ACC.23: Amarin Highlights New Evidence of Therapeutic Value of EPA in Reducing Cardiovascular Events in At-Risk Patients

--In Vitro Data Presentations Support Antithrombotic and Antioxidant Effects of EPA Compared with DHA, No Impact of Mineral Oil on Rates of LDL Oxidation -–  

Amarin Corporation plc highlighted new in vitro data supporting the potential mechanistic effects of eicosapentaenoic acid (EPA) in reducing cardiovascular events in at-risk patients presented at the joint ACC.23 together with the World Congress of Cardiology (ACC.23/WCC) in New Orleans, LA, March 4-6, 2023.   

“The findings shared at ACC.23/WCC provide additional insight into the unique role of EPA in reducing cardiovascular events in at-risk patients around the world. The potential novel antithrombotic mechanisms of EPA that may contribute to reduced ischemic events is particularly noteworthy given a new analysis from the REDUCE-IT trial showed that icosapent ethyl, a pharmaceutical formulation of EPA, significantly reduced the risk of first and total ischemic events in patients with recent acute coronary syndrome without significantly increasing bleeding,” said R. Preston Mason, PhD, MBA, Professor of Medicine at Harvard Medical School and Researcher    

“Additionally, from these in vitro analyses we see that EPA is highly effective in reducing lipoprotein oxidation, a central driver of atherosclerosis, and would therefore be considered protective against heart disease.  These mechanisms may help explain the significant risk reduction benefit demonstrated in the REDUCE-IT trial for icosapent ethyl. Our research also underscores confidence in the results of REDUCE-IT with mineral oil because that placebo comparator did not have any biologically active effects on LDL oxidation in our experiment.”    

The ACC.23/WCC 2023 presentations were as follows:  

• Eicosapentaenoic Acid (EPA) Modulated Expression of Proteins Linked to Platelet Activation and Thrombosis in Vascular Endothelial Cells during Inflammation  

  Highlights: This in vitro study suggests potential antithrombotic mechanisms for EPA that may contribute to reduced ischemic events.  EPA modulated expression of proteins involved in platelet activation and thrombosis under inflammatory conditions, including increased levels of tissue factor pathway inhibitor in vascular endothelial cells. Importantly, these findings follow data from REDUCE-IT ACS, also presented at ACC.23/WCC, showing bleeding rates were not more frequent with icosapent ethyl than placebo despite extensive use of background antithrombotic therapy.  

  • Pharmaceutical Grade Mineral Oil and Corn Oil do not Influence Phospholipid Membrane Oxidation Rates Compared to Omega-3 Fatty Acids In Vitro  

  Highlights: This in vitro study compared the effects of pharmaceutical grade mineral oil, corn oil, EPA, or DHA on rates of membrane lipid oxidation and found that EPA had potent antioxidant effect in membranes that were sustained over time compared with DHA and that placebo oils had no effects on oxidation even at very high levels.  The data showed EPA inhibited membrane oxidation by 89% compared to vehicle after 72 hours (p<0.001), while DHA mildly inhibited oxidation (21%) at this time point versus vehicle (p<0.05). There was no change in the oxidation rate in membranes incubated with either placebo through 72 hours.  

  • Comparing the Effects of Pharmaceutical Grade Mineral Oil, Corn Oil, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) in a Model of Atherosclerosis In Vitro  

  Highlights: This in vitro study found EPA had potent antioxidant effects in apolipoprotein B (ApoB) particles compared to DHA-containing formulations and that pharmaceutical grade mineral oil and corn oil did not influence LDL oxidation even at supra-pharmacologic levels. To compare the effects of these compounds on oxidation of LDL, LDL was isolated from human plasma, separated into test samples and incubated with pharmaceutical grade mineral oil, corn oil, EPA or DHA. All samples were then subjected to induced oxidation. At four hours, oxidation increased 15-fold and 57-fold in vehicle-treated small dense LDL (sLDL) and very-low-density lipoprotein (VLDL), respectively, and was unaffected by mineral oil or corn oil. By contrast, EPA significantly inhibited sdLDL and VLDL oxidation by 75% and 94%, respectively, compared with vehicle (p<0.001). While DHA exhibited antioxidant activity at 2 hours at a level less than EPA, this effect was eliminated by 4 hours.  

About Amarin  

Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our scientific research foundation to our focus on clinical trials, and now our commercial expansion, we are evolving and growing rapidly. Amarin has offices in Bridgewater, New Jersey in the United States, Dublin in Ireland, and Zug in Switzerland as well as commercial partners and suppliers around the world. We are committed to rethinking cardiovascular risk through the advancement of scientific understanding of the impact on society of significant residual risk that exists beyond traditional therapies, such as statins for cholesterol management.