Coronary Fatty Plaque Regression and Cardiac Events with EPA and DHA by Blood Pressure Status

This randomized trial enrolled 240 patients with established coronary artery disease to receive EPA+DHA supplementation or placebo, with serial CCTA measurement of coronary plaque volume as the primary endpoint. The analysis examined whether treatment benefit varied by blood pressure status and associated metabolic features.

EPA+DHA supplementation led to coronary plaque regression and fewer cardiac events specifically in normotensive patients. The treatment effect correlated with degree of triglyceride reduction and reduction in inflammatory markers. In hypertensive patients, the plaque regression effect was attenuated. The investigators attributed this to blood pressure’s independent contribution to plaque progression that omega-3 fatty acids do not adequately counter.

The treatment interaction with blood pressure control adds a clinically relevant dimension: omega-3 supplementation for plaque regression appears to work best in the metabolic context it was designed for — elevated triglycerides and inflammation — when blood pressure is simultaneously controlled. When blood pressure remains elevated, the atherogenic hemodynamic stress may override the anti-inflammatory and triglyceride-lowering effects.

The combined finding of triglyceride reduction and low non-HDL-C as correlates of plaque regression is mechanistically consistent: omega-3 fatty acids reduce triglycerides (and therefore VLDL and remnant cholesterol burden), and the plaque regression occurs through reduced atherogenic particle flux rather than a direct anti-inflammatory effect on existing plaque.

We rate the evidence moderate. A 240-patient RCT demonstrating EPA+DHA plaque regression in normotensive CAD patients, with benefit correlating to triglyceride reduction — contributing to the evidence that omega-3s’ cardiovascular benefit is metabolically context-dependent.