Abstract

Background: Despite the beneficial effects of statins on progression of coronary atherosclerosis and cardiovascular (CV) events, significant CV risk persists in patients with hypertriglyceridemia. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) added to statins reduced initial and total CV events by 25% and 30%, but the mechanisms of benefit are unclear. In a follow-up analysis, degree of CV benefit from IPE was predominantly related to achieved serum EPA levels. Methods: EVAPORATE is a randomized, placebo-controlled trial, using CCTA to evaluate the effects of IPE as an adjunct to statins on coronary plaque volumes in a cohort with elevated triglycerides. Here, we present the 18-month, pre-specified secondary end-point analysis on association of achieved serum EPA levels, and change in coronary plaque volumes in the pooled cohort. Results: 80 patients were enrolled, and 68 completed the 18-month visit. Median (IQR) level of serum EPA for the pooled cohort was 20.6 (13.8) ug/ml at baseline and 25.3 (55.5) ug/ml at follow up. At 18 months, EPA levels > 26 ug/ml predicted regression of fibro-fatty plaque (logβ: - 0.75± 0.36), total non-calcified plaque (TNCP) (logβ: - 0.77± 0.33), and total plaque (TP) (logβ: - 0.63± 0.28) volumes (mm3), after adjustment for age, sex, diabetes, hypertension, and baseline TGL levels (p < 0.05 for all). Conclusions: Higher serum EPA levels predict regression of prognostically relevant coronary plaque volumes, TNCP, and TP on CCTA. This provides important mechanistic correlation to the CV benefits of IPE.

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