Effect of evolocumab on lipoprotein particles

Journal article

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 DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1,077 nmol/L for the placebo group and 1,100 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 VLDL-P, small VLDL-P, and IDL-P: median (Q1, Q3) changes were –15.2% (–48, 48), –29% (–54, 18), and –36% (–70, 22), respectively. Mean (95% CI) percent changes in total LDL particle size in the evolocumab group was –1.7 (–2.0, –1.4); percent 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 (versus placebo) were all significant (P < .001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.

Authors: Toth, PP; Sattar, N; Blom, DJ; Martin, SS; Jones, SR

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: American Journal of Cardiology
• Volume: 121
• Issue: 3
• Pages: 308-314
• Publication date: 2017-11-08
• Acceptance date: 2017-10-26
• DOI: 10.1016/j.amjcard.2017.10.028
• EISSN: 1879-1913
• ISSN: 0002-9149
• Keywords: remnant lipoproteins; evolocumab; lipoprotein; cholesterol