Omega-3 FA Supplements May Only Modestly Impact High-Risk Populations from CVD

A recent meta-analysis concluded that marine-derived omega-3 fatty acids had no significant association with fatal or non-fatal coronary heart disease or other major vascular events, providing no support for current recommendations for the use of these supplements in those with a history of coronary heart disease.

While the results were not statistically significant, the findings did identify the potential for a 7% lower risk of major vascular events and a 10% lower risk of coronary heart disease associated with the use of the supplements — validating the nutritional interventions as having subtle effects.

“[The meta-analysis] Provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease,” study authors wrote.

Current omega-3 fatty acid supplement guidelines advocate for the use of 1 g/d of omega-3 fatty acid supplements in prevention of coronary heart disease and major vascular events in those with prior coronary heart disease, however large trials have produced differing results.

The meta-analysis, assessing associations of omega-3 fatty acids with the risk of vascular risks, included randomized trials that involved a sample size of at least 500 participants and a treatment duration of at least 1 year. All eligible trials required the use of supplements, but no minimum dose of the omega-3 fatty acids.

Aggregated study-level data were obtained from 10 clinical trials involving 77,917 participants demonstrating the use of the supplements for a mean of 4.4 years. Of the participants, 47,803 (61.4%) were men, and the mean age at entry was 64 years.

The prespecified end points included nonfatal myocardial infarction; death caused by coronary heart disease; ischemic, hemorrhagic and unclassified stroke; coronary or noncoronary arterial revascularization events; major vascular events; and all-cause mortality.

Combinations of polyunsaturated fatty acid ethyl esters of eicosapentaenoic acid (EA) and docosahexanoic acid (DHA) were used in all besides 1 trial, in which tested a daily dose of 1800 mg EPA alone. The daily doses of EPA varied from 226 to 1800 mg/day, while DHA varied from 0 to 1700 mg/day.

Of the participants, about two-thirds of patients had a prior history of coronary heart disease (31,076 of 46,767, or 66.4%); 13,240 of 47,938 had stroke (28%) and 28,722 of the total participants had prior diabetes (37%).

During the study duration, there were a total of 12,001 major vascular events (15.4% of the total participants) including 2276 incidents of nonfatal myocardial infarction; 2695 coronary heart disease deaths (3.5%), 1713 strokes (2.2%0 and 6603 revascularization events (8.5%).

The omega-3 fatty acid supplementation was not significantly associated with the rate ratios for any coronary heart disease event (RR: 0.96; 95%CI: 0.90-1.01; P=0.12), coronary heart disease death (RR: 0.93; 99%CI: 0.83-1.03; P=0.05), non-fatal myocardial infarction (RR: 0.97; 99%CI: 0.87-1.08; P=0.40), major vascular events (RR: 0.97; 95%CI: 0.93—1.01; P=0.10), stroke (RR: 1.03; 95%CI: 0.93-1.13; P=0.56), revascularization events (RR: 0.99; 95%CI: 0.94-1.04; P=0.61), all-cause mortality (RR: 0.96; 95%CI: 0.92-1.01; P=0.16).

“This meta-analysis also showed no significant heterogeneity between the results of individual trials for nonfatal MI, CHD death, any CHD events or all major vascular events,” study authors added.

Similar results were found after adjustment for multiple testing, where the supplements had no significant association with major vascular events in any of the prespecified subgroups, including those defined by gender, history of coronary heart disease, history of diabetes, pretreatment levels of total cholesterol, high-density lipoprotein levels, low density lipoprotein levels, triglyceride levels or prior statin therapy use.

The meta-analysis data does not support the recommendation of 1 g/d of omega-3 fatty acid supplements in those with a history of coronary heart disease for the prevention of fatal coronary heart disease, nonfatal myocardial infarction or other vascular events.

The results from ongoing trials are needed to asses if higher doses of the supplements like 3—4 g/d may have significant effects.

The meta-analysis, "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks" was published in JAMA Cardiology January 2018.

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