National Lipid Association

National Lipid Association

Issue: February 2021
Source: Miller M, et al. Late-breaker presentations. Presented at: National Lipid Association Scientific Sessions; Dec. 10-12, 2020 (virtual meeting).
Disclosures: The REDUCE-IT trial was funded by Amarin. Miller reports he is a scientific adviser to Amarin and served on the steering committee for the REDUCE-IT study.
December 18, 2020
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CV benefits of icosapent ethyl may increase as daily EPA levels increase

Issue: February 2021
Source: Miller M, et al. Late-breaker presentations. Presented at: National Lipid Association Scientific Sessions; Dec. 10-12, 2020 (virtual meeting).
Disclosures: The REDUCE-IT trial was funded by Amarin. Miller reports he is a scientific adviser to Amarin and served on the steering committee for the REDUCE-IT study.
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Improvements in CV outcomes from hypertriglyceridemia treatment with icosapent ethyl, compared with placebo, increased as daily levels of eicosapentaenoic acid increased, according to an analysis of the REDUCE-IT trial.

Moreover, these benefits were consistent, regardless of eicosapentaenoic acid (EPA) levels at baseline.

puzzle pieces in shape of heart
Source: Adobe Stock.
Michael Miller

“Benefits were well beyond what can be explained by the degree of triglyceride lowering or other biomarker changes,” Michael Miller, MD, professor of cardiovascular medicine at the University of Maryland School of Medicine, said during a presentation at the virtual National Lipid Association Scientific Sessions. “On-treatment EPA levels via icosapent ethyl correlated strongly with the primary endpoint and the key secondary endpoint. These data provide a mechanistic underpinning for the large risk reductions seen in multiple endpoints with icosapent ethyl in the REDUCE-IT trial.”

As Healio previously reported, in the REDUCE-IT study presented at the American Heart Association Scientific Sessions in 2018, icosapent ethyl (Vascepa, Amarin) compared with placebo reduced risk for ischemic events in patients with elevated triglycerides and high CV risk despite statin therapy.

According to the presentation, icosapent ethyl 4 g daily reduced first CV events by 25% and total events by 31%.

For REDUCE-IT EPA, researchers evaluated the association between on-treatment EPA levels and CV outcomes among patients taking icosapent ethyl.

The primary composite endpoint included CV death, MI, stroke, coronary revascularization and unstable angina. The key secondary composite endpoint included CV death, MI and stroke.

Researchers found that icosapent ethyl reduced the risk for the primary endpoint (HR = 0.75; 95% CI, 0.68-0.83), regardless of baseline EPA levels (P for interaction = .91), compared with placebo.

Similar results were observed for the key secondary endpoint (HR = 0.76; 95% CI, 0.65-.83; P for interaction = .9).

According to the presentation, patients with high triglycerides experienced a 363.9% median change in their daily average EPA levels across their median 4.9-year follow-up, compared with the placebo group, which had a 0.2% median change (P < .0001).

Among patients in the intervention group, those with the highest EPA levels experienced the most reduced risk for the primary and secondary composite endpoints and the individual outcomes of CV death and total mortality (P for all < .001) compared with patients in the placebo group. The placebo group’s EPA level rarely deviated from the baseline average of 26.1 g/mL throughout the duration of the trial, Miller said.

Moreover, participants with the highest EPA levels also experienced the greatest risk reductions for any MI, any stroke, coronary revascularization and unstable angina (P for all < .001) compared with placebo.

In addition, the benefits of elevated EPA levels from treatment with icosapent ethyl remained strong for the primary and secondary composite endpoints, despite the presence of established CVD (P for each < .001).

“There were some limitations in the study and they included that approximately 14% of the patients did not have baseline EPA levels,” Miller said during the presentation. “Although the baseline characteristics and outcomes between those with or without data were quite similar, an on-treatment dose response analysis for bleeding, serious bleeding and atrial fibrillation/flutter are not yet available.

“Keep in mind that the results only apply to this specific formulation of EPA. EPA within blood can distribute differentially and possibly result in differences in tissue distribution,” Miller said during the presentation. “It’s also important to note that omega-3 fatty acid mixtures do not just contain EPA, and a high percentage contain [docosahexaenoic acid].”

References:

Editor’s Note: This article was modified on January 26, 2020 to reflect updates to the data.