Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome

Circ Cardiovasc Imaging. 2010 May;3(3):298-307. doi: 10.1161/CIRCIMAGING.110.937169. Epub 2010 Feb 27.


Background: Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor.

Methods and results: In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (P<0.0001) in a dose-dependent fashion, with approximately 80% inhibition in >90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (P<0.01).

Conclusions: VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration- URL: Unique identifier: NCT00358826.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / diagnostic imaging
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Arachidonate 5-Lipoxygenase / drug effects
  • Arachidonate 5-Lipoxygenase / metabolism
  • Biomarkers / blood
  • Biomarkers / urine
  • C-Reactive Protein / drug effects
  • Contrast Media
  • Coronary Angiography / methods
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / therapeutic use
  • Leukotriene B4 / blood
  • Leukotriene E4 / urine
  • Lipoxygenase Inhibitors* / therapeutic use*
  • Male
  • Middle Aged
  • Observer Variation
  • Prospective Studies
  • Radiographic Image Enhancement / methods
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • Triiodobenzoic Acids


  • Biomarkers
  • Contrast Media
  • Lipoxygenase Inhibitors
  • Triiodobenzoic Acids
  • Leukotriene B4
  • Leukotriene E4
  • C-Reactive Protein
  • Arachidonate 5-Lipoxygenase
  • iodixanol
  • atreleuton
  • Hydroxyurea

Associated data