Abstract 17313: Alirocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibody, Reduces Cholesterol Concentrations of All Serum Low-Density Lipoprotein Cholesterol Fractions
Introduction: Low-density lipoprotein cholesterol (LDL-C) is composed of a variety of LDL particles of different densities and states of lipidation. Analysis of effects of lipid-modifying therapies on LDL-C particle composition may aid understanding of treatment mode-of-action.
Hypothesis: Alirocumab reduces LDL-C by decreasing multiple LDL-C fractions.
Methods: Three multicenter, double-blind, parallel-group, placebo-controlled trials were conducted in patients with primary hypercholesterolemia (565 [NCT01288443], N=183; 566 [NCT01288469], N=92) or heterozygous familial hypercholesterolemia (1003 [NCT01266876], N=77). Patients (receiving statins+/-ezetimibe) were treated with alirocumab 50-150 mg every 2 wks (Q2W) or 150-300 mg every 4 wks, depending on the study, providing reductions in mean LDL-C of up to 72.4%. In post hoc analyses, lipoproteins were subfractionated by vertical auto profile (VAP) testing. Percent change in LDL1-C ("large buoyant" LDL), LDL2-C, LDL3-C, and LDL4-C ("small, dense" LDL) levels in patients receiving alirocumab 150 mg Q2W (a dose common to all 3 trials) vs. placebo from baseline to wk 12 for 565, wk 8 for 566, and wk 6 for 1003 were assessed using ANCOVA.
Results: Reductions in cholesterol content of the LDL-C fractions were observed in patients receiving alirocumab 150 mg Q2W in the 3 studies, vs. placebo (Table). Treatment-emergent adverse events (TEAEs) occurred in 54.5% with placebo vs. 58.3% of patients receiving alirocumab 150 mg Q2W. The most common TEAEs were injection site reactions, typically of mild intensity and short duration.
Conclusions: Therapy with alirocumab significantly reduced cholesterol concentrations in LDL-C fractions separable by VAP. Previously demonstrated LDL-C reductions with alirocumab were confirmed across the spectrum of LDL-C sub-fractions. The potential clinical impact of alirocumab on these important variables warrants further investigation.
- © 2013 by American Heart Association, Inc.