Abstract 15389: Effect of Icosapent Ethyl on Changes in Coronary Plaque Characteristics at 9 Months in Patients With Elevated Triglycerides on Statin Therapy: Insights From EVAPORATE

Abstract

Background: Residual cardiovascular (CV) risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total CV events by 30%, but the mechanisms of benefit are not fully understood. The EVAPORATE trial evaluated the effects of IPE as adjunct to statins on adverse atherosclerotic plaque characteristics by CCTA. Here we use a novel software validated using histology to evaluate the effect of IPE on vulnerable plaque features. Methods: The EVAPORATE trial randomized statin-treated patients, with high TG (135-499 mg/dL), and known atherosclerosis to IPE 4 g/d or placebo. Plaque characteristics including lipid rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH) were assessed using vascuCAP ® (Elucid Bioimaging Inc., Boston, MA). Per-patient multivariable models robust with respect to physiological variation were used to evaluate plaque progression. Results: A total of 60 patients had interpretable images. Relative to placebo, patients on IPE demonstrated decreased wall volume (-7.2 vs. +28.4 mm 3 ), LRNC (-1.4 vs. +9.7 mm 3 ), and IPH (-0.02 vs. +0.3 mm 3 ), as well as increased cap thickness (+100 vs. -290 microns), indicating a migration to more stable phenotypes (p>0.05).Statistical significance was achieved when incorporated into an optimized neural network model of lipid-rich phenotype (p = 0.04), AUROC=0.7[0.63,0.77], sensitivity=0.66[0.59,0.74], specificity=0.64 [0.56,0.72], and Cohen’s kappa=0.3 [0.19,0.41]. Operating points when used as a per-patient measure of response are presented in Figure 1. Conclusions: This study demonstrated that IPE, when added to statin therapy, is associated with reduction in vulnerable plaque, moving patients to a more stable plaque phenotype.