title: Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on coronary plaque progression: a serial CT angiography study.
abstract: BACKGROUND
  Inflammation has a key role in the process of atherosclerosis. Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic plaques and cardiovascular events.
  
  
  OBJECTIVE
  In this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA).
  
  
  METHODS
  Patients with recent acute coronary syndrome (ACS) were prospectively assigned to one of 3 VIA-2291 doses (25 mg, 50 mg, 100 mg) or placebo by oral administration. All groups underwent CCTA at baseline and at 6 months' follow-up. Plaque types such as low-attenuation plaque (LAP), fibro-fatty tissue (FF), fibro-calcified plaque (FC), and dense calcium plaque (DC) were measured based upon predefined density threshold, and changes from baseline CCTA were analyzed.
  
  
  RESULTS
  The final analysis included 54 patients (age, 56 ± 9 years; 85.1% male) with CCTA at baseline and 24 weeks. Evaluating on treatment VIA-2291 (all 3 doses, n = 37) demonstrated significant reductions in plaque progression compared with placebo (n = 17). VIA-2291 significantly reduced LAP (5.9 ± 20.7 mm3vs -9.7 ± 33.3 mm3), FF (11.1 mm3± 13.3 mm3vs -0.9 ± 2.7 mm3), and FC (-0.1 ± 6.22 mm3vs -14.3 ± 6.2 mm3; all P < 0.05) and retarded the progression of DC (3.9 ± 3.2 mm3vs 0.2 ± 0.4 mm3) compared with placebo.
  
  
  CONCLUSIONS
  VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS (http://ClinicalTrials.gov NCT00358826).
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Suguru
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Montréal Heart Institute, Montréal, Canada.
authors.forename: Reda
authors.initials: R
authors.lastname: Ibrahim
authors.affiliation: Montréal Heart Institute, Montréal, Canada.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Grégoire
authors.affiliation: Montréal Heart Institute, Montréal, Canada.
authors.forename: Philippe L
authors.initials: PL
authors.lastname: L'Allier
authors.affiliation: Montréal Heart Institute, Montréal, Canada.
authors.forename: Josephine
authors.initials: J
authors.lastname: Pressacco
authors.affiliation: Montréal Heart Institute, Montréal, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072226:Computed Tomography Angiography / Q000379:methods*; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage; D008875:Middle Aged; D061330:Multidetector Computed Tomography / Q000379:methods*; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016859:Lipoxygenase Inhibitors; C096921:atreleuton; D006918:Hydroxyurea
keywords: Clinical trials; Imaging; Ischemic heart disease; acute coronary syndromes; computed tomography