Background In the 2019 ESC/EAS guidelines, documented ASCVD is a criterion for patients being categorised as at very high cardiovascular (CV) risk, and stringent low-density lipoprotein cholesterol (LDL-C) reductions of ≥50% plus a goal of <1.4 mmol/L are recommended. Intensive lipid lowering therapy (LLT) is therefore key to reducing the risk of future CV events. Purpose To describe patient characteristics, approaches to lipid management and LDL-C goal attainment at baseline in the subgroup of secondary prevention patients with a history of ASCVD enrolled in the SANTORINI study. Methods SANTORINI is a multinational observational study (NCT-04271280) evaluating the real-world use of LLT in adult patients with high- and very-high CV risk enrolled from primary and secondary care sites across Europe between March 2020 and February 2021. The ASCVD status of patients was defined based on medical records as either coronary (myocardial infarction; unstable angina; angina pectoris; coronary artery bypass graft surgery; percutaneous transluminal coronary angioplasty; coronary artery disease [CAD]; CAD unequivocal on imaging), cerebral (stroke; transient ischaemic attack; cerebrovascular disease; cerebrovascular disease unequivocal on imaging; carotid artery disease), peripheral/other (peripheral arterial disease [PAD]; lower extremity artery disease; PAD unequivocal on imaging; retinal vascular disease; abdominal aortic aneurysm; renovascular disease) or polyvascular (≥1 ASCVD). Results Of the 9044 patients included in the analysis 6954 (76.9%) had a history of ASCVD. Baseline demographics and patient characteristics by type of ASCVD are shown in Table 1. The majority of patients were male (76.9%) and mean (SD) age was 66.1 (10.4) years. Mean (SD) LDL-C level was 2.29 (1.13) mmol/L and a total of 20.7% of patients achieved CV risk-based LDL-C goals. Fewer patients with cerebral ASCVD attained LDL-C goals (15.0%). Despite being at very-high CV risk, 21.4% of all patients had no documented LLT (up to 28.5% for the cerebral ASCVD group). The majority of patients (49.2%) received statin monotherapy, particularly moderate (21.8%) and high-intensity statins (24.9%). The peripheral/other ASCVD and cerebral ASCVD groups recorded the highest use of monotherapy across subgroups (≥57.8%), whereas any other LLT alone was consistently low, including ezetimibe (≤2.5%) and PCSK9i (≤2.0%). Overall, only 25.6% of patients received combination therapy (17.5% statin + ezetimibe; 4.7% PCSK9i + statin and/or ezetimibe; 3.4% other). Conclusion The SANTORINI baseline analysis shows that the majority of patients with ASCVD do not achieve their LDL-C goals. The underutilisation of combination therapy in this very high CV risk population highlights the need to move beyond high-intensity statin monotherapy and rather focus on combination therapies which achieve more intensive LDL-C reductions, thus improving LDL-C goal attainment. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany

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Background Strategies for the prevention of atherosclerotic cardiovascular disease (ASCVD) are related to individual risk factors, and according to guidelines the higher the risk, the more intense the treatment required. Identifying patients at highest risk who might benefit the most from interventions is central for tailored solutions and ASCVD prevention, and any underestimation of risk may increase the ASCVD burden in these patients. Purpose To describe demographics and cardiovascular (CV) risk factors of patients with and without prior ASCVD enrolled in the SANTORINI study, as well as their CV risk as assigned by the investigator at the time of enrolment. Methods SANTORINI is an observational study (NCT04271280) conducted in 14 European countries and including patients aged ≥18 years with high- and very-high CV risk, as assessed by the investigator, and requiring lipid-lowering therapy. Patients were recruited between March 2020 and February 2021. The ASCVD status (coronary; cerebral; peripheral/other; polyvascular) of patients was defined based on medical records and the basis for risk classification was documented. For those whose risk was classified by the investigator based on the 2019 ESC/EAS guidelines, the CV risk was re-assessed centrally based on the information present in the study database to assess concordance. Results A total of 9044 patients were included in the analysis; of these, 76.9% had documented history of ASCVD (Table 1). Overall, the majority of patients were male (72.6%) and had a mean (SD) age of 65.3 (10.9) years. Mean (SD) LDL-C was 2.3 (1.13) mmol/L and 2.8 (1.37) mmol/L in the with and without ASCVD groups, respectively. Hypertension was common in both groups, whereas diabetes and familial hypercholesterolaemia were more prevalent in those without than those with ASCVD (44.6% vs 30.3% and 18.6% vs 7.2%, respectively). Patients with and without ASCVD had multiple CV risk factors (Table 1). Overall, ESC/EAS guidelines were cited as the most commonly used basis for risk classification (52.0%). Among all patients, the investigator assessed 26.0% and 84.2% of patients without and with ASCVD, respectively, as being very high-risk. However, central re-estimation for those using ESC/EAS guidelines suggested that 54.7% and 100% of those without and with ASCVD were at very high CV risk (Table 2). Conclusion Analysis of the SANTORINI baseline data shows that CV risk factors are common even in patients without documented ASCVD, and that the CV risk of patients both with and without ASCVD is underestimated in clinical practice, potentially contributing to clinical inertia in risk factor control. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany