Why the Differing Effects of Omega-3 Fatty Acids on ASCVD Risk in the REDUCE-IT vs. STRENGTH Trials?

Adverse effects on lipids and C-reactive protein due to the mineral oil placebo in REDUCE-IT explains some but not all of the difference.

The REDUCE-IT and STRENGTH trials reported differing results for the effect of high-dose omega-3 fatty acids on triglyceride lowering to prevent atherosclerotic cardiovascular disease (ASCVD). REDUCE-IT randomized participants to 4 g/day icosapent ethyl (an eicosapentaenoic acid [EPA]–only omega-3 fatty acid preparation) or mineral oil for 4.9 years and found a 25% lower risk of ASCVD (NEJM JW Cardiol Jan 2019 and N Engl J Med 2019; 380:11). In contrast, STRENGTH randomized participants to 4 g/day EPA (75%) plus docosahexaenoic acid (DHA; 25%) or corn oil for 3.5 years; it found no effect on ASCVD risk (NEJM JW Cardiol Jan 2021 and JAMA 2020; 324:2268).

Investigators studied whether differences in effects on lipid parameters and C-reactive p…

Reviewing Author

Karol E. Watson, MD, PhD, FACC

Disclosures

Consultant/Advisory BoardBoehringer Ingelheim; Amgen; Novartis; Lilly; Amarin

Speaker’s BureauBoehringer Ingelheim

Grant/Research SupportNIH

Editorial BoardsCirculation (Associate Editor)