Network meta-analysis observes no clear effect of eicosapentaenoic acid on CV outcomes

Eicosapentaenoic acid (EPA) displayed cardiovascular benefits over mineral oil but not compared with other placebo oils or standard-of-care. Moreover, the applicability of mineral oil as a placebo oil is questionable. Thus, the benefits of EPA supplementation are not conclusive.

Dr Yujiro Yokoyama (St. Luke’s University Health Network, PA, USA) explained that most randomised clinical trials evaluating the effect of omega-3 fatty acid supplementation on cardiovascular risk reduction have shown neutral results [1]. Although a recent trial did show benefits of an EPA supplement in the secondary prevention of cardiovascular events, the suitability of the used placebo oil is a topic of discussion [2,3]. A network meta-analysis was conducted to examine the effect of EPA, docosahexaenoic acid (DHA), or EPA plus DHA on cardiovascular death, myocardial infarction, stroke, coronary revascularisation, and all-cause death. In total, 17 randomised controlled trials investigating 141,009 participants were included in the analysis.

In reducing cardiovascular death, the findings showed that EPA was more effective than mineral oil in (HR 0.80) in 1 analysis: a regimen of EPA plus DHA showed superiority in the prevention of cardiovascular death compared with olive oil (HR 0.93) and controls (HR 0.83). EPA versus placebo demonstrated neutral results in 6 other comparisons.

In reducing myocardial infarction, EPA was overall more effective than mineral oil regarding the reduction (HR 0.73). Eight comparisons demonstrated neutral results. Similarly, the occurrence of stroke was reduced in patients receiving EPA compared with patients receiving mineral oil (HR 0.74). Only 1 analysis found a reducing effect of EPA on stroke occurrence, whereas 8 other comparisons between EPA and placebo oils displayed neutral findings.

In reducing coronary revascularisation, EPA was more effective than EPA plus DHA (HR 0.67), corn oil (HR 0.63), mineral oil (HR 0.65), and olive oil (HR 0.66). Five analyses showed neutral results. Finally, no significant effect was found of EPA or EPA plus DHA on all-cause death versus placebo.

Although EPA outperformed a mineral oil placebo in the reduction of cardiovascular death, myocardial infarction, and stroke, the use of mineral oil as a placebo oil is questionable as mineral oil has been associated with increased apolipoprotein B, LDL cholesterol, and hs-CRP levels, and coronary artery plaque progression [2,4].

The observed effects of EPA on cardiovascular events are mostly neutral. Small beneficial effects of EPA have been observed for certain cardiovascular outcomes. However, the authors were unable to analyse participants with a low cardiovascular risk. Also, different regimens and doses of omega-3 fatty acids and placebo oils and heterogeneity in follow-up periods were reported. Therefore, a definite conclusion regarding the impact of EPA on cardiovascular outcomes cannot be made.

1. 
   
   1. Yokoyama Y, et al. Network Meta-Analysis of Randomized Controlled Trials of Eicosapentaenoic Acid for Cardiovascular Events Reduction. LF.RFO.13, AHA 2021 Scientific Sessions, 13­–15 November.
   2. Bhatt DL, et al. N Engl J Med 2019;380(1):11–22.
   3. Sharma G, et al. JAMA. 2020;324(22):2262–2264.
   4. Budoff MJ, et al. Eur Heart J. 2020;41(40)3925–2932.

 

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Posted on 14 January 202227 March 2024