Icosapent ethyl reduces low attenuation plaque quantity

Introduction and methods

The REDUCE-IT trial previously showed a 25% overall event reduction of the primary endpoint (CV death, MI, stroke, coronary revascularization, unstable angina) in statin-treated patients randomized to icosapent ethyl (IPE), compared with those randomized to placebo. However, the mechanism of benefit remained unknown. The aim of the EVAPORATE study was to further assess the effects of IPE on plaque progression over 9 to 18 months compared to placebo using serial CT angiography in statin-treated patients with elevated triglycerides.

EVAPORATE was a randomized, double-blind, placebo-controlled trial that randomized 80 patients on statin therapy to either treatment with IPE 4g/day (n=40) or placebo in the form of mineral oil (n=40) for 18 months. Patients were 30-85 years of age, had triglyceride levels of 135-499 mg/dl, LDL-c levels on statins >40 mg/dL and ≤115 mg/dL, ≥1 angiographic stenosis with ≥20% narrowing by CTA, and no history of CABG, MI, stenosis, or life-threatening arrhythmia within the prior 6 months. Patients underwent CT angiography at baseline, 9 months and 18 months follow-up. The primary endpoint was progression rates of low attenuation plaques. 31 patients in the IPE group and 37 patients in the placebo group completed visit 3 at 18 months follow-up.

Main results

• There were no significant differences in demographics and cardiac risk factors between the two treatment groups at baseline.
• Low attenuation plaque quantity increased from baseline to 18 months follow-up in the placebo group (change in plaque quantity: 109%) and decreased in the IPE group (change in plaque quantity: -17%). Change in plaque quantity was statistically significant between treatment groups (adjusted P value =0.0061).
• Generally, patients in the placebo group had progression of plaque quantity, while patients in the IPE group had plaque regression at 18 months follow-up compared with baseline. Significant differences between the placebo group vs. IPE group in plaque volumes were found for fibro-fatty plaque (32% vs -34%, adj. P=0.0002), fibrous plaque (1% vs. -20%, adj. P=0.0028), total non-calcified plaque (9% vs. -19%, adj. P=0.0005) and total plaque volume (11% vs. -9%, adj. P=0.0019) after multivariate adjustment. No significant difference was found between treatment groups in calcified plaque after multivariate adjustment (15% vs. -1%, adj. P=0.0531).

Conclusion

IPE 4g/day significantly reduced plaque quantity of multiple plaque components, including low attenuation plaque, compared with placebo.

-Our reporting is based on the information provided at the ESC congress -