Physicians' Academy for Cardiovascular Education

Higher on-treatment EPA levels associated with reduced risk of CV outcomes

News - Apr. 2, 2020

EPA Levels and Cardiovascular Outcomes in the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Presented at ACC.20 by Deepak Bhatt (Boston, MA, USA)

Introduction and methods

The overall REDUCE-IT trial showed that use of 4 g icosapent ethyl was associated with a reduction in the primary endpoint, a composite of CV death, MI, stroke, coronary revascularization and unstable angina compared to placebo (HR 0.75, 95%CI:0.68-0.83, P<0.00000001). The key secondary endpoint of ‘hard endpoints’ CV death, MI and stroke was also reduced in the icosapent ethyl group compared to placebo (HR 0.74, 95%CI: 0.65-0.83). These results resulted in the question of what is driving this large risk reduction.

Main results


This sub-analysis of the REDUCE-IT showed that higher on-treatment EPA levels were associated with lower risk of CV outcomes, including the primary endpoint, the key secondary endpoint, MI, stroke, revascularization, unstable angina, sudden cardiac death, cardiac arrest, new heart failure, and all-cause death.

Bhatt pointed out that the observed effects in the REDUCE-IT trial appear to be mediated by EPA levels. Basic science studies have suggested that these effects are specific and can not be generalized to other EPA formulations beyond icosapent ethyl or to DHA.


This study validates the unique benefit of EPA, according to the discussant Eugene Yang, MD (Bellevue, WA, USA). Also in light of the STRENGTH CV trial that was terminated and evaluated a combination of EPA and DHA. There are different effects of EPA and DHA, as pointed out by prof. Bhatt and in combination may have unfavorable effects. A lower dose of EPA and DHA in the ASCEND trial published in 2018 also failed to show a CV benefit. It appears that EPA does not mediate its effects by lipid-lowering, but pleiotropic effects -anti-inflammatory effects or other targets that have yet to be elucidated- may be at play. Finally, he noted that better understanding of the increased risk of bleeding (although not significantly increased) observed with icosapent ethyl is necessary.

- Our coverage of ACC.20 is based on the information provided during the congress –

Watch a video by prof. Bhatt

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