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.
Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels. The effect of thiophene compounds.
