Challenges in achieving LDL-C goals: Insights from the Italian SANTORINI study cohort

Background and aims: Cardiovascular disease continues to be the leading cause of death worldwide, with atherosclerotic cardiovascular disease (ASCVD) being a major contributor. Elevated low-density lipoprotein cholesterol (LDL-C) levels are an important risk factor, which led to updated guidelines from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) in 2019 recommending lower LDL-C goals for patients at high- and very high-risk. However, many patients do not achieve the recommended LDL-C levels. The SANTORINI study was initiated to evaluate lipid management across Europe. This report presents the results of the 1-year follow-up of the Italian cohort. Methods and results: The study included 2095 patients, with 1993 having 1-year follow-up data. At baseline, 32 % of patients were not receiving lipid-lowering therapy (LLT), decreasing to 2.1 % at follow-up. Monotherapy use increased from 34.2 % to 41.0 %, while combination therapy use increased from 33.8 % to 55.5 %, particularly with high-intensity statin and ezetimibe combinations. LDL-C levels decreased from 2.5 to 1.9 mmol/L overall, with a greater reduction in very high-risk patients. The proportion of patients achieving LDL-C goals increased from 20.8 % to 35.0 %. Cardiovascular events were more frequent in very high-risk patients, with 11 cardiovascular deaths and 80 major adverse cardiovascular events (MACE). Conclusion: The Italian cohort of the SANTORINI study demonstrated improved LLT usage and LDL-C management, with a shift towards combination therapy. Despite these improvements, only one-third of patients achieved guideline-recommended LDL-C goals, highlighting the need to further optimise lipid-lowering strategies to reduce cardiovascular risk. Trial registration: ClinicalTrials.gov Identifier: NCT04271280.