Physicians' Academy for Cardiovascular Education

PCSK9 inhibitor changes levels and sizes of lipoprotein particles

Effect of Evolocumab on Lipoprotein Particles

Literature - Toth PP, Sattar N, Blom DJ, et al. - Am J Cardiol 2018;121:308–314


The pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab decreases significantly LDL-c levels in various clinical settings, leading to a risk reduction of CV events. The impact on lipoprotein particles or particle subfractions is not clear [1-3].

In this post hoc analysis, the effect of evolocumab on lipoprotein particle concentrations and size was evaluated in the phase 3 DESCARTES (Durable Effect of PCSK9 Antibody Compared with Placebo Study) trial [4]. DESCARTES was a 52-week, randomized, double-blind, placebo-controlled, multicenter, global study of patients with hyperlipidemia. Eligible patients, aged 18-75 years, had LDL-c levels ≥1.9 mmol/L (75 mg/dL) and a fasting triglyceride level ≤4.5 mmol/L (400 mg/dL), despite optimal lipid lowering therapy, and were randomized 1:2 to receive placebo or evolocumab 420 mg monthly.

Lipids and lipoprotein particle analyses, that included LDL, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL)/chylomicrons, and remnant lipoproteins, including small VLDL and intermediate-density lipoprotein (IDL), were assessed by nuclear magnetic resonance (NMR) spectroscopy at baseline and at week 52, in 619 patients with all available data.

Main results


Evolocumab significantly changes lipoprotein particle number and size. Treatment with the PCSK9 inhibitor was associated with lower concentrations of total LDL-c, small LDL-p and large LDL-p. These findings may help guide therapeutic decisions in patients with hyperlipidemia.


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