Introduction: Early clinical trials of omega-3 fatty acids (FAs) conducted prior to the wide use of statins showed benefit on cardiovascular events whereas more recent trials have shown variable results. The effect of statin intensity and omega-3 FA supplementation on plaque progression is not clear
Hypothesis: Omega-3 FAs prevent coronary plaque progression in subjects on low-intensity statins but not in subjects on high-intensity statins.
Methods: 291 subjects with stable coronary artery disease and on statins were randomized to high-dose omega-3 FA (1.86 g of EPA and 1.5 g of DHA daily) or no omega-3 FA (control) for 30 months. Type and dose of statin were recorded. Coronary computed tomographic angiography was used to measure plaque volume (mm3) indexed by segment length of fatty, fibrous, non-calcified and calcified plaque. The analysis was intention-to-treat. Results were stratified by intensity of statin therapy.
Results: Of those on low-intensity statin, controls had significant progression of fibrous plaque volume whereas those receiving high-dose omega-3 FAs had no change (median % change [IQR], 4.8 [-5.1, 19.0] vs 0.3 [-12.8, 9.0], respectively; P=0.032) (Table). Similar changes were noted on noncalcified plaque with a trend toward significance (P=0.062). In contrast, in the high-intensity statin group, no difference in plaque change was observed in either treatment arm. These findings occurred with mean low-density-lipoprotein cholesterol levels ≤80.5 mg/dL and median triglyceride levels <125 mg/dL in both treatment arms.
Conclusion: High-dose statin therapy masked a beneficial effect of omega-3 FAs on coronary plaque progression compared to low-intensity statins where controls had progression of plaque compared to no change in the omega-3 FA group. Future studies should examine whether intensity of statin therapy affects outcome in omega-3 FA trials.