title: PCSK9 inhibitors: monoclonal antibodies for the treatment of hypercholesterolemia.
abstract: In 2015 the U.S. Food and Drug Administration approved the first two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab (Praluent®; Sanofi/ Regeneron) and evolocumab (Repatha®; Amgen), for use in patients with heterozygous and homozygous familial hypercholesterolemia and for patients intolerant of statins or those with a major risk of cardiovascular disease (CVD) but unable to lower their LDL cholesterol (LDL-C) to optimal levels with statins and ezetimibe. Numerous randomized clinical trials have demonstrated that these inhibitors cause a fall in LDL-C levels of 50-60% as well as causing a decline in lipoprotein(a) and an increase in HDL cholesterol. They are effective in reducing levels of LDL-C to 1.8 mmol/L or less in almost all patients in the groups listed above except for those with homozygous familial hypercholesterolemia. In the latter case, many patients will still have LDL-C levels well above optimal levels despite the use of statins and a PCSK9 inhibitor. To date these inhibitors have not caused major adverse effects. However, the results of ongoing long-term randomized clinical trials are needed to determine whether they cause a significant reduction in CVD events including deaths from CVD. These studies will also demonstrate whether the PCSK9 inhibitors have any unexpected adverse effects and/or effects resulting from the loss of PCSK9 functions at other sites in the body, in particular regarding neurocognition. A further major concern is the high cost of PCSK9 inhibitors and their effect on healthcare costs and health insurance premiums.
authors.affiliation: Emeritus Professor of Pharmacology, University of Auckland, Auckland, New Zealand. dmpaton38@yahoo.ca.
authors.forename: D M
authors.initials: DM
authors.lastname: Paton
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab
keywords: Alirocumab; Evolocumab; Familial hypercholesterolemia; Hypercholesterolemia; PCSK9; Proprotein convertase subtilisin/kexin type 9; Statin intolerance