Core Insights - The 2025 ESC/EAS Dyslipidemia Guideline Update reaffirms high-dose icosapent ethyl (IPE) as a Class IIA recommended therapy for high-risk or very high-risk patients to reduce cardiovascular events based on the REDUCE-IT trial findings [1][14] Group 1: REDUCE-IT Trial Findings - Three sub-analyses from the REDUCE-IT trial demonstrate significant reductions in cardiovascular disease (CVD) risk and outcomes associated with IPE administration in patients with cardiovascular-kidney-metabolic (CKM) syndrome, stratified by baseline apolipoprotein B (ApoB) and fasting triglyceride-rich lipoprotein cholesterol (TRL-C) levels [1][2] - IPE treatment showed a 44% relative risk reduction (RRR) for the primary composite endpoint in patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², with a hazard ratio (HR) of 0.56 (95% CI 0.39, 0.79), P = 0.001, and an absolute risk reduction (ARR) of 11.2% [4][5] Group 2: Impact on Major Adverse Cardiovascular Events (MACE) - IPE treatment resulted in significant reductions in MACE across all quartiles of baseline ApoB and TRL-C concentrations, with HRs ranging from 0.72 to 0.80 for ApoB and from 0.74 to 0.68 for TRL-C, all with P ≤ 0.02 [8][9] Group 3: Hospitalization and Mortality Outcomes - IPE significantly reduced total hospitalizations (HR 0.91, 95% CI 0.84, 0.98, P=0.017) and increased the likelihood of surviving without hospitalization (odds ratio (OR) 1.12, 95% CI 1.02, 1.22, P=0.016) [12][13] Group 4: Clinical Recommendations - The ESC/EAS guidelines recommend high-dose IPE for patients with elevated triglyceride levels (135–499 mg/dL) despite statin therapy, emphasizing its role in reducing CVD events [14]