Effect of Evolocumab on Lipoprotein Particles

Peter P. Toth, Naveed Sattar, Dirk J. Blom, Seth Martin, Steven Jones, Maria Laura Monsalvo, Mary Elliott, Mike Davis, Ransi Somaratne, David Preiss

Research output: Contribution to journalArticle

Abstract

The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were −15.2% (−48, 48), −29% (−54, 18), and −36% (−70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was −1.7 (−2.0, −1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalAmerican Journal of Cardiology
Volume121
Issue number3
DOIs
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Effect of Evolocumab on Lipoprotein Particles'. Together they form a unique fingerprint.

  • Cite this

    Toth, P. P., Sattar, N., Blom, D. J., Martin, S., Jones, S., Monsalvo, M. L., Elliott, M., Davis, M., Somaratne, R., & Preiss, D. (2018). Effect of Evolocumab on Lipoprotein Particles. American Journal of Cardiology, 121(3), 308-314. https://doi.org/10.1016/j.amjcard.2017.10.028