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J Am Coll Cardiol. 2014 Apr 8;63(13):1278-88. doi: 10.1016/j.jacc.2014.01.006. Epub 2014 Feb 5.

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.

Author information

  • 1Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
  • 2TIMI Study Group, Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  • 3Jacksonville Center For Clinical Research, Jacksonville, Florida.
  • 4Lipid Clinic, Oslo University Hospital, Oslo, Norway.
  • 5Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky.
  • 6Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • 7Karolinska University Hospital, Stockholm, Sweden.
  • 8Amgen Inc., Thousand Oaks, California.
  • 9EVLIN Consultants, Chicago, Illinois. Electronic address:



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.


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.


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.


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.


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.

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


PCSK9 inhibition; dyslipidemia; evolocumab; lipoprotein(a)

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