Impact of icosapent ethyl on serum lipoand glycoprotein profiles assessed by 1H-NMR. A real-world observational study (IPE-NMR)

Background Icosapent-ethyl (IPE) has been shown to reduce cardiovascular events in a randomized trial; however, its real-world impact on advanced lipoprotein and inflammatory profiles remains incompletely characterized. We evaluated the effects of IPE on lipoprotein particle number, size, composition, and circulating glycoproteins using proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy in real-world clinical practice. Methods This multicentre, prospective, open-label observational study included patients with established atherosclerotic cardiovascular disease receiving IPE 2 g twice daily for ≥4 months in addition to optimized lipid-lowering therapy. Lipoprotein subclasses and Glyc acetyl signals were quantified by 1 H-NMR at baseline and follow-up. Changes were assessed using paired statistical tests, and analyses were stratified according to tertiles of triglyceride (TG) response. Results Sixty-two patients completed paired NMR assessments. Mean age was 64 years, 17.7% were women, median baseline LDL-cholesterol was 1.50 (1.09–1.82) mmol/L, and median TG concentration was 2.35 mmol/L (2.01–3.16). Overall TG levels decreased with substantial interindividual variability; tertiles 2 and 3 showed mean TG reductions of −21.6% and −38%, respectively, while tertile 1 were non-responders (less than 10% TG reduction). In responders, IPE therapy significantly reduced triglyceride-rich lipoprotein particles, particularly small VLDL remnants, as well as remnant cholesterol and small LDL particles. HDL triglyceride content was also reduced. The Glyc acetyl were also significantly reduced, indicating decreased systemic inflammation. Conclusions In a real-world secondary prevention population, IPE therapy significantly improved atherogenic lipoprotein profiles and inflammatory biomarkers, supporting its role in reducing residual cardiovascular risk beyond triglyceride lowering.