Analysis Suggests Insufficient Evidence that Omega-3 Fatty Acid Supplements Offer Secondary Prevention of Cardiovascular Events in Patients with Heart Disease



An analysis of prior clinical trials suggests there is insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease, according to a report published Online First in Archives of Internal Medicine, a JAMA Network publication1.

Although some previous clinical trials have reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive, the study background indicates.

Sang Mi Kwak, M.D., of the Center for Cancer Prevention and Detection, Republic of Korea, and colleagues conducted a meta-analysis to examine the association between use of the omega-3 fatty acid supplements eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and risk of CVD among patients with existing CVD.

Their analysis included 14 randomized, double-blind, placebo-controlled trials that involved 20,485 patients with a history of CVD. The mean (average) age of participants was 63.4 years old and 78.5 percent of the participants were men. Among the trials, reported from June 1995 through November 2010, the daily dose of EPA or DHA ranged from 0.4 to 4.8 g/d (grams per day) and follow-up ranged from one to 4.7 years.

“Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events,” the authors note. “Likewise, we found no beneficial effect of omega-3 fatty acid supplements on other cardiovascular events, such as sudden cardiac death, myocardial infarction (fatal or nonfatal heart attack), angina and unstable angina, congestive heart failure, and transient ischemic attack and stroke, or on all-cause mortality.”

In an invited commentary2, Frank B. Hu, M.D., Ph.D., of the Harvard School of Public Health, Boston, and JoAnn E. Manson, M.D., Dr.P.H., of Brigham and Women’s Hospital, Boston, write: “The inconsistent results from secondary prevention trials set the stage for the meta-analysis by the Korean Meta-analysis Study Group reported in this issue of Archives. … Several aspects of this meta-analysis need to be carefully considered. Among 14 RCTs [randomized clinical trials] included in the meta-analysis, most were very small short-term studies and were not designed to evaluate CVD end points.”

“While waiting for more definitive results, what should physicians tell their patients? To date, there is no conclusive evidence to recommend fish oil supplementation for primary or secondary prevention of CVD. However, a diet high in fatty fish (≥2 servings of marine fish per week) should continue to be recommended for the general population and for patients with existing CVD because fish not only provides omega-3 fatty acids but also may replace less healthy protein sources, such as red meat,” they conclude.


1. (Arch Intern Med. Published online April 9, 2012. doi:10.1001/archinternmed.2012.262.

2. (Arch Intern Med. Published online April 9, 2012. doi:10.1001/archinternmed.2012.463.