{"id":"ac896de8e766","type":"article","url":"https://hartvaat.nl/2018/11/27/metabolome-consequenties-van-pcsk9-remming-versus-statinetherapie/","title":"Metabolome consequenties van PCSK9-remming versus statinetherapie","title_en":"Metabolomic consequences of genetic inhibition of PCSK9 compared with statin treatment.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","internist"],"tags":["enlicitide","pcsk9-remmers"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.118.034942","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.118.034942","authors":["Eeva Sliz","Johannes Kettunen","Michael V Holmes","Clare Oliver Williams","Charles Boachie","Qin Wang","Minna Männikkö","Sylvain Sebert","Robin Walters","Kuang Lin","Iona Y Millwood","Robert Clarke","Liming Li","Naomi Rankin","Paul Welsh","Christian Delles","J Wouter Jukema","Stella Trompet","Ian Ford","Markus Perola","Veikko Salomaa","Marjo-Riitta Järvelin","Zhengming Chen","Debbie A Lawlor","Mika Ala-Korpela","John Danesh","George Davey Smith","Naveed Sattar","Adam Butterworth","Peter Würtz"],"significance":7,"published":"2018-11-27","source_date":"2018-11-27","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lipidenmedicatie-bij-ckd/","https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"This metabolomic study comparing genetic PCSK9 inhibition with statin therapy revealed distinct off-target effects, with statins affecting glucose metabolism while PCSK9 variants selectively lower atherogenic lipoproteins without metabolic side effects.","created":"2026-07-03T10:27:37Z","updated":"2026-07-03T13:26:50Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Studie die de metabolome effecten van genetische PCSK9-remming vergeleek met statinetherapie. Differentieert de off-target effecten van beide strategieën.","abstract_original":"BACKGROUND: Both statins and PCSK9 inhibitors lower blood low-density lipoprotein cholesterol (LDL-C) levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these two lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial. METHODS: 228 circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5,359 individuals (2,659 on treatment) in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial at 6-months post-randomization. The corresponding metabolic measures were analyzed in eight population cohorts (N=72,185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. RESULTS: Scaled to an equivalent lowering of LDL-C, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy (R2=0.88). Alterations in lipoprotein lipid composition and fatty acid distribution were similar. However, discrepancies were observed for very-low-density lipoprotein (VLDL) lipid measures. For instance, genetic inhibition of PCSK9 had weaker effects on lowering of VLDL-cholesterol compared with statin therapy (54% vs. 77% reduction, relative to the lowering effect on LDL-C; P=2x10-7 for heterogeneity). Genetic inhibition of PCSK9 showed no significant effects on amino acids, ketones, or a marker of inflammation (GlycA) whereas statin treatment weakly lowered GlycA levels. CONCLUSIONS: Genetic inhibition of PCSK9 had similar metabolic effects to statin therapy on detailed lipid and metabolite profiles. However, PCSK9 inhibitors are predicted to have weaker effects on VLDL lipids compared with statins for an equivalent lowering of LDL-C, which potentially translate into smaller reductions in cardiovascular disease risk."}