Effects of PCSK9-Antibodies on Cholesterol Metabolism

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have been shown in the large-scaled FOURIER study and the ODYSSEY OUTCOMES study to reduce cardiovascular endpoints. It is not completely understood how PCSK9-antibodies affect cholesterol synthesis and absorption and circulating PCSK9 levels. Moreover, the implications of lipid-lowering pretreatment with statins and/or ezetimibe on treatment with PCSK9-antibodies are unclear. In an observational cross-sectional and longitudinal clinical trial 245 patients with hypercholesterolemia received PCSK9-antibodies. At the beginning of therapy with PCSK9-antibodies and 4 - 8 weeks after starting therapy with PCSK9-antibodies blood samples were taken. We measured the non-cholesterol sterols campesterol and sitosterol as markers of cholesterol absorption and lathosterol as a marker of cholesterol synthesis. 84 of the participants had no pretreatment, 26 with ezetimibe, 38 with statins and 97 with ezetimibe and statins. With intensified pretreatment circulating PCSK9 increased significantly. Therapy with PCSK9-antibodies resulted in an increase of circulating PCSK9 of 760 ± 45 %, a decrease of total cholesterol by -38.8 ± 0.9 %, a decrease of LDL-C by -52.1 ± 1.7 %, an increase of HDL-C by 13.8 ± 1.5 % and a decrease of total triglycerides by -17.1 ± 1.8 % (all p

Date of Award	2019
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Günther Silbernagel (Supervisor) & Günter Fauler (Co-supervisor)