Eligibility for Icosapent ethyl in patients undergoing cardiac rehabilitation: A real-world cohort study

Despite optimal lipid-lowering therapy, many patients with established cardiovascular disease (CVD) maintain elevated triglyceride (TG) levels, contributing to residual risk. Icosapent ethyl (IPE) has shown clinical benefit in patients with moderate hypertriglyceridemia. This study aimed to evaluate eligibility for IPE treatment based on REDUCE-IT and Italian Drugs Administration (AIFA) eligibility criteria.

We retrospectively analyzed 1129 patients referred to a cardiac rehabilitation program for a recent acute coronary syndromes or with a chronic coronary syndromes between 2012 and 2025. Fasting TG and LDL were assessed at admission and discharge. We identified patients eligible for IPE treatment based on REDUCE-IT (TG 135-499 mg/dL, LDL 40-100 mg/dL, statin therapy) and AIFA eligibility criteria (TG ≥200 mg/dL, LDL <70 mg/dL, BMI ≥27 kg/m², statin + ezetimibe therapies, age 18-80).

Median TG values significantly decreased from 117 (IQR 86-159) mg/dL at admission to 99 (79-132) mg/dL at discharge (p < 0.001). LDL also decreased from 106.7 ± 40.1 to 62.8 ± 24.8 mg/dL (p < 0.001). Based on REDUCE-IT criteria, 117 patients (10.4 %) were eligible for IPE while only 6 patients (0.53 %) met all AIFA eligibility criteria.

In a large real-world cohort of acute and chronic coronary syndrome undergoing cardiac rehabilitation, over 10 % of patients were theoretically eligible for IPE based on clinical trial criteria. However, less than 1 % met current AIFA eligibility conditions due to added restrictions, highlighting a significant barrier to implementation in clinical practice.