Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-Analysis
What is the effect of omega-3 fatty acid supplementation on major cardiovascular outcomes?
A systematic review and meta-analysis was conducted using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. Criteria for inclusion included randomized controlled clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. Subgroup analyses were performed for the presence of blinding, and whether primary or secondary prevention. Meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of 0.0063 was assumed after adjustment for multiple comparisons.
Of the 3,635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7,044 deaths, 3,993 cardiac deaths, 1,150 sudden deaths, 1,837 myocardial infarctions, and 1,490 strokes. No statistically significant association was observed with all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke when all supplement studies were considered.
Overall, omega-3 polyunsaturated fatty acid supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.
Among the known and putative benefits of dietary and supplemental omega-3 PUFAs include their ability to lower triglyceride levels (at the expense of raising low-density lipoprotein cholesterol), prevent atrial fibrillation and sudden death, decrease platelet aggregation, lower blood pressure, reduce depression, and improve cognitive function. The inability to demonstrate a clear benefit despite the large clinical trials is similar to the anti-oxidant vitamin supplements. Despite the attempts to neutralize differences in study designs, a neutral meta-analysis does not establish lack of benefit, albeit it blunts the enthusiasm. Among the concerns drawing conclusions from this report are that of the 20 studies included, only eight had 3 or more years of follow-up and four included primary and secondary prevention. Would anyone accept this design in a statin or antiplatelet trial?
Keywords: Myocardial Infarction, Stroke, Death, Fatty Acids, Cardiovascular Diseases, MEDLINE
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