Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results

Aims Though statin therapy is known to stow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. Methods and results EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis coronary computed tomographic angiography (CCTA) (>= 1 angiographic stenoses with >= 20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age= 57 +/- 6 years, mate = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P= 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P= 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P=0.0004), fibrous plaque (17% vs. 40%, P= 0.011), and calcified plaque (-1% vs. 9%, P=0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. Conclusion EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial.

Automated summary

This study aims to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in high-risk cardiovascular patients with persistently high triglyceride levels. The interim analysis at 9 months showed that while there was no significant change in low attenuation plaque, there was a slowing of total non-calcified plaque, total plaque, fibrous plaque, and calcified plaque in the IPE group compared to placebo.