European Medicines Agency versus Italian Medicines Agency indications for icosapent ethyl: a long and winding road

Background and aims: Residual cardiovascular risk remains high after acute coronary syndrome (ACS) despite intensive LDL-cholesterol lowering. Elevated triglycerides may contribute to this risk. Although icosapent ethyl (IPE) has shown cardiovascular benefit in high-risk statin-treated patients, access in Italy is limited by Italian Medicines Agency (AIFA) reimbursement criteria, which are more restrictive than the European Medicines Agency (EMA) indications. We compared EMA and AIFA eligibility for IPE in a real-world post-ACS cohort, assessed the association of triglyceride levels and variability with 12-month ischemic recurrence, and explored the potential economic impact of broader IPE use. Methods and results: This retrospective observational study included 430 consecutive adults admitted for ACS to a tertiary hospital in Italy in 2024, with 12-month follow-up. During follow-up, 48 patients (11.2%) experienced recurrent ACS. Diabetes mellitus was independently associated with recurrence (OR 2.90, 95% CI 1.41-5.97; p = 0.004), whereas male sex was protective (OR 0.46, 95% CI 0.23-0.93; p = 0.030). Absolute triglyceride levels were not significantly associated with recurrence, whereas triglyceride variability was: the coefficient of variation remained independently associated with recurrent events (OR 1.04, 95% CI 1.00-1.09; p = 0.029). According to EMA criteria, 35 patients (8.1%) were eligible at discharge and 15 (3.5%) at first follow-up; under AIFA criteria, only one patient was eligible. Conclusions: A marked discrepancy exists between EMA indications and AIFA reimbursement criteria for IPE, resulting in restricted access for high-risk post-ACS patients. Broader access, aligned with current evidence, may improve secondary prevention and represent a cost-effective strategy.