Do omega-3 supplements help lower CV risk?

Vascepa or Icosalip 2 g BID is approved to reduce CV risk in some high-risk patients with moderately elevated triglycerides despite statins....
Mahitab Hany, BS Pharm, PGDipClinPharm, PGDipClinNutrition

Do omega-3 fatty acid supplements reduce cv risk? Mounting evidence suggests they don't, despite prior evidence with Vascepa OR Icosalip (icosapent ethyl), a form of EPA (eicosapentaenoic acid). Vascepa or Icosalip 2 g BID is approved to reduce CV risk in some high-risk patients with moderately elevated triglycerides despite statins. Now evidence suggests that adding Epanova 4 g/day for about 3 years does NOT improve CV outcomes in high-risk patients on statins.

Epanova is a combo of EPA and DHA (docosahexaenoic acid) that was approved in 2014 for severely high triglycerides over 500 mg/dL. But the company held its launch, while awaiting results of this CV trial. Other new data show no CV benefit of a European omega-3 product with 1.8 g/day EPA and DHA after about 2 years in seniors with a recent MI. Plus older studies with omega-3 doses of about 1 g/day are conflicting or suggest only slight benefit in some CV patients.

The contrasting data have researchers scratching their heads. Some question if DHA negates the CV benefit of EPA. Or if Vascepa's results were inflated by the study's mineral oil placebo, which may have increased CV risk, possibly by reducing statin absorption. For example, mineral oil raised LDL and high-sensitivity C-reactive protein. This wasn't seen with the Epanova study's corn oil placebo. Consider the CV benefits of omega-3s as questionable at best and that all omega-3s may NOT have the same effects. Other Omega-3s or fish oil supplements have both EPA and DHA. Be aware of risks. Omega-3s are linked with increased risk of atrial fibrillation and omega-3 doses above 3 g/day may increase bleeding.

NPS-adv

Don't rely on omega-3s for CV benefits. If needed, reinforce other measures an optimized statin, BP control, smoking cessation, etc. If a patient wants to use a fish oil supplement, encourage them to get one that's USP Verified. But point out that CV benefit isn't likely, no matter the dose or source (krill oil, etc).

References

  1. Nicholls SJ, Lincoff AM, Garcia M, Bash D, et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2268-2280.
  2. Kalstad AA, Myhre PL, Laake K, Tveit SH, et al. Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction: A Randomized, Controlled Trial. Circulation. 2021 Feb 9;143(6):528-539.
  3. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22.