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

BackgroundInflammation has a key role in the process of atherosclerosis. Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic plaques and cardiovascular events. HypothesisIn this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA). MethodsPatients with recent acute coronary syndrome (ACS) were prospectively assigned to one of 3 VIA-2291 doses (25mg, 50mg, 100mg) 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. ResultsThe final analysis included 54 patients (age, 569years; 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 +/- 20.7mm(3) vs -9.7 +/- 33.3mm(3)), FF (11.1mm(3)+/- 13.3mm(3) vs -0.9 +/- 2.7mm(3)), and FC (-0.1 +/- 6.22mm(3) vs -14.3 +/- 6.2mm(3); all P < 0.05) and retarded the progression of DC (3.9 +/- 3.2mm(3) vs 0.2 +/- 0.4mm(3)) compared with placebo. Conclusions VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS ( NCT00358826).