0% with placebo) and large (-71.3% versus -21.8%) and small (-54.0% versus +17.8%) LDL-P subfractions and total very-low-density lipoprotein particle concentrations (-36.4% versus +33.4%; all P<0.01). Total high-density lipoprotein particles increased with alirocumab (+11.2% versus +1.4% with placebo; P<0.01). There were greater increases in large (44.6%) versus medium (17.7%) or small high-density lipoprotein particles (2.8%) with alirocumab. LDL-P size remained relatively unchanged in both groups; however, very-low-density and high-density lipoprotein particle sizes increased to a significantly greater extent with alirocumab.

Conclusions: Alirocumab significantly reduced LDL-C and LDL-P concentrations in hypercholesterolemic patients receiving stable atorvastatin therapy. These findings may be of particular relevance to patients with discordant LDL-C and LDL-P concentrations.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT01288443" title="See in ClinicalTrials.gov">NCT01288443.

Keywords: alirocumab; lipoprotein particle number; lipoprotein subfractions; nuclear magnetic resonance spectroscopy; proprotein convertase subtilisin/kexin type 9 inhibitor.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Change in lipoprotein particles from baseline to week 12 (individual patient data, n=26 alirocumab, n=31 placebo). A. Total LDL‐P. B, Total HDL‐P. C, Total vLDL‐P and chylomicron particles. HDL‐P indicates high‐density lipoprotein particles; LDL‐P, low‐density lipoprotein particles; vLDL‐P, very‐low‐density lipoprotein particles; P, particles.

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