ACS Trial
This study was designed to establish dose and safety data in patients with acute coronary syndrome (ACS) who have experienced a recent heart attack, and included measures of leukotrienes, biomarkers of inflammation as well as medical imaging of the coronary vessel wall to evaluate impact on plaque characteristics. Data from the ACS trial was first reported at the November 2008 AHA 2008 Scientific Sessions, and the MDCT serial imaging results were reported in a poster presentation at the ATVB meeting in May, 2009.
Results
A publication describing these results was published in Circulation, Cardiovascular Imaging.
Circ. Cardiovasc. Imaging 2010;3:298-307
Abstract of Publication
Treatment With 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) in Patients With Recent Acute Coronary Syndrome
Jean-Claude Tardif1; Philippe L. L’Allier1; Reda Ibrahim1; Jean C. Grégoire1; Anna Nozza2; Mariève Cossette2; Simon Kouz3; Marc-André Lavoie1; Janie Paquin1; Tilmann M. Brotz4; Rebecca Taub4 and Josephine Pressacco1
1 Montreal Heart Institute and Université de Montréal, Montreal, Canada; 2 Montreal Heart Institute Coordinating Center, Montreal, Canada; 3 Centre Hospitalier Régional de Lanaudière, Joliette, Canada; 4 VIA Pharmaceuticals, Princeton, NJ
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: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.