title: Antihyperlipidemic therapies targeting PCSK9.
abstract: Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins. A phase III clinical trial program evaluating clinical endpoints is now in progress. Other PCSK9-targeted approaches are in early stages of investigation, including natural inhibitors of PCSK9, RNA interference, and antisense inhibitors.
authors.affiliation: From the *Department of Medicine, North Shore Long Island Jewish Health System/Hofstra University School of Medicine, Manhasset, NY; and †New York Medical College/Westchester Medical Center, Valhalla, NY.
authors.forename: Michael
authors.initials: M
authors.lastname: Weinreich
authors.forename: William H
authors.initials: WH
authors.lastname: Frishman
mesh_terms: D000818:Animals; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D012697:Serine Endopeptidases / Q000235:genetics; D057170:Translational Research, Biomedical
chemical_list: D000960:Hypolipidemic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases