Abstract Introduction and Objectives Icosapent ethyl (IPE) has been shown to reduce major cardiovascular events in patients with atherosclerotic cardiovascular disease or diabetes mellitus with elevated triglycerides (TG) despite optimal lipid-lowering therapy. However, real-world evidence remains limited. The aim of this study was to evaluate the impact of IPE in routine clinical practice. Methods This retrospective, multicenter observational study including 343 patients treated with IPE 4 g/day between September 2023 and October 2025. We included patients with established atherosclerotic cardiovascular disease and TG ≥150 mg/dL and LDL 40–100 mg/dL despite optimal therapy. Clinical data, cardiovascular risk factors, comorbidities, and lipid-lowering treatment were collected. Laboratory parameters before and after treatment (total cholesterol, LDL-c, non-HDL-c, TG, CRP, complete blood count) were analyzed, and cardiovascular events and adverse effects were recorded. Results A total of 343 patients were included (mean age 66.1 ± 9.8 years, 61.1% male). Hypertension was present in 74.0%, type 2 diabetes in 59.9%, and dyslipidemia in 84.0%. Ischemic heart disease was documented in 94.7%, and chronic kidney disease in 20.9%. Regarding baseline therapy, 92.9% were on statins, 85.7% on high-intensity statins, 69.5% on ezetimibe, 8.6% on PCSK9 inhibitors, and 11.6% on fibrates. The median time between baseline and follow-up blood tests was 4.1 months (IQR 2.2–5.9), with good adherence in 84.6% of patients. IPE therapy resulted in a significant reduction in the atherogenic lipid profile, lowering triglycerides by 26.1% (254.1 ± 110.0 mg/dL vs. 187.7 ± 110.2 mg/dL), total cholesterol by 14.5% (140.5 ± 43.0 mg/dL vs. 120.1 ± 32.8 mg/dL), non-HDL-c by 23.2% (105.7 ± 41.4 mg/dL vs. 81.1 ± 27.9 mg/dL) and LDL-c by 18.3% (60.1 ± 32.7 mg/dL vs. 49.1 ± 26.2 mg/dL) (all p0.001). In the subgroup with available C-reactive protein (n=37), a 67.2% reduction was observed (9.1 ± 14.5 mg/L vs. 3.0 ± 7.4 mg/L). No relevant changes were seen in hemoglobin, leukocytes, or lymphocytes. During follow-up of 63.6 patient-years, 10 patients experienced acute myocardial infarction (15.7 events/100 patient-years), 5 unstable angina (7.9/100 patient-years), 16 required coronary angiography or revascularization (25.2/100 patient-years), and 6 deaths were recorded (9.4/100 patient-years). No strokes were documented. Regarding safety, there were 2 cases of new-onset or decompensated atrial fibrillation/flutter (0.6%), 6 clinically relevant non-major bleeding events (1.7%), none requiring drug discontinuation, and 2 cases of dysgeusia (0.6%). Conclusions In this real-world cohort of patients at very high cardiovascular risk, IPE was associated with significant improvement in the atherogenic lipid profile and reduction in inflammatory markers, with high adherence and a favorable safety profile. These findings support its use as a foundational therapy for residual risk management.
Vaca et al. (Mon,) studied this question.