Article Impact Level: HIGH Data Quality: STRONG Summary of Circulation, 0(0), 10.1161/CIRCULATIONAHA.122.059410. https://doi.org/10.1161/CIRCULATIONAHA.122.059410 Dr. Paul Ridker et al
Points
- The study aimed to determine whether REDUCE-IT treatment using icosapent ethyl had any effect on certain biomarkers associated with atherosclerosis
- The use of mineral oil returned an increase in atherosclerosis-related biomarker levels compared to those who were treated with icosapent ethyl; these results were also found to be consistent with previous REDUCE-IT results
Summary
The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) earlier reported a 25% decrease in relative risk for major adverse cardiovascular events when using ethyl eicosapentaenoic acid (icosapent ethyl) compared with the use of pharmaceutical-grade mineral oil. Despite these observations, any mechanisms that may lie beneath these results remain obscured from view. With this in mind, researchers set out to determine whether treatment under REDUCE-IT has any effect on certain biomarkers in pathways known to be associated with a risk of atherosclerosis.
To do the study, serum levels of interleukin-1β, interleukin-6, high-sensitivity C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline. These were measured at 12 months, at 24 months, and at the end-of-study visit among REDUCE-IT participants, all with triglyceride levels >135 mg/dL and <500 mg/dL. These participants, on the other hand, were randomly treated with four (4) grams daily of either icosapent ethyl or mineral oil used as a comparator.
The median levels of each biomarker were similar in the 2 treatment groups upon comparison at baseline. Atherosclerosis-associated biomarker levels increased over time among those treated with mineral oil; at 12 months, their median percent increases from baseline were as follows: 1.5% homocysteine, 2.2% lipoprotein(a), 10.9% oxidized low-density lipoprotein cholesterol, 16.2% interleukin-6, 18.5% lipoprotein-associated phospholipase A2, 21.9% high-sensitivity C-reactive protein, and 28.9% interleukin-1β (all P values <0.001). Similar changes were also observed at 24 months. Meanwhile, minimal changes were observed in these biomarkers within the icosapent ethyl group at both 12 and 24 months.
In conclusion, the differences between the two groups treated with different factors were seen as increases within the mineral oil group. These were seen as median percent differences of 2.4% for lipoprotein(a), 3.0% for homocysteine, 4.2% for oxidized 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-1β (all P values <0.007), all compared to those recorded for the icosapent ethyl group. These values were found to be consistent with previous REDUCE-IT results, where the median percent change for low-density lipoprotein cholesterol at 12 months was -1.2% among those allocated to icosapent ethyl compared to 10.9% among those allocated to mineral oil treatment.
Overall, icosapent ethyl treatment had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels increased among those allocated to mineral oil. Despite this, the effect these findings have on overall risk reduction interpretations in clinical events observed within REDUCE-IT remain uncertain.
Link to the article: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.059410
References Ridker, P. M., Rifai, N., MacFadyen, J., Glynn, R. J., Jiao, L., Steg, Ph. G., Miller, M., Brinton, E. A., Jacobson, T. A., Tardif, J.-C., Ballantyne, C. M., Mason, R. P., & Bhatt, D. L. (n.d.). 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, 0(0), 10.1161/CIRCULATIONAHA.122.059410. https://doi.org/10.1161/CIRCULATIONAHA.122.059410
