Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction.
OBJECTIVE
Recent secondary prevention trials have failed to demonstrate a beneficial effect of n-3 fatty acids on cardiovascular outcomes, which may be due to the growing use of statins since the mid-1990s. The aim of the present study was to assess whether statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI).


RESULTS
Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3740) and consistent statin non-users (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 (HR(adj)). Among the statin users 495 (13%) and among the statin non-users 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events [HR(adj) 1.02; 95% confidence interval (CI): 0.80, 1.31; P = 0.88]. In statin non-users, however, only 9% of those who received EPA-DHA plus ALA experienced an event compared with 18% in the placebo group (HR(adj) 0.46; 95% CI: 0.21, 1.01; P= 0.051).


CONCLUSIONS
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.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Simone R B M
SR
Eussen
Johanna M
JM
Geleijnse
Erik J
EJ
Giltay
Cathy J M
CJ
Rompelberg
Olaf H
OH
Klungel
Daan
D
Kromhout
D000368:Aged; D000369:Aged, 80 and over; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004347:Drug Interactions; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006323:Heart Arrest / Q000401:mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008383:Margarine; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D020521:Stroke / Q000401:mortality
D002317:Cardiovascular Agents; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008383:Margarine