Omega-3 fatty acid supplements failed to show a benefit for secondary prevention of cardiovascular disease (CVD), authors of a meta-analysis concluded.

Data from 14 randomized trials showed a relative risk of 0.99 for patients treated with omega-3 supplements, virtually identical to the risk in the placebo groups.

A small reduction in cardiovascular death disappeared after exclusion of a trial that had major methodologic problems, investigators reported online in Archives of Internal Medicine.

“Our results show 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,” Seung-Kwon Myung, MD, of the National Cancer Center in Ilsan, South Korea, and co-authors concluded in their article.

The findings are at odds with analyses performed before 2010, which showed a significant benefit for secondary prevention, the authors added.

However, the results are consistent with those of the most recent clinical trials, which generally have shown no effect of omega-3 supplements for prevention of cardiovascular events in patients with existing CVD.

A series of articles published in the 1970s made a case for consumption of fish or marine mammals rich in omega-3 fatty acids as the explanation for the low prevalence of CVD among Eskimos living in Greenland.

Subsequent clinical and preclinical investigations supported the epidemiologic evidence by suggesting that omega-3 fatty acids have anti-inflammatory, anti-atherogenic, and anti-arrhythmic effects, the authors wrote in their introduction.

Continued research yielded inconsistent or conflicting results about the effects of omega-3 fatty acids on cardiovascular risk. A systematic review and meta-analysis showed an overall benefit of omega-3 intake on primary and secondary cardiovascular prevention (Am J Clin Nutr 2006; 84: 5-17).

Data from randomized trials, most of which focused on secondary prevention, have remained controversial, owing to inconsistent results and methodologic problems of some studies, the authors continued. Moreover, no meta-analyses have included results of clinical trials published since 2010.

Myung and colleagues performed a comprehensive review and meta-analysis that incorporated the most recent data on the effects of omega-3 supplementation on secondary cardiovascular prevention.

From 1,007 published articles reviewed, they selected 14 randomized, double-blind, placebo-controlled trials for the analysis. The trials involved a total of 20,485 patients with a history of CVD. In all of the trials, patients used omega-3 supplements for at least a year.

The primary analysis focused on the association between omega-3 fatty acid supplementation and total cardiovascular events.

The overall lack of benefit extended to all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, and stroke or transient ischemic attack.

The only benefit identified by the analysis was a 9% reduction in the relative risk of cardiovascular death. After exclusion of a large clinical trial that had methodologic problems, the benefit disappeared.

An extensive subgroup analysis failed to identify any patients who benefited from omega-3 fatty acid supplementation.

Despite the resoundingly negative results, authors of an accompanying editorial left the door open to the possibility of a cardiovascular benefit from omega-3 fatty acid supplementation.

Specifically, they cited the need to await results from an ongoing 20,000-patient randomized trial of vitamin D and omega-3 supplementation for primary prevention. They also suggested a course of action for physicians until the trial results come in.

“To date, there is no conclusive evidence to recommend fish oil supplementation for primary or secondary prevention of CVD,” Frank B. Hu, MD, PhD, and JoAnn E. Manson, MD, DrPH, of Harvard and Brigham and Women’s Hospital in Boston, wrote in their summation.

“However, a diet high in fatty fish ... 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.”

Patients who cannot or will not eat fish should consider increasing consumption of plant-derived omega-3 fatty acids, they suggested.

“For primary or secondary prevention, omega-3 supplementation cannot supersede an overall healthy diet, but a cardioprotective diet needs to be rich in omega-3 fatty acids,” Hu and Manson concluded.

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Primary source: Archives of Internal Medicine
Source reference: Kwak SM, et al “Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease.” Arch Intern Med 2012; DOI:10.1001/archinternmed.2012.262.

Additional source: Archives of Internal Medicine
Source reference: Hu FB, Manson JE “Omega-3 fatty acids and secondary prevention of cardiovascular disease — Is it just a fish tale?” Arch Intern Med 2012; DOI:10.1001/archinternmed.2012.463.