Omega-3 fatty acids for the prevention of atherosclerotic cardiovascular disease

Pharmacotherapy. 2021 Dec;41(12):1056-1065. doi: 10.1002/phar.2615. Epub 2021 Aug 30.


Marine-derived omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are a type of polyunsaturated fatty acids with many purported beneficial health effects including the prevention of atherosclerotic cardiovascular disease (ASCVD) events. Omega-3 fatty acid intake may be supplemented via dietary sources, as well as prescription or non-prescription products. Omega-3 fatty acids have been shown to reduce serum triglycerides, but there remains ongoing debate regarding the effect of omega-3 fatty acids on major adverse cardiovascular events in patients with established, or at risk of, ASCVD. Recent evidence from randomized, placebo-controlled trials has demonstrated that low-dose (1 g daily or less) omega-3 fatty acids (DHA and EPA) do not reduce cardiovascular events or death in patients with or without established ASCVD. Contrarily, the REDUCE-IT trial demonstrated that a purified form of EPA ethyl esters (icosapent ethyl) at 4 g daily reduced cardiovascular events and death in patients with ASCVD (or diabetes and multiple cardiovascular risk factors) and elevated triglycerides on background statin therapy. However, 4 g daily of omega-3 carboxylic acids (DHA and EPA) did not show a cardiovascular benefit in the STRENGTH trial, which enrolled a similar population. The explanation for this observed discrepancy remains a source of contention and discourse. For now, icosapent ethyl has the most compelling evidence to support a cardiovascular benefit and should be considered in select patients who meet the REDUCE-IT criteria. Furthermore, alternative versions of omega-3 fatty acids should not be considered equivalent to icosapent ethyl. Patients taking an omega-3 fatty acid supplement should be monitored for potential adverse effects, including gastrointestinal disorders or bleeding, in addition to a possible increased risk of atrial fibrillation.

Keywords: cardiovascular diseases; dyslipidemia; fatty acids; omega-3.

Publication types

  • Review

MeSH terms

  • Atherosclerosis* / prevention & control
  • Cardiovascular Diseases* / prevention & control
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Randomized Controlled Trials as Topic


  • Fatty Acids, Omega-3