Statin Use Mitigate the Benefit of Omega-3 Fatty Acids Supplementation—A Meta-Regression of Randomized Trials

During last 2 decades, multiple studies have evaluated omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation for cardiovascular prevention. The benefit found in previous studies was not demonstrated in more contemporary trials. We aimed to investigate effect of study characteristics, particularly concomitant statin therapy on results of randomized controlled trials. We systematically searched electronic databases for randomized controlled trials evaluating ω-3 PUFA supplementation and reporting clinical outcomes. A meta-analysis was performed using a random effect model, followed by a meta-regression of dose, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio, and duration of treatment and use of lipid-lowering/statin therapy in control group. Twenty-three studies with 77,776 patients (38,910 PUFA; 38,866 controls) were included. PUFA had no effect on total mortality [risk ratio (RR) = 0.96; 95% confidence interval (CI), 0.92-1.01] and myocardial infarction (RR = 0.87; 95% CI, 0.73-1.02), but marginally reduced cardiovascular mortality (RR = 0.93; 95% CI, 0.87-0.98). Lower control group statin use (b = 0.222, P = 0.027) and higher DHA/EPA (b = -0.105, P = 0.033) ratio was associated with higher reduction in total mortality. Duration and dose had no effect. None of the variables except duration had significant effect on reduction in cardiovascular mortality by PUFA supplementation. There was evidence of publication bias. Statin use may mitigate, and higher DHA/EPA ratio is associated with the beneficial effect of PUFA supplementation.