Amarin’s Vascepa Studies Assess Coronary Physiology and Plaque Progression

May 12, 2023—Amarin Corporation plc announced new data describing the benefits of Vascepa/Vazkepa (icosapent ethyl) on coronary physiology and plaque progression.

The EVAPORATE-FFR_CT study on the benefit of icosapent ethyl on coronary physiology assessed by CTA fractional flow reserve (FFR) was published by Mark G. Rabbat, MD, et al in European Heart Journal—Cardiovascular Imaging. Dr. Rabbat, the study’s lead author, is Professor of Medicine and Radiology and Director of Cardiac CT at Loyola University in Chicago, Illinois.

The plaque progression study, “Effect of Icosapent Ethyl on In Vivo Atheroma Progression and Inflammatory Protease Activity,” was presented by Mohamad Kassab, MD, at the American Heart Association’s Vascular Discovery 2023 meeting held May 10-13 in Boston, Massachusetts.

The objective of the EVAPORATE-FFR_CT study was to assess the impact of Vascepa/Vazkepa on coronary physiology assessed by FFR derived from coronary CTA data sets (FFR_CT) using imaging data from the EVAPORATE trial.

The EVAPORATE trial assessed the efficacy of Vascepa/Vazkepa in reducing plaque burden among patients on stable statin therapy with known angiographic coronary artery disease (CAD). The trial demonstrated that in statin-treated patients, Vascepa/Vazkepa significantly reduced plaque burden measured by serial coronary CTA compared with placebo.

According to Amarin, EVAPORATE-FFR_CT study is the first assessment of FFR_CT to determine drug effect. The study showed there was significant improvement in the prespecified primary endpoint of FFR_CT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using Vascepa/Vazkepa compared with placebo. Vascepa/Vazkepa improved mean distal segment FFR_CT at 9- and 18-month follow-up compared with placebo (P = .02 and P = .03 respectively).

The secondary endpoint of change in translesional FFR_CT (Δ FFR_CT across the most severe [minimum 30%] diameter stenosis) coronary lesion per vessel was improved with Vascepa/Vazkepa treatment compared with placebo, although it was not statistically significant (P = .054).

Dr. Rabbat commented in Amarin’s press release, “The early and sustained improvement in FFR_CT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial, which demonstrated that Vascepa/Vazkepa significantly reduced ischemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. Additionally, as this is the first assessment of FFR_CT to determine drug effect, it has potentially important implications in utilizing FFR_CT to predict treatment response.”

The plaque progression study conducted in animals found that Vascepa/Vazkepa reduced in vivo plaque progression versus control (P = .03) as measured by intravascular ultrasound and plaque cathepsin protease activity (P = .005) measured by near-infrared fluorescence molecular imaging.

On fluorescence microscopy, plaques from animals treated with Vascepa/Vazkepa exhibited fewer macrophages (P = .04).

Farouc Jaffer, MD, who is Director of the Massachusetts General Hospital Coronary Intervention and Chronic Total Occlusion PCI Program in Boston, Massachusetts, commented in the press release, “This study—which shows that Vascepa/Vazkepa reduces in vivo plaque progression, plaque cathepsin protease activity, and plaque macrophages—provides novel experimental evidence supporting the anti-atherosclerosis and anti-inflammatory effects of the medication. However, in vivo mechanisms underlying these effects remain somewhat unclear.”