Effects of N-3 Fatty Acids on Major Cardiovascular Events in Statin Users and Non-Users With a History of Myocardial Infarction

Study Questions:

Do statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI)?


Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3,740) and consistent statin nonusers (n = 413). In these two groups of patients, the effects of an additional daily amount of 400 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), 2 g α-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Cox’s proportional hazard models were used to calculate adjusted hazard rate ratios (HRadj).


Among the statin users, 495 (13%) and among the statin nonusers 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events (HRadj, 1.02; 95% confidence interval [CI], 0.80-1.31; p = 0.88). In statin nonusers, however, only 9% of those who received EPA–DHA plus ALA experienced an event compared with 18% in the placebo group (HRadj 0.46; 95% CI, 0.21-1.01; p = 0.051).


The authors concluded that in patients with a history of MI who are not treated with statins, low-dose supplementation with n-3 fatty acids may reduce major cardiovascular events.


This study suggests that statin treatment modifies the effects of n-3 fatty acids on the incidence of major cardiovascular events. In statin users, additional n-3 fatty acids had no effect on major cardiovascular events, but in statin nonusers, reductions in major cardiovascular events due to EPA–DHA alone or ALA alone were 18% and 10%, respectively. The combined effects of EPA–DHA plus ALA accumulated to a robust 54% reduction in adverse events. These results may explain the inconsistent results on the effects of n-3 fatty acids in secondary prevention trials. Consistent with current guidelines, post-MI patients should ideally be treated with statins, but for the subset of patients who do not tolerate statins, supplementation with n-3 fatty acids may be an alternative to reduce their risk of future cardiovascular events.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Myocardial Infarction, Dietary Supplements, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatty Acids

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