title: PCSK9 inhibitors: Novel therapeutic agents for the treatment of hypercholesterolemia.
abstract: Reducing plasma levels of low-density lipoprotein cholesterol (LDL-c) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, a substantial proportion of patients fail to achieve acceptable LDL-c levels with currently available lipid-lowering drugs. Over the last decade, inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has emerged as a promising target to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the LDL receptor for lysosomal degradation. Inhibition of PCSK9 increases expression of the LDL receptor. This observation has led to the development of a number of approaches to directly target PCSK9. Three monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials involving various patient categories on different background lipid lowering therapies. Current evidence shows reductions in LDL cholesterol levels of up to 70%, independent of background statin therapy. The results of phase 3 trials will demonstrate the long-term efficacy and safety of PCSK9 inhibition, and will indicate whether LDL-c lowering induced by this novel approach translates into beneficial effects on CVD outcome.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: Rutger
authors.initials: R
authors.lastname: Verbeek
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, the Netherlands; Departmen of Vascular Surgery, Academic Medical Center, the Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stoekenbroek
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, PO box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address: g.k.hovingh@amc.uva.nl.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D020868:Gene Silencing; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D011480:Protease Inhibitors; D043484:Proprotein Convertases
keywords: Alirocumab; Bococizumab; Evolocumab; PCSK9; Proprotein Convertase Subtilisin/Kexin type 9