Amarin REDUCE-IT legacy analysis suggests durable CV benefit after IPE
Amarin Corporation has presented a post hoc analysis from its REDUCE-IT cardiovascular outcomes trial at the European Society of Cardiology Congress 2026 in Munich, suggesting that the cardiovascular benefits of icosapent ethyl (IPE) may persist for years after patients stop taking the drug, provided they were sufficiently adherent during treatment.
The analysis, which the company describes as exploratory, drew on data from the 8,179 participants enrolled in REDUCE-IT, the landmark trial whose primary results were published in the New England Journal of Medicine in 2018. The intention-to-treat population showed a 25% relative risk reduction in a composite endpoint covering nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, coronary revascularisation, and unstable angina. Among the 6,921 participants classified as high adherers, defined as those who remained on study drug for at least 1.5 years, IPE was associated with approximately a 29–30% relative risk reduction, suggesting that adherence amplifies the treatment effect.
Legacy effect in secondary prevention patients
The more novel finding concerns what the investigators term a legacy effect. In the secondary prevention cohort, 1,318 participants who discontinued study drug after a mean of 2.3 years on therapy continued to show separated Kaplan-Meier event curves throughout follow-up, with a hazard ratio of 0.73 for cardiovascular events occurring after discontinuation. Crucially, that hazard ratio was identical to the figure seen during active treatment, with no apparent diminution over a subsequent one to four years off-drug (mean off-treatment period: 2.1 years).
Steven Ketchum, EVP and Chief Scientific Officer at Amarin, said the findings "suggest that patients who remained adherent on treatment long enough to achieve the full benefit of therapy may continue to experience cardiovascular protection for additional years after discontinuation."
Chris Packard, Professor of Vascular Biochemistry at the University of Glasgow, drew a comparison to the West of Scotland Coronary Prevention Study, in which five years of statin therapy was associated with cardiovascular benefits that persisted across two decades of follow-up. He said the REDUCE-IT legacy data suggest IPE may "influence the trajectory of CV disease, resulting in durable clinical benefits beyond the period of active treatment."
Market and regulatory context
The legacy effect concept is already familiar in cardiovascular medicine through statin and blood pressure trial data, but it is less established for lipid-modifying agents targeting triglycerides. For Amarin, demonstrating durability of effect is commercially significant. VASCEPA, the US brand of IPE, has been prescribed more than thirty million times since its expanded cardiovascular indication launched in January 2020, yet the company faces generic competition following patent litigation losses in earlier years.
In Europe, VAZKEPA received EU marketing authorisation in March 2021 and is now approved in more than a dozen markets. Generating post hoc evidence of durable benefit could support payer and prescriber retention arguments in markets where reimbursement negotiations are ongoing.
Investors and clinicians will note that this is a post hoc, exploratory analysis rather than a pre-specified endpoint, and the findings have not yet undergone peer review. The secondary prevention cohort that discontinued treatment was a self-selected group, which introduces potential confounding. Nevertheless, the hazard ratio consistency across the on-treatment and post-treatment periods is a data point that will attract attention as Amarin continues to defend VASCEPA's clinical differentiation in a competitive landscape that increasingly includes generic omega-3 preparations alongside approved alternatives.