title: Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study.
abstract: BACKGROUND
  Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels.
  
  
  OBJECTIVE
  To determine the effects of evolocumab on vitamin E and steroid hormone levels.
  
  
  RESULTS
  After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L.
  
  
  CONCLUSIONS
  As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01516879.
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.). dirk.blom@uct.ac.za.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Blom
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: C Stephen
authors.initials: CS
authors.lastname: Djedjos
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Monsalvo
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: Ian
authors.initials: I
authors.lastname: Bridges
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: Rob
authors.initials: R
authors.lastname: Scott
authors.affiliation: From the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Cardiovascular Therapeutic Area, Amgen Inc, Thousand Oaks, CA (C.S.D., M.L.M., S.M.W., R.S.); Biostatistics-International, Amgen Ltd, Uxbridge, United Kingdom (I.B.); and President, Sterling Research Group, Cincinnati, OH (E.R.).
authors.forename: Eli
authors.initials: E
authors.lastname: Roth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014810:Vitamin E / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D012739:Gonadal Steroid Hormones; D014810:Vitamin E; D000324:Adrenocorticotropic Hormone; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; D006854:Hydrocortisone
keywords: PCSK9 protein; adrenal steroid hormones; cardiovascular disease; gonadal hormones; low-density lipoprotein cholesterol; risk factors; vitamin E