Icosapent ethyl modestly impacts various biomarkers linked with atherosclerotic disease: REDUCE-IT

Patients receiving mineral oil in the placebo arm of REDUCE-IT had worsening of various biomarkers linked to atherosclerotic disease during the trial, whereas those in the icosapent ethyl (Vascepa; Amarin) arm saw "minimal changes," according to new analysis.

There were increases in interleukin-1β (IL-1β), lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), lipoprotein(a), and homocysteine with use of mineral oil. In addition oxidized LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) also increased in line with previously released data.

The findings of this study were published in the American Heart Association Circulation.

The Reduction of Cardiovascular Events With Icosapent Ethyl—Intervention Trial (REDUCE-IT) found that using icosapent ethyl reduced the risk of significant adverse cardiovascular events by 25% when compared to pharmaceutical grade mineral oil. The mechanisms behind this advantage are still unknown. As a result, this study was done to determine if treatment allocation in REDUCE-IT affected a number of biomarkers in pathways known to be associated with atherosclerosis risk.

For this study, serum levels of interleukin-1, high-sensitivity C-reactive protein, interleukin-6, homocysteine, lipoprotein(a), oxidised low-density lipoprotein cholesterol, and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline, 12 months, 24 months, and at the end-of-study visit among REDUCE-IT participants with triglyceride levels >135

The key findings of this study were as follow:

1. The median values of each biomarker in the two therapy groups were comparable at baseline.

2. At 12 months, the median percent increase from baseline for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidised low-density lipoprotein cholesterol, 16.2% for interleukin-6, 18.5% for lipoprotein-associated phospholipase A2, and 21.9% for high-sensitivity C-reactive protein was 1.5% in this group.

3. These biomarkers changed very little in the icosapent ethyl group after 12 and 24 months.

4. As a result, at the end of the study, between-group treatment differences were largely reflected in the mineral oil group, with median percent differences of 2.4% for lipoprotein(a), 3.0% for homocysteine, 4.2% for oxidised low-density lipoprotein cholesterol, 19.8% for interleukin-6, 26.2% for Lp-PLA2, 38.5% for high-sensitivity C-reactive protein, and 48.7% for interleukin.

5. These findings are similar with earlier REDUCE-IT findings, in which the median percentage change in low-density lipoprotein cholesterol was 1.2% among those assigned to icosapent ethyl and 10.9% among those assigned to the mineral oil comparator at 12 months.

Reference:

Ridker, P. M., Rifai, N., MacFadyen, J., Glynn, R. J., Jiao, L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Tardif, J.-C., Ballantyne, C. M., Mason, R. P., & Bhatt, D. L. (2022). Effects of randomized treatment with icosapent ethyl and a mineral oil comparator on interleukin-1β, interleukin-6, C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2: A REDUCE-IT biomarker substudy. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.122.059410