title: Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials.
abstract: OBJECTIVE
  The purpose of this study was assess the effect of evolocumab (AMG 145) on lipoprotein (Lp)(a) from a pooled analysis of 4 phase II trials.
  
  
  BACKGROUND
  Lp(a), a low-density lipoprotein (LDL) particle linked to the plasminogen-like glycoprotein apolipoprotein(a), shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies. Current therapeutic options to reduce Lp(a) are limited.
  
  
  METHODS
  A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy. Lp(a) was measured using a standardized isoform-independent method.
  
  
  RESULTS
  Evolocumab treatment for 12 weeks resulted in significant (p < 0.001) mean (95% confidence interval) dose-related reductions in Lp(a) compared to control: 29.5% (23.3% to 35.7%) and 24.5% (20.4% to 28.7%) with 140 mg and 420 mg, dosed every 2 and 4 weeks, respectively, with no plateau of effect. Lp(a) reductions were significantly correlated with percentages of reductions in LDL-C (Spearman correlation coefficient, 0.5134; p < 0.001) and apolipoprotein B (Spearman correlation coefficient, 0.5203; p < 0. 001). Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins.
  
  
  CONCLUSIONS
  Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of ≤125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nmol/l.
authors: Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors: Frederick J
authors: FJ
authors: Raal
authors: TIMI Study Group, Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Robert P
authors: RP
authors: Giugliano
authors: TIMI Study Group, Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Marc S
authors: MS
authors: Sabatine
authors: Jacksonville Center For Clinical Research, Jacksonville, Florida.
authors: Michael J
authors: MJ
authors: Koren
authors: Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors: Gisle
authors: G
authors: Langslet
authors: Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky.
authors: Harold
authors: H
authors: Bays
authors: Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Dirk
authors: D
authors: Blom
authors: Karolinska University Hospital, Stockholm, Sweden.
authors: Mats
authors: M
authors: Eriksson
authors: Amgen Inc., Thousand Oaks, California.
authors: Ricardo
authors: R
authors: Dent
authors: Amgen Inc., Thousand Oaks, California.
authors: Scott M
authors: SM
authors: Wasserman
authors: Amgen Inc., Thousand Oaks, California.
authors: Fannie
authors: F
authors: Huang
authors: Amgen Inc., Thousand Oaks, California.
authors: Allen
authors: A
authors: Xue
authors: Amgen Inc., Thousand Oaks, California.
authors: Moetaz
authors: M
authors: Albizem
authors: Amgen Inc., Thousand Oaks, California.
authors: Rob
authors: R
authors: Scott
authors: EVLIN Consultants, Chicago, Illinois. Electronic address: esteinmrl@aol.com.
authors: Evan A
authors: EA
authors: Stein
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001055:Apolipoproteins B / Q000097:blood; D017209:Apoptosis; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood; D016896:Treatment Outcome; D014461:Ultracentrifugation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab
keywords: PCSK9 inhibition; dyslipidemia; evolocumab; lipoprotein(a)