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Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a)

Xiang Zhang1,2, Lotte C A Stiekema3, Erik S G Stroes3

  • 1Department of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. xiang.zhang@wur.nl.

Lipids in Health and Disease
|May 13, 2020
PubMed

Insights

Evolocumab, a PCSK9 inhibitor, significantly reduced lipoprotein(a) [Lp(a)] and VLDL particles in individuals with elevated Lp(a). The reduction in VLDL particles was linked to baseline Lp(a) levels.

Area of Science:

  • Cardiovascular Medicine
  • Metabolomics
  • Pharmacology

Background:

  • Elevated lipoprotein(a) [Lp(a)] is a significant risk factor for cardiovascular disease.
  • PCSK9 inhibitors lower LDL-C and Lp(a), but their effects on other metabolites are not fully understood.
  • This study investigates the impact of PCSK9 inhibition on lipoprotein subclasses, amino acids, and fatty acids.

Purpose of the Study:

  • To characterize the effects of PCSK9 inhibition with evolocumab on circulating metabolites in individuals with elevated Lp(a).
  • To assess the relationship between Lp(a) levels and lipoprotein subclasses following evolocumab treatment.

Main Methods:

  • Nuclear magnetic resonance (NMR) metabolomics was performed on plasma samples from 30 individuals with elevated Lp(a).
  • Participants were randomized to receive either placebo or evolocumab (420 mg Q4W) for 16 weeks.
  • Lognormal regression and multilevel multivariate regression analyses were used to assess treatment effects and interrelationships.

Main Results:

  • Evolocumab treatment led to a 17% reduction in circulating Lp(a) and decreased VLDL, IDL, and LDL particles.
  • Baseline Lp(a) concentrations correlated with the degree of reduction in triglyceride-rich VLDL particles.
  • Lipid content of VLDL, IDL, and LDL particles was also substantially reduced.

Conclusions:

  • PCSK9 inhibition with evolocumab effectively reduces VLDL particle concentrations alongside LDL-C.
  • The magnitude of VLDL particle reduction is dependent on baseline Lp(a) levels.
  • Findings indicate a significant impact of evolocumab on VLDL metabolism in individuals with elevated Lp(a).
Abstract

Keywords:
EvolocumabLipoprotein(a)MetabolomicsPCSK9 antibodiesVLDL

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