title: PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy.
abstract: Atherosclerosis is characterized by cholesterol deposition in the arterial intima, with subsequent plaque formation and arterial disease. Low-density lipoprotein cholesterol (LDL-C) plays the most important role in the atherogenesis process, which is the substrate of cardiovascular disease and is the leading cause of death worldwide. Several studies show that a strict control of risk factors, particularly the reduction of LDL-C levels, is a cornerstone in primary and secondary prevention of coronary heart disease. Statins are currently the most effective drugs for lowering LDL-C, but the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has opened up new therapeutic options in lipid management. PCSK9 reduces LDL-receptors' recycling resulting in a decrease of LDL-C receptors on the surface of hepatocytes and an increase of LDL-C levels in plasma. Obviously, inhibition of PCSK9 has been associated with an increase of LDL-C receptors with subsequent lowering of plasma levels of LDL-C. The clinical development of monoclonal antibodies against PCSK9 has been achieved through phase I and II studies, and nowadays there are many ongoing phase III trials with promising preliminary results. The aim of this review is to update the evidence for PCSK9 monoclonal antibodies, such as evolocumab, alirocumab and bococizumab, in LDL-C management and to discuss their therapeutic perspectives based on the most recent clinical studies, with attention to side-effects.
authors: Cardiocentro Ticino, Lugano, Switzerland.
authors: Andrea
authors: A
authors: Denegri
authors: Iveta
authors: I
authors: Petrova-Slater
authors: Elena
authors: E
authors: Pasotti
authors: Maria Grazia
authors: MG
authors: Rossi
authors: Giovanni Battista
authors: GB
authors: Pedrazzini
authors: Tiziano
authors: T
authors: Moccetti
authors: Marco
authors: M
authors: Moccetti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C000598888:bococizumab; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab