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)?

Methods:

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).

Results:

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).

Conclusions:

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.

Perspective:

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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