Effect of evolocumab on cholesterol synthesis and absorption[S]

Journal of Lipid Research

Ren Xu¹  Robert Scott²  Scott M. Wasserman²  Matthew Peach²  C. Stephen Djedjos²  Dan Fitzpatrick²  Lisa Hamilton²  Ransi Somaratne³ 

[1] To whom correspondence should be addressed.;Amgen Inc., Thousand Oaks, CA;Amgen Ltd., Uxbridge, United Kingdom;

关键词: cholesterol/absorption;    cholesterol/biosynthesis;    lipids;    low density lipoprotein;    drug therapy;    proprotein convertase subtilisin/kexin type 9;   

DOI  :  

来源: DOAJ

【 摘 要 】

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in β-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.

【 授权许可】

Unknown