Abstract 9954: 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) Intake Improves Left Ventricular Ejection Fraction in Patients with Recent Acute Coronary Syndrome

Abstract

Background: Previous studies have shown coronary artery syndrome can result in left ventricular myocardial remodeling (LVMR); and progressive LVMR after infarction could lead to decline in ejection fraction. In this study we evaluated the effect of a potent and selective 5-Lipoxygenase inhibitor, VIA-2291, on Left Ventricular Ejection Fraction (LVEF) in patients with recent Acute Coronary Syndrome (ACS) on top of standard medical therapy. 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 were randomized to four study arms including: 25 mg, 50 mg, and 100 mg of VIA-2291 as well as placebo. LVEF and Stroke Volume (SV) were measured post-hoc by contrast enhanced Cardiac Computed Tomographic Angiography on GE Advantage Windows 4.4 Workstations (GE Healthcare, Milwaukee, WI). Result: There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. LVEF improved dramatically in subjects who had taken VIA-2291 vs. placebo: 1.8±8.4 vs. -3.0±9.3 (p=0.0001). Similarly SV improved significantly with VIA-2291 vs. placebo: 3.9±15.9 vs. -4.8±17.2 (p=0.0001). VIA-2291 demonstrated a dose dependent effect on LVEF and SV with largest benefit achieved with the highest dose of the drug (100mg) vs. Placebo; LVEF and SV: 2.64±6.06 and 4.65±14.01, p=0.0001, respectively (Figure 1). Of note, the placebo group was shown to have a decrease in LVEF and SV -3.1±9.3 and -4.8±17.2, respectively, which can be attributed to post-ACS myocardial-remodeling. Conclusion: The addition of VIA-2291 to standard of care medical regimen is able to improve ejection fraction dramatically in patient with recent coronary artery syndrome over a 6 month follow-up period. Benefits of VIA-2291 are dose dependent.