Reduced progression of coronary atherosclerosis with icosapent ethyl

The EVAPORATE trial showed that icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, significantly reduced multiple plaque components over 18 months, including a significant regression of low-attenuation plaque volume on multidetector computed tomography (MDCT) [1,2].

Although statins reduce cardiovascular (CV) events and slow progression of coronary atherosclerosis, significant CV risk remains. The REDUCE-IT trial previously showed that the addition of icosapent ethyl to statin therapy reduced initial CV events by 25% and total CV events by 32% [3]. However, the mechanisms of this benefit are not yet fully explained. The EVAPORATE trial set out to further assess the effects of icosapent ethyl plaque volume, measured by serial MDCT, compared with placebo [2].

Icosapent ethyl versus placebo

The randomised, double-blind, placebo-controlled EVAPORATE trial, presented by Prof. Matthew Budoff (Harbor-UCLA Medical Center, USA), enrolled 80 patients with manifest coronary atherosclerosis, as documented by MDCT (≥1 angiographic stenoses with ≥20% narrowing). Participants had to be on statin therapy and have persistently elevated triglyceride levels. The median triglyceride level was 259.1 mg/dL.

In the placebo group, low-attenuation plaque volume more than doubled from baseline to 18 months follow-up (increase in plaque quantity: 109%) and decreased in the icosapent ethyl group (reduction in plaque quantity: 17%). Change in plaque quantity was statistically significant between treatment groups (P=0.0061).

Plaque progression versus regression

While patients in the placebo group had a progression of plaque quantity, patients in the icosapent ethyl group showed reduced plaque at 18 months follow-up compared with baseline. In addition, significant differences were observed in rates of progression between icosapent ethyl and placebo at follow-up of 18 months, including:

• 
  
  • 
    
    • fibrofatty plaque: +32% versus -34% (P=0.0002);
    • fibrous plaque: +1% versus -20% (P=0.0028);
    • total non-calcified plaque: +9% versus -19% (P=0.0005); and
    • total plaque volume: +11% versus -9% (P=0.0019), respectively.

Only dense calcium did not show a significant difference between groups after multivariate adjustment (15% vs -1%; P=0.053).

 

1. 
   
   1. Budoff M. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy. ESC 2020 E-Congress, Lipids session 29 Aug.
   2. Budoff MJ, et al. Eur Heart J. 2020, 29 August.
   3. Bhatt DL, et al. N Engl J Med 2019; 380:11-22.

Posted on 5 November 202027 March 2024