title: PCSK9 inhibition: the way forward in the treatment of dyslipidemia.
abstract: Barely a decade after the discovery of the gene encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and its recognition as a key player in cholesterol metabolism, PCSK9 inhibition is now considered an exciting approach in the reduction of residual risk of cardiovascular disease. The progress from PCSK9 discovery to the development of targeted treatment has been unprecedented in terms of scale and speed. The first suggestion of a link between PCSK9 and hypercholesterolemia was published in 2003; a decade later, two meta-analyses of clinical trials comparing anti-PCSK9 treatment to placebo or ezetimibe, including >10,000 hypercholesterolemic individuals, were published. Currently, three PCSK9 inhibitors are being evaluated in clinical outcome trials and the results will determine the future of these lipid-lowering therapies by establishing their clinical efficacy in terms of cardiovascular event reduction, safety, and the consequences of prolonged exposure to very low levels of LDL-cholesterol. Irrespective of their outcomes, the exceptionally rapid development of these drugs exemplifies how novel technologies, genetic validation, and rapid clinical progression provide the tools to expedite the development of new drugs.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. r.m.stoekenbroek@amc.uva.nl.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stoekenbroek
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. j.j.kastelein@amc.uva.nl.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. r.huijgen@amc.uva.nl.
authors.forename: Roeland
authors.initials: R
authors.lastname: Huijgen
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D050356:Lipid Metabolism / Q000187:drug effects; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000627:therapeutic use; D040242:Risk Reduction Behavior; D012697:Serine Endopeptidases
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D011480:Protease Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases