REDUCE-IT Analysis Outlines Benefit of Icosapent Ethyl Across Range of LDL-C Levels

Use of icosapent ethyl (Vascepa) was associated with regardless of baseline LDL-C levels, according to a new analysis of the REDUCE-IT trial.

Presented at the American College of Cardiology 2024 (ACC.24) Annual Scientific Session, results of the analysis underline the benefit of icosapent ethyl across the spectrum of LDL-C levels within the trial, including those in lower ranges.

“Among adults with increased CV risk and elevated [triglycerides], icosapent ethyl reduced the rate of [cardiovascular] outcomes irrespective of baseline LDL-C,” wrote investigators.

The pivotal trial supporting icosapent ethyl’s expanded approval for reducing cardiovaacular risk in 2019, REDUCE-IT was a multicenter, randomized, double-blind, placebo-controlled trial of 8179 patients randomized to 2 grams of icosapent ethyltwice daily or matching placebo with a primary composite endpoint of ardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. Results of the trial demonstrated use of icosapent ethyl was associated with a 25% reduction in risk of a primary outcome event relative to placebo therapy (Hazard Ratio [HR], 0.75; 95% Confidence Interval [CI], 0.68 to 0.83; P <.001).^2,3

Since it was initially published, the trial has been the subject of dozens of subsequent analyses assessing the benefits and safety profile across a multitude of patient subgroups, including an additional study from ACC.24 examining effects on risk among patients according to baseline lipoprotein(a) levels. In that analysis, icosapent ethyl provided cardiovascular event reductions across the range of lipoprotein(a) levels (P for interaction >.10), with reductions in risk observed for those with concentrations less than 50 mg/dL (HR, 0.75; 95% CI, 0.66 to 0.84) and those with concentrations greater than or equal to 50 mg/dL (HR, 0.79; 95% CI, 0.64-0.97).⁴

Presented by Rahul Aggarwal, MD, a cardiology fellow at Brigham and Women's Hospital, Harvard Medical School, the current analysis stratified patients in the trial based on whether or not their baseline LDL-C levels were less than 55 mg/dL. Of the 8179 patients included in the REDUCE-IT trial, 1058 (n=12.9%) had an LDL-C less than 55 mg/dL. The primary outcome of interest for the analysis was a composite of death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina, with differences assessed using Cox proportional hazards models.¹

Analysis of those with an LDL-C less than 55 mg/dL at baseline suggested a primary outcome event occurred among 16.2% of those receiving icosapent ethyl and 22.8% of the placebo group (HR, 0.66; 95% CI, 0.50 to 0.87; P = .003), with a number needed to treat of 15. Among those with an LDL-C of 55 mg/dL or greater, a primary outcome event was observed among 17.4% of those receiving icosapent ethyl and 21.9% of those receiving placebo therapy (HR, 0.76; 95% CI, 0.69 to 0.85; P < .0001), with a number needed to treat of 22. Further analysis indicated there was no signification interaction based on baseline LDL-C (P = .40).¹

“As we know, LDL-C is a well-established major [cardiovascular] risk factor. These data are important and show that among adults with increased [cardiovascular] risk and elevated [triglycerides], icosapent ethyl clearly reduced the rate of [cardiovascular] outcomes irrespective of baseline LDL-C, including in those with very well controlled LDL-C <55 mg/dL,” said principal investigator the REUDCE-IT trial Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital.⁵

References:

1. Aggarwal R, Bhatt DL, Steg PG, et al. EFFICACY OF ICOSAPENT ETHYL FOR REDUCING CARDIOVASCULAR OUTCOMES BY BASELINE LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Office of the Commissioner. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups. U.S. Food and Drug Administration. December 13, 2019. Accessed April 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups.
3. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792
4. Campbell P. Reduce-it lp(a) analysis details icosapent ethyl effect on Mace across LP(a) range. HCP Live. March 27, 2024. Accessed April 18, 2024. https://www.hcplive.com/view/reduce-it-lp-a-analysis-details-icosapent-ethyl-effect-on-mace-across-lp-a-range.
5. New reduce-IT® analyses show VASCEPA®/VAZKEPA® (icosapent ethyl) benefit in high-risk cardiovascular disease patient subgroups: Amarin Global. New REDUCE-IT® Analyses Show VASCEPA®/VAZKEPA® (Icosapent Ethyl) Benefit in High-Risk Cardiovascular Disease Patient Subgroups | Amarin Global. April 6, 2024. Accessed April 18, 2024. https://amarincorp.com/news-and-media/new-reduce-itr-analyses-show-vasceparvazkepar-icosapent-ethyl.