title: Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease.
abstract: OBJECTIVE
  To investigate the effects of secretory phospholipase A2 (sPLA(2)) inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote atherosclerosis by mechanisms that include lipoprotein modification, retention, and oxidation.
  
  
  RESULTS
  Phospholipase Levels And Serological Markers of Atherosclerosis II (PLASMA II) is a Phase II, randomized, double-blind, placebo-controlled parallel-arm study of two once-daily doses of the novel sPLA(2) inhibitor, 1-H-indole-3-glyoxamide or varespladib methyl (Anthera Pharmaceuticals, Hayward, CA, USA). One hundred and thirty-five stable coronary heart disease patients were treated with either varespladib methyl 250 mg once daily, varespladib methyl 500 mg once daily, or placebo for 8 weeks. Varespladib methyl treatment resulted in statistically significant dose-dependent reductions that were different from placebo in sPLA(2) concentration, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL) cholesterol. When compared with placebo, varespladib methyl 500 mg once daily reduced LDL cholesterol by 15% (P < 0.001), non-HDL cholesterol by 15% (P < 0.001), total very LDL (VLDL) particle concentration by 14% (P = 0.022), and small VLDL particle concentration by 24% (P = 0.030). Relative to baseline, varespladib methyl 500 mg once daily reduced total LDL particle concentration (7%, P = 0.002) and small LDL particle concentration (11%, P = 0.014).
  
  
  CONCLUSIONS
  Reductions in atherogenic lipoproteins suggest that varespladib methyl 500 mg once daily may be an effective anti-atherosclerotic agent. Trial registered at ClinicalTrials.gov, identifier: NCT00525954.
authors.affiliation: Mount Sinai Heart-Box 1030, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. robert.rosenson@mssm.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.forename: Yuri
authors.initials: Y
authors.lastname: Stasiv
authors.forename: Colin
authors.initials: C
authors.lastname: Hislop
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000368:Aged; D001055:Apolipoproteins B / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage*; D007651:Keto Acids; D008297:Male; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000085:Acetates; D001055:Apolipoproteins B; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D007651:Keto Acids; D014280:Triglycerides; C545088:varespladib methyl; D002097:C-Reactive Protein; D002784:Cholesterol; D054497:Phospholipases A2, Secretory