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

JC Tardif, PL L'allier, R Ibrahim… - Circulation …, 2010 - Am Heart Assoc
JC Tardif, PL L'allier, R Ibrahim, JC Grégoire, A Nozza, M Cossette, S Kouz, MA Lavoie…
Circulation: Cardiovascular Imaging, 2010Am Heart Assoc
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 …
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.
Am Heart Assoc