A phase 2 randomized, double-blind, placebo-controlled study of the effect of VIA-2291, a 5-lipoxygenase inhibitor, on vascular inflammation in patients after an acute coronary syndrome. Issue 1 (May 2015)

• Record Type: Journal Article
• Authors: Gaztanaga, Juan; Farkouh, Michael; Rudd, James H.F.; Brotz, Tilmann M.; Rosenbaum, David; Mani, Venkatesh; Kerwin, Todd C.; Taub, Rebecca; Tardif, Jean-Claude; Tawakol, Ahmed; Fayad, Zahi A.
• Is Part Of: Atherosclerosis. Volume 240:Issue 1(2015)
• Page Start: 53
• Page End: 60
• Publication Date: 2015-05
• Subjects: Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.02.027
• Languages: English
• ISSNs: 0021-9150

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Objective</title> <p id="abspara0010">Arachidonate 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes. VIA-2291 is a potent 5-LO inhibitor, which has been shown to reduce hsCRP and noncalcified coronary plaque volume following an acute coronary syndrome (ACS). We aim to evaluate the effect of VIA-2291 on vascular inflammation compared to placebo using FDG-PET.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">A Phase II, randomized, double-blind, parallel-group study was conducted in 52 patients with recent ACS assigned 1:1 to either 100 mg VIA-2291 or placebo for 24 weeks. The primary outcome was the effect of VIA-2291 relative to placebo on arterial inflammation detected by <sup>18</sup>fluorodeoxyglucose positron emission tomography (FDG-PET) within the index vessel after 24 weeks of daily treatment, compared to baseline.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">VIA-2291 was relatively well tolerated and was associated with a significant inhibition of the potent chemo-attractant LTB4, with a mean inhibition of activity of 92.8% (p < 0.0001) at 6 weeks in the VIA-2291 group, without further significant change in inhibition at 24 weeks. However, for VIA-2291 was not associated with significant difference in inflammation (target-to-background ratio) compared to placebo at 24 weeks or 6 weeks of treatment. Further, VIA-2291 was not associated with a significant reduction in hsCRP from baseline after either 6 or 24 weeks of treatment.</p> </sec> <sec> <title id="sectitle0030">Conclusions</title> <p id="abspara0025">VIA-2291 is well-tolerated and effectively reduces leukotriene production. However, inhibition of 5-LO with VIA-2291 is not associated with significant reductions in vascular inflammation (by FDG-PET) or in blood inflammatory markers. Accordingly, this study does not provide evidence to support a significant anti-inflammatory effect of VIA-2291 in patients with recent ACS.</p> </sec> </abstract>