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Higher serum levels of eicosapentaenoic acid correlate with reduced CV events

Presented by
Dr D. Bhatt, Brigham and Women's Hospital, USA
ACC 2020
REDUCE-IT EPA analysis
Compared with placebo, icosapent ethyl (IPE) 4 g/day has shown to significantly reduce first and total cardiovascular (CV) events, which is beyond what can be explained by the degree of triglyceride or other biomarker changes. It seems that serum levels of eicosapentaenoic acid (EPA) play an important role here [1].

Dr Deepak Bhatt (Brigham and Women's Hospital, USA) presented the results of the REDUCE-IT EPA analysis, which was based on the initial study including 8,179 patients at 473 sites in 11 countries who had elevated CV risk and were using statins. They were randomised to IPE 2 g twice daily (n=4,089) or placebo (n=4,090) with a mean duration of 4.9 years of follow-up. Results showed that icosapent ethyl 4 grams daily compared with placebo resulted in a reduced combined rate of first and subsequent non-fatal myocardial infarction, stroke, CV death, coronary revascularisation, or hospitalisations for unstable angina by 25% and 30%, respectively. Subsequently, serum EPA levels were measured and compared with the placebo group. Patients were grouped by EPA level tertiles (<20, 20-34, >34 ¬Ķg/mL) and averaged across visits.

Results suggest that higher EPA serum levels within the IPE group were strongly associated with reduced CV events; significant associations were found with all measured CV outcomes. The higher the serum EPA level was, the lower the rate of the various CV events, CV deaths, and even total mortality (P for interaction=0.91). Overall, the drug significantly increased serum EPA levels by 386% from baseline to 1-year when compared with placebo, and was sustained out to 5 years in the IPE arm (P<0.0001), while it remained more or less unchanged in the placebo arm. Docosahexaenoic acid (DHA) was also measured and its level decreased (-2.9%), suggesting that it plays no role in the observed CV benefits, which are considered to be the result of EPA. Also, patients with highest on-treatment EPA levels had a significant reduction in hospitalisations for new onset heart failure with the drug compared with placebo. Furthermore, significant associations were observed between on-treatment EPA levels and a lower risk of sudden cardiac death and cardiac arrest.

The results of this trial indicate that the use of IPE 2 g twice daily was superior to placebo in reducing triglycerides, CV events, and CV death among patients with high triglycerides and either known CV disease or those at high risk for developing it, and who were already on statin therapy with relatively well-controlled LDL levels. Dr Bhatt concluded that these are exciting findings that may open a new field of study and hopefully treatment options.

      1. Bhatt DL, et al. Abstract 411-14. ACC/WCC 28-30 March 2020.

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