Effect of evolocumab on cholesterol synthesis and absorption.
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.
['Peach|Matthew|M|', 'Xu|Ren|R|', 'Fitzpatrick|Dan|D|', 'Hamilton|Lisa|L|', 'Somaratne|Ransi|R|', 'Scott|Robert|R|', 'Wasserman|Scott M|SM|', 'Djedjos|C Stephen|CS|']
D000328:Adult D000911:Antibodies, Monoclonal D061067:Antibodies, Monoclonal, Humanized D000924:Anticholesteremic Agents D008078:Cholesterol, LDL D005260:Female D006801:Humans D006937:Hypercholesterolemia D007408:Intestinal Absorption D008297:Male D008875:Middle Aged D012855:Sitosterols D016896:Treatment Outcome
statin proprotein convertase subtilisin/kexin type 9 cholesterol/absorption cholesterol/biosynthesis drug therapy lipid-lowering lipids low density lipoprotein