Vascular healing response associated with adjunctive n‐3 polyunsaturated fatty acid therapy in patients receiving strong statin therapy remains unclear. This study aimed to evaluate the effect of polyunsaturated fatty acid therapy with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in addition to strong statin therapy on coronary atherosclerotic plaques using optical coherence tomography.

This prospective multicenter randomized controlled trial included 130 patients with acute coronary syndrome (ACS) treated with strong statins. They were assigned to either statin only (control group, n=42), statin+high‐dose EPA (1800 mg/day) (EPA group, n=40), statin+EPA (930 mg/day)+DHA (750 mg/day) (EPA+DHA group, n=48). Optical coherence tomography was performed at baseline and the 8‐month follow‐up. The target for optical coherence tomography analysis was a non-culprit lesion with a lipid plaque. There were no significant differences in the percent change for minimum FCT between the EPA or EPA+DHA group and the control group. In patients with FCT <120 µm, the percent change for minimum FCT was significantly greater in the EPA or EPA+DHA group than the control group.

In conclusion, this study of patients with ACS, EPA or EPA+DHA therapy in addition to strong statin therapy did not significantly increase FCT in non-culprit plaques compared with strong statin therapy alone but significantly increased FCT in patients with thinner FCT. EPA or EPA+DHA therapy, in addition to strong statin therapy, might provide a more significant stabilizing effect on coronary plaques with vulnerable features.