Study Finds Icosapent Ethyl Can Reduce Cardiovascular Risk, Even in Well-Controlled LDL-C

New data from an analysis of the landmark REDUCE-IT trial sheds further light on the benefit of icosapent ethyl (Vascepa) among patients with well-controlled LDL-C.

Results of the analysis demonstrated use of icosapent ethyl was associated with a reduced rate of cardiovascular end points irrespective of baseline LDL‐C, with data indicating those with LDL-C less than 55 mg/dL at baseline experienced a statistically significant 34% reduction in cardiovascular events.1

“As we know, LDL-C is a well-established major CV risk factor. These data are important and show that among adults with increased CV risk and elevated TGs, IPE clearly reduced the rate of CV outcomes irrespective of baseline LDL-C, including in those with very well-controlled LDL-C <55 mg/dL,” said Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and principal investigator for REDUCE-IT.2 “These data highlight the pressing need for immediate action – in high-risk patient populations, we must go beyond standard of care therapies and augment our foundational treatments with the best evidence-based and complementary interventions to urgently reduce the risk of cardiovascular events."

A multicenter, randomized, double-blind, placebo-controlled trial REDUCE-IT was used as the basis of icosapent ethyl’s 2019 US Food and Drug Administration approval for reducing as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with triglyceride levels of ≥150 mg/dL and established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for cardiovascular disease. Since its initial publication, the trial has been the subject of more than a dozen post-hoc analyses examining the effects of the agent across various subgroups and differing outcome measures, including an ACC.24 analysis concluding the benefit of icosapent ethyl on cardiovascular events was consistent irrespective of baseline LDL-C.1,2,3

In the current study, which was published in the Journal of the American Heart Association, investigators planned to assess the effects of icosapent ethyl use on primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina based on baseline LDL-C level. Among the 8179 people included in the REDUCE-IT trial, 8175 had baseline LDL-C available. Of these, 87.1% (n=7117) had an LDL of 55 mg/dL or greater at baseline and 12.9% (n=1058) had a baseline LDL-C of less than 55 mg/dL.1

Upon analysis, results indicated the rate of the primary endpoint events among patients with a baseline LDL-C less than 55 mg/dL was reduced among the icosapent ethyl group (16.2% vs 22.8%) relative to their counterparts in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50 to 0.87]; absolute risk reduction, 6.6%; P = .003). Among patients with LDL‐C of 55 mg/dL or greater at baseline, a primary outcome event was observed among 17.4% of the icosapent ethyl group and 21.9% among the placebo group (HR, 0.76 [95% CI, 0.69 to 0.85]; absolute risk reduction, 4.5%; P <.0001). Investigators pointed out there were no significant interactions observed between baseline LDL‐C and treatment group (P = .40).1

Investigators highlighted a secondary analysis examining a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. In patients with a baseline LDL-C less than 55 mg/dL, such an event occurred among 9.5% of the icosapent ethyl group and 15.9% among the placebo group (HR, 0.55 [95% CI, 0.39 to 0.78]; absolute risk reduction, 6.4%; P = .0007). In patients with a baseline LDL-C of 55 mg/dL or more, such an event occurred among 11.5% of the icosapent ethyl group and 14.7% of the placebo group (HR, 0.76 [95% CI, 0.67 to 0.87]; absolute risk reduction, 3.2%; P <.0001).1

“These findings tell us that our product, [icosapent ethyl], with its established efficacy and safety profile, is a clear complementary therapeutic option to add to existing current standard of care approaches for lowering the risk of cardiovascular disease – still the world’s leading killer," said Aaron Berg, president and CEO of Amarin.2 "Critically important is the fact that use of [icosapent ethyl] by clinicians can have a profound impact on outcomes for these patients across the cardiovascular risk reduction landscape.”

References:

1. Aggarwal R, Bhatt DL, Steg PG, et al. Cardiovascular Outcomes With Icosapent Ethyl by Baseline Low-Density Lipoprotein Cholesterol: A Secondary Analysis of the REDUCE-IT Randomized Trial. J Am Heart Assoc. Published online February 19, 2025. doi:10.1161/JAHA.124.038656
2. Amarin Corporation. Amarin Marks Key Milestone for VASCEPA®/VAZKEPA® (Icosapent Ethyl) -- Publication of Post Hoc Analysis of REDUCE-IT in Journal of the American Heart Association Reports Benefit on Top of Cholesterol Lowering. Amarin Corporation. February 27, 2025. Accessed February 28, 2025. https://www.amarincorp.com/news-and-media/amarin-marks-key-milestone-vasceparvazkepar-icosapent-ethyl.
3. Campbell P. Reduce-it analysis outlines benefit of icosapent ethyl across range of LDL-C Levels. HCP Live. April 18, 2024. Accessed February 28, 2025. https://www.hcplive.com/view/reduce-it-analysis-outlines-benefit-of-icosapent-ethyl-across-range-of-ldl-c-levels.