Eicosapentaenoic Acid Therapy Is Associated with Decreased Coronary Plaque Instability Assessed Using Optical Frequency Domain Imaging

This retrospective study used optical frequency domain imaging (OFDI) — a high-resolution intracoronary imaging technique — to examine whether eicosapentaenoic acid (EPA) therapy altered the composition of coronary plaques in patients undergoing percutaneous coronary intervention.

In 60 patients, EPA was associated with decreased lipid index, lower macrophage grade, and increased fibrous cap thickness — all markers of a shift from vulnerable (thin-capped, lipid-rich) to more stable (thick-capped, fibrous) plaque morphology. This structural change is the mechanistic basis thought to underlie the cardiovascular benefit of high-dose omega-3 fatty acids observed in the REDUCE-IT trial.

The limitation is the retrospective design with modest sample size. OFDI captures plaque morphology but not clinical outcomes, and confounding by indication — EPA-treated patients may differ in unobserved ways from non-treated patients — is difficult to exclude without randomization.

We rate the evidence limited. Biologically coherent imaging data supporting EPA-mediated plaque stabilization, but insufficient to establish clinical benefit independently of the randomized trial evidence that motivated this line of inquiry.