From Pages to Practice

By Amanda Fernandes, MD

Published October 24, 2018


The Case

Mrs. S is a 56-year-old woman with a history of diabetes, hypertension, and depression who is seen in clinic for an annual physical examination. Her brother recently had a heart attack and she is concerned about her risk of the same. Besides her brother, she notes a strong family history of coronary heart disease. Mrs. S states that her friend recommended she take over-the-counter fish oil supplements to reduce her risk of cardiac events and asks if any evidence supports this practice.

In 1978, Dyerberg and colleagues linked low rates of coronary heart disease in the Greenland Inuit population to the omega-3 fatty acids form the cold-water fish in their diet. Since then, both observational and randomized studies have tested this hypothesis with conflicting results. The American Heart Association currently recommends omega-3 fatty acid supplementation for secondary prevention of heart disease. As the pendulum has swung in different directions, omega-3 fatty acid supplementation has become a booming industry valued at $27 billion in 2016.

The Study

In last week’s issue of NEJM, the ASCEND (A Study of Cardiovascular Events in Diabetes) trial compared the efficacy and safety of daily supplementation with omega-3 fatty acids or placebo in patients with diabetes mellitus (any type) and no known cardiovascular disease. Researchers randomized 15,480 patients in the United Kingdom to receive either 1 gram of omega-3 fatty acid (460 mg of eicosapentanoic acid and 380 mg of docosahexaenoic acid) or placebo (olive oil). Using a factorial design in the same trial, patients were also randomly assigned to receive daily aspirin (100 mg) or placebo, with results reported separately. Blood and urine samples were obtained from participants after 2.5 years. Adverse events were monitored with follow-up questionnaires every 6 months.

The primary outcome was a first serious vascular event, which included nonfatal myocardial infarction or stroke, transient ischemic attack, or vascular death. The secondary outcome was a first serious vascular event or any arterial revascularization.

Following a mean follow-up of 7.4 years, the frequency of serious vascular events did not differ significantly between the omega-3 fatty acid and placebo groups (8.9% vs. 9.2%) nor did the frequency of serious vascular events or any arterial vascularization (11% in both groups).

The Conclusion

Returning to the case of Mrs. S, this study suggests that omega-3 fatty acids would not reduce her risk of developing serious vascular events. The question of whether the lack of effect is dose-related remains to be answered in ongoing trials.

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Amanda Fernandes is a 2018-2019 NEJM editorial fellow.