title: AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of national cholesterol education program-adult treatment panel III low-density lipoprotein cholesterol goals among high-risk patients: an analysis from the LAPLACE-TIMI 57 trial (LDL-C assessment with PCSK9 monoclonal antibody inhibition combined with statin thErapy-thrombolysis in myocardial infarction 57).
abstract: OBJECTIVE
  This study sought to define the ability of AMG 145, a monoclonal antibody directed against proprotein convertase subtilisin kexin type 9 (PCSK9), to enable subjects at high risk for major adverse cardiovascular events to achieve National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) parameters for low-density lipoprotein cholesterol (LDL-C) and other lipid goals.
  
  
  BACKGROUND
  Many patients at high risk for adverse cardiovascular events are unable to achieve the NCEP-ATP III LDL-C goal of <70 mg/dl, even with high-potency statin therapy.
  
  
  METHODS
  In 282 subjects from the LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy-Thrombolysis In Myocardial Infarction 57) trial at high risk according to NCEP-ATP III criteria, we compared the proportion of subjects achieving the NCEP-ATP III recommended LDL-C goal of <70 mg/dl across treatment arms. Other outcomes included the triple goals of LDL-C <70 mg/dl, non-high-density lipoprotein cholesterol (HDL-C) <100 mg/dl, and apolipoprotein B (ApoB) <80 mg/dl.
  
  
  RESULTS
  During the dosing interval, more than 90% of subjects in both of the top dose groups every 2 weeks and every 4 weeks attained this lipid target over the dosing interval, with similar success rates for the triple lipid goal.
  
  
  CONCLUSIONS
  PCSK9 inhibition with AMG 145 enables high-risk patients to achieve established lipid goals. If this therapy demonstrates efficacy for reducing cardiovascular events with a favorable safety profile in ongoing phase 3 trials, we believe it will have major public health implications.
authors.affiliation: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Desai
authors.affiliation: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Division of Cardiovascular Medicine, University of California at San Francisco, San Francisco, California.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.affiliation: Amgen, Inc., Thousand Oaks, California.
authors.forename: Ransi
authors.initials: R
authors.lastname: Somaratne
authors.affiliation: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elaine
authors.initials: E
authors.lastname: Hoffman
authors.affiliation: Amgen, Inc., Thousand Oaks, California.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liu
authors.affiliation: Amgen, Inc., Thousand Oaks, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Scott
authors.affiliation: Amgen, Inc., Thousand Oaks, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: msabatine@partners.org.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010353:Patient Education as Topic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab
keywords: ApoB; CAD; CHD; CV; HDL-C; LDL; LDL-C; NCEP-ATP III; NHANES; National Cholesterol Education Program-Adult Treatment Panel III; National Health and Nutrition Examination Survey; PCSK9; UC; ULN; apolipoprotein B; cardiovascular; cholesterol; coronary artery disease; coronary heart disease; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; statins; ultracentrifugation; upper limit of normal