Abstract
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.
Highlights
The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis and those that reduce cholesterol absorption, on cholesterol absorption and synthesis are well understood
LDL-C was reduced by 39–51% and total cholesterol (TC) was reduced by 27–34% relative to baseline after 12 weeks of evolocumab therapy [33]
When data were expressed as a ratio to TC to account for the clearance of -sitosterol and campesterol associated with the clearance of circulating lipoproteins, treatment with evolocumab as a monotherapy resulted in increases in these ratios from baseline
Summary
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. At 2 weeks, changes in -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. 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, M., R. Effect of evolocumab on cholesterol synthesis and absorption. Plasma concentrations of the cholesterol precursors, lathosterol and desmosterol, are markers of cholesterol synthesis while plasma concentrations of the plant sterols, -sitosterol and campesterol, are markers of cholesterol absorption [7,8,9]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call