A Randomized Controlled Trial of Eicosapentaenoic Acid in Patients With Coronary Heart Disease on Statins: The CHERRY Study

The CHERRY (CHolEsteRol lowering by pitavastatin and eicosapentaenoic acid in patients with coronary artERY disease) trial randomized 193 patients with coronary heart disease on high-dose pitavastatin to add EPA supplementation or no addition, measuring coronary plaque volume and composition by IVUS at 12 months.

Combination EPA plus pitavastatin therapy significantly reduced total coronary plaque volume and lipid-rich plaque content compared with pitavastatin monotherapy, particularly in patients with stable angina. The plaque regression effect was greater in patients with lower baseline EPA/AA ratios — consistent with a dose-response relationship between omega-3 repletion and plaque benefit.

The CHERRY trial adds to a body of Japanese RCT evidence (including JELIS, PROSPECTIVE, and CHERRY itself) showing that EPA supplementation modifies coronary plaque composition. The potential mechanisms include triglyceride lowering, anti-inflammatory effects through EPA-derived specialized pro-resolving mediators (SPMs), and direct membrane incorporation effects on plaque cells.

The translational context: while Japanese EPA trials have generally shown positive plaque and event signals, the REDUCE-IT trial (high-dose icosapentaenoic acid [EPA], 4g/day) showed a 25% MACE reduction in a Western population, though the mineral oil comparator’s lipid-raising effects complicated interpretation. STRENGTH (corn oil comparator) showed no benefit with omega-3 at equivalent dose.

We rate the evidence moderate. An IVUS trial demonstrating that EPA added to statin therapy reduces coronary plaque volume and lipid content in CHD patients — mechanistically consistent with plaque-stabilizing effects but relying on surrogate imaging endpoints rather than cardiovascular events.