The reduction in cardiovascular risk was greatest for eicosapentaenoic acid (EPA) alone rather than the combination of EPA and another omega-3 fatty acid.
For decades there has been a lot of interest in whether omega-3 fatty acids can lower the rate of cardiovascular events. In 2018, the results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were published in the New England Journal of Medicine and showed that a high dose of a purified ethyl ester of eicosapentaenoic acid (EPA) in patients with an increased cardiac output Risk significantly reduced cardiovascular events. The results of the study led to the approval of the prescription drug ikosapentethyl by the US Food and Drug Administration, Health Canada and the European Medicines Agency to reduce cardiovascular risk in patients with elevated triglycerides and to update global guidelines. But previous and subsequent studies of omega-3 fatty acid supplements that combine EPA and docosahexaenoic acid (DHA) had mixed results.
Researchers at Brigham and Women’s Hospital and elsewhere conducted a systematic review and meta-analysis of 38 randomized controlled trials of omega-3 fatty acids. Overall, they found that omega-3 fatty acids improved cardiovascular outcomes. The results, now published in eClinical Medicine, showed a significantly greater reduction in cardiovascular risk in studies with EPA alone compared to EPA + DHA supplements.
“REDUCE-IT ushered in a new era in cardiovascular prevention,” said senior author Deepak L. Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs at Brigham and lead investigator of the REDUCE-IT study. “REDUCE-IT was the largest and most rigorous EPA study to date, but there were others. Now we can see that all of the evidence supports robust and consistent benefits from EPA. “
Bhatt and colleagues performed a meta-analysis of 38 randomized clinical trials on omega-3 fatty acids, including trials on EPA monotherapy and EPA + DHA therapy. In total, these studies included more than 149,000 participants. They assessed key cardiovascular endpoints, including cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation. Overall, omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes. The studies with EPA showed a greater relative reduction in cardiovascular outcomes compared to those with EPA + DHA.
The researchers note that there are crucial biological differences between EPA and DHA – although both are considered omega-3 fatty acids, they have different chemical properties that affect their stability and potency, which they can have on cholesterol molecules and cell membranes. To date, no studies have examined the effects of DHA alone on cardiovascular outcomes.
“This meta-analysis sheds light on the role of omega-3 fatty acids, especially prescription EPAs,” said Bhatt. “It should encourage researchers to further study the cardiovascular effects of EPA in different clinical settings.”
Reference: “Effect of Omega-3 Fatty Acids on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis” by Safi U. Khan, Ahmad N. Lone, Muhammad Shahzeb Khan, Salim S. Virani, Roger S. Blumenthal, Khurram Nasir, Michael Miller, Erin D. Michos, Christie M. Ballantyne, William E. Boden, and Deepak L. Bhatt, July 8, 2021, eClinical Medicine.
DOI: 10.1016 / j.eclinm.2021.100997
REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Bhatt has done as a study director and as an international study director. The present analysis was not funded.