Meta-Analysis Finds No CV Benefit of Omega-3 Fatty Acids

September 13, 2012

September 13, 2012 (Ioannina, Greece) — A new meta-analysis looking at the effects of omega-3 fatty acids in patients at high risk for cardiovascular events has shown that the supplements have no effect on hard clinical outcomes, including all-cause mortality, cardiac death, sudden death, MI, or stroke [1]. There was a trend toward benefit in the prevention of sudden death, but the reduction failed to reach statistical significance, a finding the researchers believe refutes any supposed antiarrhythmic-mediated effect of omega-3 fatty acids.

"The meta-analysis, taking into account the recent and previously published trials, showed that omega-3 fatty acids did not significantly reduce the incidence of cardiovascular events," senior investigator Dr Moses Elisaf (University Hospital of Ioannina, Greece) told heartwire . "However, there was a trend toward benefit in terms of sudden death, about a 13% reduction, and myocardial infarction, about a 10% reduction, but the decrease was not statistically significant. So, we can conclude from this meta-analysis and other recently published trials that the effect of omega-3 fatty-acid supplementation in high-risk patients is rather low. They are without side effects, but without significant efficacy."

The study is published in the September 12, 2012 issue of the Journal of the American Medical Association.

Some clinical guidelines, including those of the European Society of Cardiology (ESC), recommend omega-3 polyunsaturated fats, either through supplements or dietary changes, after MI. Despite the recommendations, there is a large degree of controversy and uncertainty regarding the benefits of omega-3 polyunsaturated fats on the risk of major cardiovascular events. Currently, the US Food and Drug Administration (FDA) has approved high-dose omega-3 fatty acids for the treatment of high triglyceride levels in patients with overt hypertriglyceridemia.

Speaking with heartwire , Elisaf said few trials included in the meta-analysis used the high-dose omega-3 fatty-acid supplements, that being 2 to 4 g per day as approved by the FDA, so more studies are needed to study the benefit of using the high-dose supplements to lower triglyceride levels and prevent cardiovascular events. "We need more data to clearly define the role of omega-3 fatty acids in clinical practice," said Elisaf.

Efficacy of Omega-3 Fatty Acids Across Clinical Outcomes


Relative risk (95% CI)

All-cause mortality

0.96 (0.91–1.02)

Cardiac death

0.91 (0.85–0.98)*

Sudden death

0.87 (0.75–1.01)


0.89 (0.76–1.04)


1.05 (0.93–1.18)

*Reduction in cardiac death events not significant after corrected for multiple comparisons

The meta-analysis included 20 clinical trials of 68 680 patients. Some of the studies were published as early as 1989, but more than half of the clinical trials were published when statins were routinely recommended for the reducing the risk of cardiovascular disease. The mean omega-3 dose used in the trial was 1.5 g/day, or 0.77 g/day eicosapentaenoic acid (EPA) and 0.60 g/day docosahexaenoic acid (DHA). The median treatment duration was two years, and the maximum was 6.2 years.

Given the negative results, Elisaf said that one of the reasons can be explained by contemporary treatment of patients at high risk for cardiovascular disease. One of the pivotal trials that first suggested omega-3 fatty acids could reduce the risk of cardiovascular disease, GISSI, was undertaken before patients were regularly treated with other cardiovascular medications, including cholesterol-lowering agents. "Today, our high-risk patients take aspirin and statins," he said. "So, we have patients with much lower levels of LDL cholesterol, and the potential benefits of reducing mortality further with other agents, including omega-3 fatty acids, might be marginal."

While many patients might take omega-3 fatty acids over the counter, Elisaf said the present trial included only doses and formulations recommended by FDA and other medical authorities around the world. Low-dose formulations purchased over the counter were not included in the analysis. Elisaf noted that the meta-analysis included clinical trials with varying methodologies and clinical hypotheses, as well as different prevention settings, in order to provide a big-picture assessment of the evidence.