n–3 Fatty Acids and Cardiovascular Outcomes in Patients With Dysglycemia

Study Questions:

What is the effect of n–3 fatty acids on cardiovascular events in patients with (or at risk for) type 2 diabetes mellitus?


In this double-blind study (ORIGIN Fatty Acids trial) with a 2 x 2 factorial design, the investigators randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1 g capsule containing at least 900 mg (90% or more) of ethyl esters of n–3 fatty acids or placebo daily, and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n–3 fatty acids and placebo are reported here.


During a median follow-up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n–3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.87-1.10; p = 0.72). The use of n–3 fatty acids also had no significant effect on the rates of major vascular events (1,034 patients [16.5%] vs. 1,017 patients [16.3%]; HR, 1.01; 95% CI, 0.93-1.10; p = 0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; HR, 0.98; 95% CI, 0.89-1.07; p = 0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; HR, 1.10; 95% CI, 0.93-1.30; p = 0.26). Triglyceride levels were reduced by 14.5 mg/dl (0.16 mmol/L) more among patients receiving n–3 fatty acids than among those receiving placebo (p < 0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.


The authors concluded that daily supplementation with 1 g of n–3 fatty acids did not reduce the rate of cardiovascular outcomes in patients at high risk for cardiovascular events.


The study reports that a daily 1 g dose of n–3 fatty acids, as compared with placebo, did not prevent death or any cardiovascular outcomes in patients who had (or were at high risk for) diabetes and were at increased risk for cardiovascular events. Three other large trials (Rischio and Prevenzione study, ASCEND, and VITAL), currently underway, are assessing the use of n–3 fatty acids to prevent cardiovascular disease, and will provide additional insight on this issue. Meanwhile, these findings may support consumption of more fish, because dietary change not only increases the intake of foods containing n–3 fatty acids, but also results in a reduction in the consumption of potentially harmful foods such as red meats.

Clinical Topics: Dyslipidemia, Lipid Metabolism

Keywords: Follow-Up Studies, Fatty Acids, Cardiovascular Diseases, Diabetes Mellitus

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