Cardiovascular occasion discount from omega-3 fish oils as a consequence of EPA not DHA

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The cardiovascular benefits of omega-3 fish oils are well documented, but an updated analysis suggests that this is due to EPA rather than DHA. is due

The omega-3 fish oils eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to reduce adverse cardiovascular events, at least from some studies, although the evidence is not yet conclusive. The alleged mechanisms by which omega-3 fish oils could reduce cardiovascular events include the ability to lower triglycerides, their cell membrane stabilizing effects along with collective antithrombotic, anti-inflammatory and antiarrhythmic effects. However, studies published in 2018 gave different results; the ASCEND study showed no benefit in diabetics without cardiovascular disease. In contrast, the REDUCE-IT study found a 25 percent reduction in the primary composite efficacy endpoint of cardiovascular death, non-fatal MI, stroke, and coronary revascularization with a high-purity form of EPA in patients with established cardiovascular disease. In fact, other evidence shows that EPA alone resulted in a 19% reduction in serious coronary events in patients with hypercholesterolemia.

Given this possible heterogeneity in the two omega-3 fish oils, a team from the Department of Medicine at West Virginia University, USA, performed a meta-analysis of the effects of omega-3 fatty acids on cardiovascular outcomes. The team only included adult randomized controlled trials comparing omega-3 fish oil (EPA or EPA and DHA) intake with placebo, trials with a follow-up of at least 12 months, and where cardiovascular outcomes of interest were recorded. There were a number of specified endpoints including cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, and hemorrhagic stroke. The safety endpoints included atrial fibrillation (AF), major and minor bleeding.

Results
A total of 38 studies with 149,051 patients were included in the final analysis. There were 4 studies using EPA alone, with the rest comparing both omega-3 fish oils to placebo and 22 studies that focused on primary prevention. The dose of omega-3 fish oils ranged from 0.4 g / day to 5.5 g / day and the median follow-up time in the studies was 2 years. Overall, the use of EPA and DHA was associated with a small but statistically significant reduction in cardiovascular mortality (relative risk, RR = 0.93, 95% CL 0.88-0.98, p = 0.01), but not the overall mortality (RR = 0.97, 95% CL 0.93-1.02, p = 0.27). Interestingly, using EPA alone resulted in a greater reduction in cardiovascular mortality than the combination of the two (RR = 0.82 vs. 0.94, EPA alone vs. EPA & DHA). Here, too, monotherapy with EPA showed a higher risk reduction in non-fatal MI (RR = 0.72 vs. 0.92, EPA alone vs. EPA & DHA). Despite these additional benefits, EPA use alone resulted in a higher risk of total bleeding (RR = 1.49) and the development of AF (RR = 1.35), although the authors indicated that the safety of this evidence was lower Quality.

They concluded that although the available evidence shows that the omega-3 fish oils are linked to small but significant cardiovascular benefits, EPA use alone appears to have a slight benefit, however, further research is warranted to investigate this observed effect in more detail.

Quote
Khan SU et al. Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis. Eclinical Med 2021

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