Effect of PCSK9 inhibition by alirocumab on lipoprotein particle concentrations determined by nuclear magnetic resonance spectroscopy

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. © 2015 the authors.