Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on coronary plaque progression: a serial CT angiography study.

Background: Inflammation has a key role in the process of atherosclerosis. Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic plaques and cardiovascular events.

Hypothesis: In this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA).

Methods: Patients with recent acute coronary syndrome (ACS) were prospectively assigned to one of 3 VIA-2291 doses (25 mg, 50 mg, 100 mg) or placebo by oral administration. All groups underwent CCTA at baseline and at 6 months' follow-up. Plaque types such as low-attenuation plaque (LAP), fibro-fatty tissue (FF), fibro-calcified plaque (FC), and dense calcium plaque (DC) were measured based upon predefined density threshold, and changes from baseline CCTA were analyzed.

Results: The final analysis included 54 patients (age, 56 ± 9 years; 85.1% male) with CCTA at baseline and 24 weeks. Evaluating on treatment VIA-2291 (all 3 doses, n = 37) demonstrated significant reductions in plaque progression compared with placebo (n = 17). VIA-2291 significantly reduced LAP (5.9 ± 20.7 mm vs -9.7 ± 33.3 mm ), FF (11.1 mm  ± 13.3 mm vs -0.9 ± 2.7 mm ), and FC (-0.1 ± 6.22 mm vs -14.3 ± 6.2 mm ; all P < 0.05) and retarded the progression of DC (3.9 ± 3.2 mm vs 0.2 ± 0.4 mm ) compared with placebo.

Conclusions: VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS (http://ClinicalTrials.gov NCT00358826).