In a systematic review and meta-analysis of 38 randomized controlled trials comprising 149,051 participants, omega-3 fatty acids — such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids — were associated with reducing cardiovascular mortality and other cardiovascular outcomes; the cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.
“The effects of omega-3 fatty acids, such as EPA and DHA acids, on cardiovascular outcomes are uncertain,” said Dr. Deepak Bhatt, a researcher at Brigham and Women’s Hospital Heart and Vascular Center, and his colleagues.
“We aimed to determine the effectiveness of omega-3 fatty acids on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects.”
The researchers performed a comprehensive literature search, without language restriction, using the electronic databases of EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library, as well as web-sites of major cardiovascular and medicine journals, through June 7, 2021.
They reviewed a total of 798 articles for eligibility after removing duplicates and screening at the title and abstract level. Further, 760 articles were removed based on a priori study selection criteria.
Ultimately, 38 trials encompassing 149,051 adult participants were included. The patients’ mean age ranged from 39 to 78 years. The median follow-up duration across the trials was two years.
Four trials compared EPA vs. control and 34 trials compared EPA+DHA vs. control. Twenty-two trials studied primary prevention.
The dose of omega-3 fatty acids ranged from 0.4 g/day to 5.5 g/day. The EPA trials had dose ranges from 1.8 to 4.0 g/day and EPA+DHA from 0.4 to 5.5 g/day.
The scientists evaluated key cardiovascular outcomes, including cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation.
Overall, they found that omega-3 fatty acids improved cardiovascular outcomes.
Trials of EPA showed higher relative reductions in cardiovascular outcomes than those of EPA+DHA, with significant interaction terms.
“There are crucial biological differences between EPA and DHA — while both are considered omega-3 fatty acids, they have different chemical properties that influence their stability and strength of the effect that they can have on cholesterol molecules and cell membranes,” the authors said.
No trials to date have studied the effects of DHA alone on cardiovascular outcomes.
“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA,” Dr. Bhatt said.
“It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings.”
The team’s results were published in the journal eClinical Medicine.
Safi U. Khan et al. Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. eClinical Medicine, published online July 8, 2021; doi: 10.1016/j.eclinm.2021.100997
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