title: PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia.
abstract: Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low-density lipoprotein cholesterol, as well as reductions in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long-term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid-modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia.
authors.affiliation: Sanofi US, Bridgewater, NJ, USA.|Oregon State University/Oregon Health and Science University, College of Pharmacy, Portland, OR, USA (during initial development of this article).
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Ito
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of Sao Paulo Medical School Hospital, and Preventive Medicine Center and Cardiology Program, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D019468:Disease Management; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab
keywords: alirocumab; bococizumab; evolocumab; hyperlipidemia; low-density lipoprotein cholesterol; proprotein convertase subtilisin/kexin type 9