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

Abstract

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-blind study, 191 patients were randomized 3 weeks after an acute coronary syndrome (ACS) to receive 25, 50, or 100 mg VIA-2291 or placebo qd for 12 weeks. The primary study endpoint, 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 non-compliant, and 28 had non-evaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo and 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in non-calcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this endpoint was analyzable (P<0.01).

Conclusions—VIA-2291 reduces leukotriene production at 12 weeks after an ACS. 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— http://data.linkedct.org/resource/trials/NCT00358826; ClinicalTrials.gov Identifier: NCT00358826