Background: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of EPA and DHA in the secondary prevention of CVD.
Methods: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials.
Results: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of EPA or DHA, or use of fish oil supplementation only as treatment.
Authors' Conclusion: 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.
O-3s & Secondary Prevention of CVD
Kwak SM Myung SK Lee YJ and Seo HG for the Korean Meta-analysis Study Group (published online April 9, 2012). Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. doi:10.1001/archinternmed.2012.262.
The totality of the publicly available scientific evidence demonstrates a cardiovascular benefit of EPA and DHA in healthy populations, as well as in the majority of populations with pre-existing cardiovascular ailments.
The already long list of long-chain omega-3 recommendations from professional organizations and government bodies continues to grow because the science is so compelling.
What Else Should You Know?
The investigators included only placebo-controlled trials which eliminated some of the best studies, including DART (1), JELIS (4) and GISSI Prevenzione Trial (3), all three of which were strongly positive for cardiovascular endpoints.
The study design was the reason many of the studies included in the present meta-analysis failed to demonstrate a benefit
o Population characteristics
o Not designed to evaluate CVD end points
o Underpowered--not a failure to demonstrate an effect; rather a failure to detect an effect
o Subjects in more recent trials received better treatment with statins, antithrombotics and antihypertensive medications than those in earlier trials. Of the 14 studies included in the meta-analysis, GOED reviewed 10 of the associated publications and found that every one of the studies included subjects on at least one medication.
It has been estimated that low n-3 polyunsaturated fatty acid intakes account for 72,000-96,000 deaths per year from CVD in the United States alone (2).
Global Organization for EPA and DHA Omega-3s (2012). Omega-3s & Secondary Prevention of CVD [Peer commentary on the paper “Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo-controlled trials” by Kwak SM Myung SK Lee YJ and Seo HG for the Korean Meta-analysis Study Group (published online April 9, 2012). Arch Intern Med. doi:10.1001/archinternmed.2012.262.].
(1) Burr ML Fehily AM Gilbert JF Rogers S Holliday RM Sweetnam PM Elwood PC and Deadman NM (1989). Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 2(8666):757-761.
(2) Danaei G Ding EL Mozaffarian D Taylor B Rehm J Murray CJ and Ezzati M (2009). The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6: e1000058.
(3) Gissi-HF Investigators Tavazzi L Maggioni AP Marchioli R Marchioli R Barlera S Franzosi MG Latini R Lucci D Nicolosi GL Porcu M Tognoni G (2008). Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 372(9645):1223-1230.
(4) Yokoyama M Origasa H Matsuzaki M Matsuzawa Y Saito Y Ishikawa Y Oikawa S Sasaki J Hishida H Itakura H Kita T Kitabatake A Nakaya N Sakata T Shimada K Shirato K; Japan EPA Lipid Intervention Study (JELIS) Investigators (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients ( JELIS): a randomised openlabel, blinded endpoint analysis. Lancet. 369(9567):1090-1098.