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Editor's Correspondence
Oct 8, 2012

The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil Trials

Author Affiliations

Author Affiliations: Department of Pharmacy, Wegmans, Ithaca, New York (Dr DiNicolantonio); University of Missouri–Kansas City School of Medicine, Kansas City (Dr O’Keefe); and Department of Cardiology, Ochsner Medical Center, New Orleans, Louisiana (Dr Lavie).

Arch Intern Med. 2012;172(18):1427-1428. doi:10.1001/archinternmed.2012.3755

Kwak et al1(p686) state that “Our meta-analysis showed 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.” We respectfully disagree with this conclusion. This meta-analysis mainly included trials comprising only 50 to 550 patients with just 2 years or less of follow-up (the point at which the survival curves started to diverge in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico [GISSI] Heart Failure study2) in 10 of the 14 trials. In addition, 5 of the 14 trials were, in fact, not truly placebo controlled but used olive oil as a comparator. Kromhout et al3 used omega-3 fatty acids in margarine spread over multiple pieces of toast per day, which could nullify any beneficial effects of fish oil. Most included trials were not powered to detect a difference in cardiovascular outcomes (OMEGA4 and the SU.FOL.OM3 [Supplémentation en Folates et Omega-3]5 studies had approximately 20% power to detect a 25% benefit of omega-3 and the Alpha Omega study3 [used just 380 mg/d of eicosapentanoic acid + docosahexaenoic acid] had approximately half the statistical power as the GISSI-Prevenzione study6). Thus, a “lack of inclusion of sufficient trial data” should not be interpreted as “insufficient evidence at preventing cardiovascular events.”