title: PCSK9 Inhibitors: Are We on the Verge of a Breakthrough?
abstract: Statins are first-line therapy for lowering cholesterol and reducing cardiovascular events. A significant need for new lipid-modifying therapies remains for patients unable to tolerate statins or achieve guideline-based cholesterol targets. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL receptor recycling. Gain-of-function PCSK9 mutations are associated with high low-density lipoprotein cholesterol (LDL-C) levels and increased risk of coronary artery disease, while loss-of-function variants result in low LDL-C and decreased risk of cardiovascular events. PCSK9 monoclonal antibody inhibitors have been developed and lower LDL-C levels up to 70% in clinical trials. These inhibitors are well tolerated, with low serious adverse event rates. Phase III clinical outcome trials with these agents are ongoing and will determine their efficacy in reducing cardiovascular events and address long-term safety concerns.
authors.affiliation: Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: E
authors.initials: E
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood*; D004059:Diffusion of Innovation; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000639:trends; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases