Eicosapentaenoic acid ethyl ester as an antithrombotic agent: comparison to an extract of fish oil

Evidence suggesting that dietary omega-3 polyunsaturated fatty acids decrease the risk of thrombosis comes mainly from studies involving supplementation with large amounts (15-20 g/day) of fish oil extract. We investigated the inhibition of platelet function by a moderate amount (4 g/d) of ethyl eicosapentaenoate (E-EPA) compared to a concentrated fish oil extract (6 g/d) when given as a supplement to an ordinary diet. We also determined the effects of these supplements on platelet EPA incorporation, thromboxane synthesis, calcium mobilization and fibrinogen binding. After 4 weeks, both omega-3 supplements increased the amount of EPA in platelet phospholipids. The fish oil extract, which contained docosahexaenoic acid (DHA), had increased the amount of DHA also. The total increase in omega-3 fatty acids was similar for both supplements. E-EPA decreased serum cholesterol by 13% and triacylglycerols, 35%; increased the bleeding time by 57% and the threshold dose of collagen needed to induce platelet aggregation by 46%. Thromboxane synthesis in response to collagen was decreased 65% by E-EPA. Thus, the dietary supplement of pure E-EPA was more effective in limiting platelet reactivity than a concentrated fish oil extract providing an equivalent amount of omega-3 fatty acids. As an antithrombotic agent, E-EPA should allow for reasonable daily doses in long-term treatment of cardiovascular disease.