Abstract 12548: 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) Treatment Decreases Epicardial and Pericardial Adipose Tissue in Patients with Recent Acute Coronary Syndrome

Abstract

Background: Epicardial adipose tissue (EAT) has been shown to be associated with coronary atherosclerosis and also as a predictor of future adverse cardiovascular events. VIA-2291, a selective 5-Lipoxygenase inhibitor, has been shown to have anti-inflammatory effects by reduction of leukotriene LTB4. In current study we evaluated the effect of VIA-2291 treatment on EAT and Pericardial Adipose Tissue (PAT) in patients after acute coronary syndrome (ACS)

Methods: This is a double blinded: placebo controlled: dose ranging: randomized: multicenter trial (clinicaltrials.gov NCT00358826) of 56 individuals with recent ACS who were recruited and followed for 24 weeks in an imaging substudy. Subjects with chronic liver, kidney and cardiovascular disease were excluded. Subjects on standard of care were randomized to four arms: 25 mg, 50 mg, and 100 mg of VIA-2291 and placebo. EAT and PAT were measured post-hoc by contrast enhanced Cardiac Computed Tomographic Angiography on GE Advantage Windows 4.4 Workstations (GE Healthcare, Milwaukee, WI). PAT was measured by subtracting out EAT from Intra-Thoracic Adipose Tissue (IAT) volume.

Results: There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. There was a significant decrease in EAT and PAT in patients in the treatment arms vs. placebo, -3.0±8.2 and -3.9±10.9 vs. 1.7±7.5 and 1.4±10.7 (p=0.001), respectively. The changes in EAT and PAT were dose dependent and were more pronounced in patients taking 100 mg of the drug vs. Placebo: -4.2±9.6, -7.6±8.5, p=0.0001, respectively (Figure 1).

Conclusion: After adjustment for all traditional cardiovascular risk factors, VIA-2291 decreases EAT and PAT in individuals with recent ACS. Benefits of VIA-2291 treatment are dose dependent.