title: Proprotein convertase subtilisin kexin 9 inhibitors: next generation in lipid-lowering therapy.
abstract: BACKGROUND
  Statins reduce low-density lipoprotein cholesterol (LDL-C) and are currently the mainstay in the treatment of hyperlipidaemia and subsequently the prevention of atherosclerotic cardiovascular disease (CVD). Nevertheless, there is a need to further lower LDL-C, especially in subjects with severe forms of hypercholesterolaemia despite maximum doses of conventional drugs and/or in those intolerant to existing therapies.
  
  
  METHODS
  Emerging therapeutic approaches to lowering LDL-C involve 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 (AMG145, REGN727 and RN316) have been tested in Phase I - III clinical trials for the treatment of hyperlipidaemia in patients at high CVD risk.
  
  
  CONCLUSIONS
  These new agents are administered subcutaneously and have been shown to have major LDL-C and apoB lowering effects either alone or in combination with statins. These novel agents are generally well tolerated and once long-term safety data are available they appear promising therapeutic platforms for the treatment of patients with hypercholesterolaemia at risk for or with CVD not controlled by conventional therapies.
authors.affiliation: University of Ioannina, School of Medicine, Department of Internal Medicine , 451 10 Ioannina , Greece.
authors.forename: Haralampos
authors.initials: H
authors.lastname: Milionis
authors.forename: George
authors.initials: G
authors.lastname: Liamis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy; D002986:Clinical Trials as Topic; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000960:Hypolipidemic Agents; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: PCSK9 inhibitors; cardiovascular disease risk; hypercholesterolaemia; lipid-lowering treatment