Treatment With 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) in Patients With Recent Acute Coronary Syndrome

• Published in: Circulation. Cardiovascular imaging Vol. 3; no. 3; pp. 298 - 307
• Main Authors: TARDIF, Jean-Claude, L'ALLIER, Philippe L, TAUB, Rebecca, PRESSACCO, Josephine, IBRAHIM, Reda, GREGOIRE, Jean C, NOZZA, Anna, COSSETTE, Mariève, KOUZ, Simon, LAVOIE, Marc-André, PAQUIN, Janie, BROTZ, Tilmann M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-05-2010
• Subjects: 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; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Biomarkers - urine; Blood and lymphatic vessels; C-Reactive Protein - drug effects; Cardiology. Vascular system; Contrast Media; Coronary Angiography - methods; Coronary heart disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart; Humans; Hydroxyurea - analogs & derivatives; Hydroxyurea - therapeutic use; Leukotriene B4 - blood; Leukotriene E4 - urine; Lipoxygenase Inhibitors - therapeutic use; Male; Medical sciences; Middle Aged; Myocarditis. Cardiomyopathies; Observer Variation; Prospective Studies; Radiographic Image Enhancement - methods; Tomography, X-Ray Computed - methods; Treatment Outcome; Triiodobenzoic Acids; Human; Enzyme; Cardiovascular disease; Patient; Inflammation; Myocardial disease; Coronary heart disease; imaging; leukotrienes; Vascular disease; Leukotriene; coronary disease; Treatment; Atherosclerosis; Oxidoreductases; Lipoxygenase; Acute coronary syndrome
• ISSN: 1941-9651; 1942-0080
• DOI: 10.1161/CIRCIMAGING.110.937169

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.
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).
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: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.