title: Development of proprotein convertase subtilisin/kexin type 9 inhibitors and the clinical potential of monoclonal antibodies in the management of lipid disorders.
abstract: The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of published long-term ODYSSEY and OSLER studies are summarized. There have been three excellent meta-analysis studies on PCSK9 inhibitors which are outlined. The complex problem of cost-effectiveness was carefully evaluated by the Institute for Clinical and Economic Review (ICER). The draft report (ICER-2015) is summarized herewith. The cardiovascular outcome trials with Evolocumab (FOURIER), Alirocumab (ODYSSEY OUTCOME) and Bococizumab (SPIRE-1 and SPIRE-2) are the ongoing clinical trials, and their results are expected in 2017-2018. The search for new cost-effective analogs of PCSK9 inhibitors is ongoing.
authors.affiliation: Department of Interventional Cardiology, Santokba Durlabhji Memorial Hospital Cum Medical Research Institute, Jaipur, India.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000960:Hypolipidemic Agents; D008055:Lipids; D000091362:PCSK9 Inhibitors; D015842:Serine Proteinase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: ASCVD; LDLc; PCSK9