Background: Although omega-3 fatty acid supplements may be effective for the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Observational studies have reported a beneficial effect with fish or fish oil consumption, whereas randomized controlled trials (RCTs) have yielded mixed results. A 2009 meta-analysis of 11 RCTs (including studies without placebo control groups) reported that omega-3 fatty acid supplement use had a protective effect against CVD, although an earlier systematic review of RCTs found no clear benefit. Kwak and colleagues conducted a meta-analysis of randomized, double-blind, placebo-controlled trials to determine whether the two major omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), could help prevent cardiovascular events among patients with CVD.

The Study: RCTs were included in the analysis if the participants had used omega-3 fatty acid supplementation for a minimum of one year and if the study reported specific cardiovascular outcomes, including angina, myocardial infarction, heart failure, stroke, and cardiovascular and all-cause mortality. The primary analysis was the association between supplementation and overall cardiovascular events.

Results: Fourteen trials including 20,485 patients were reviewed. The mean age of participants was 63.4 years (range = 40 to 80 years), the mean EPA or DHA dosage was 1.7 g per day (range = 0.4 to 4.8 g per day), and the mean follow-up period was two years (range = 1.0 to 4.7 years). Overall, omega-3 fatty acid supplementation was not found to reduce the risk of overall cardiovascular events (relative risk [RR] = 0.99; 95% confidence interval [CI], 0.89 to 1.09). Similarly, no significant protective effect was found in most other outcome measures, including all-cause mortality, sudden cardiac death, fatal or nonfatal myocardial infarction, angina, congestive heart failure, and transient ischemic attack and stroke. Subgroup analyses found no significant protective effect against CVD based on the duration of treatment (less than two years versus two years or more) or the dosage of EPA or DHA (less than 1.7 g per day versus 1.7 g or more per day). A small significant protective effect was found with omega-3 fatty acid supplementation in reducing cardiovascular death (RR = 0.91; 95% CI, 0.84 to 0.99) and in a subgroup analysis of CVD prevention among patients using anti-platelet agents (RR = 0.71; 95% CI, 0.5 to 1.0); however, these associations disappeared after excluding one study with major methodologic problems.

Conclusion: In this meta-analysis of placebo-controlled RCTs, there was insufficient evidence of a cardiovascular benefit from omega-3 fatty acid supplementation among patients with preexisting CVD.