Abstract Background The ESC/EAS 2019 guidelines recommend ambitious lower goals for low-density lipoprotein cholesterol (LDL-C), especially for patients with high and very high cardiovascular (CV) risk which could necessitate more intensive lipid-lowering therapy (LLT) regimens. Multiple real-world studies in Europe have demonstrated suboptimal achievement of older 2016 LDL-C goals, with combination therapy with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors (PCSK9i) used in 9% and 1% of patients, respectively. SANTORINI is the first European observational study since the 2019 guidelines to assess whether management of high- and very high-risk patients has improved. Purpose To describe patient characteristics and treatment patterns of LLT in real-world practice for the management of LDL-C levels in high- and very high-risk patients. Methods Baseline data were assessed from SANTORINI, which recruited patients aged ≥18 years with high and very high CV risk requiring LLT. Risk was defined as per a commonly available assessment system, e.g. the Systematic Coronary Risk Estimation (SCORE) system, for which ESC/EAS guidelines classify high-risk and very high-risk as a calculated 10-year risk of fatal CV disease of ≥5–<10% and ≥10%, respectively. Patients were recruited from 14 European countries across primary and secondary care settings, with patient characteristics, medical history, current LLT and other co-medications documented at baseline. Results Of 9606 patients recruited from March 2020 to February 2021 (55.0% from secondary care), cleaned data on 4308 were available through to February 2021. In this interim report, mean (standard deviation [SD]) age was 64.8 (10.8) years and 27.8% were female. Mean (SD) LDL-C was 2.45 (1.21) mmol/L. The majority of patients were classified as very high risk (69.3%), with 30.6% high risk. ESC/EAS guidelines were the most common basis for risk classification (51.3%), then clinical experience (33.5%) and national guidelines (10.4%). Concomitant CV risk factors included being a current or former smoker (16.5% and 41.8%, respectively), hypertension (70.9%), diabetes (35.4%) and familial hypercholesterolemia (10.1%). At baseline, 18.6% of patients were not receiving any LLT. 54.1% of patients were receiving LLT monotherapy, including 51.1% on statins, 1.4% ezetimibe, 1.2% a PCSK9i, and 0.5% other oral LLT. Combination therapy was used in 27.3% of patients, including 17.1% receiving statin plus ezetimibe, 4.1% PCSK9i plus oral LLT, and 6.1% any other oral combination therapy. Conclusions This large study in patients at high and very high CV risk from 14 European countries suggests that, although the ESC/EAS guidelines are the most frequently used basis for risk classification, LDL-C levels remain substantially higher than recommended goals, with combination therapies underutilised. An expanded data cut from SANTORINI will be reported in 2021. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany