title: Targeting low-density lipoprotein cholesterol with PCSK9 inhibitors.
abstract: Over the past quarter century, clinical trials have consistently demonstrated that lowering levels of low-density lipoprotein cholesterol (LDL-C) with statins reduces the rate of major adverse cardiovascular events. However, the findings that many patients continue to experience events or harbour inappropriately high LDL-C levels despite intensive statin therapy and the clinical reality of statin intolerance suggests that additional therapeutic strategies are required in order to achieve more effective reductions in cardiovascular risk. The emergence of inhibitory monoclonal antibodies targeted against proprotein convertase subtilisin kexin type 9 (PCSK9) provides a novel approach to reducing LDL-C levels. The current experience of PCSK9 inhibitors and implications for clinical use and cost effectiveness will be reviewed.
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Scherer
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Psaltis
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Stephen J
authors.identifier: http://orcid.org/0000-0002-9668-4368
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; D016032:Randomized Controlled Trials as Topic; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: PCSK9 inhibitors; atherosclerosis; cardiovascular risk; lipids