Icosapent ethyl improves coronary hemodynamics
Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRct
Introduction and methods
In the REDUCE-IT trial, icosapent ethyl (IPE) reduced the risk of ischemic events compared with placebo in statin-treated patients with CVD or DM and elevated triglyceride levels [1-4]. The mechanisms behind this clinical benefit, however, are not fully known. Although the EVAPORATE (Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy) trial showed that IPE decreased plaque burden as measured by coronary computed tomography angiography (CTA) , the impact of IPE on coronary physiology has not been studied.
Aim of the study
The authors examined the impact of IPE compared with placebo on coronary hemodynamics as assessed by fractional flow reserve derived from coronary CTA (FFRct) using imaging data from the EVAPORATE trial.
The EVAPORATE trial was a multicenter, double-blind, placebo-controlled RCT conducted in the USA in which 80 patients with coronary atherosclerosis and persistently elevated triglyceride levels were randomized to IPE 4 g/day or placebo, as an adjunct to diet and statin therapy. Plaque volume progression rates were evaluated with coronary CTA at baseline, 9 months, and 18 months. In the current analysis, data from 47 patients (22 in IPE group vs. 25 in placebo group) with interpretable coronary CTA scans for FFRct analysis at baseline and during follow-up were included, yielding a total of 507 coronary lesions.
The prespecified primary endpoint was the FFRct value in the distal coronary segment of the most diseased vessel at baseline and during follow-up per patient. The prespecified secondary endpoint was the change in translesional FFRct across the most severe coronary lesion (diameter stenosis ≥30%) per vessel. Translesional FFRct was defined as difference in FFRct values between the proximal and distal points.
- At baseline, mean (± SD) FFRct was similar for patients taking IPE and those on placebo (0.83 ± 0.08 vs. 0.84 ± 0.08; P=0.55).
- A significant improvement in the primary endpoint (distal segment FFRct) was observed in the IPE group compared with the placebo group at 9 months (0.01 ± 0.05 vs. –0.05 ± 0.09; difference: 0.06; 95%CI: 0.01–0.11; P=0.02) and 18 months (–0.01 ± 0.09 vs. –0.09 ± 0.12; difference: 0.08; 95%CI: 0.01–0.15; P=0.03).
- The mean (± SD) translesional FFRct across the most severe coronary lesion per vessel (n=140) showed an improvement for IPE versus placebo, although the difference was not statistically significant (–0.06 ± 0.08 vs. –0.09 ± 0.1; difference: 0.0298; 95%CI: –0.0006 to 0.0601; P=0.054).
In this analysis of the EVAPORATE trial, IPE showed beneficial effects on coronary physiology compared with placebo as indicated by an improvement in distal segment FFRCT at 9-month follow-up, which was sustained at 18-month follow-up. According to the authors, this “provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial.” This analysis is also “the first assessment of FFRct to determine drug effect.”