LDL-C goal achievement and lipid-lowering therapy in patients by atherosclerotic cardiovascular disease subtype: the SANTORINI study

Abstract

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

2022: The Year in Cardiovascular Disease – The Year of Upfront Lipid Lowering Combination Therapy.

“…Comparing this data with the results of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry for ACS patients, which includes data up to 2016, it appears that there has been no improvement, as 6 years ago we observed the HIS ratio of 37.4 and 39.1% in patients with STEMI and NSTEMI, respectively 12 . Even more dramatic examples of underuse of effective therapies are seen for patients treated with the combination therapy of statin and ezetimibe, and double/triple therapy with PCSK9 inhibitors [2][3][4][5][6]13,14 . In the TERCET registry the proportion of patients on the combination therapy with ezetimibe was only 0.3% of patients with myocardial infarction (MI), and 3.5% in those with stable coronary artery disease 12 .…”

“…In the SANTORINI study, as many as 21.4% of ASCVD patients received no statin 6 . It is worth emphasizing that the true prevalence of SI is only <7% when it is diagnosed using approved definitions 27 .…”

“…Only a very small percentage of patients at extremely high-risk, reach the goal of < 40 mg/dl (1 mmol/l) [ 2 – 5 ]. The SANTORINI study, which was performed in 2020–2021, showed a small improvement of 2.7% over the DaVinci study which was completed in 2019 [ 6 ]. However, still only 20.7% of atherosclerotic cardiovascular disease (ASCVD) patients achieved their LDL-C goal.…”

“…However, still only 20.7% of atherosclerotic cardiovascular disease (ASCVD) patients achieved their LDL-C goal. This study also clearly showed that these disappointing findings are associated with a very poor therapeutical approach in patients with cerebral ASCVD and peripheral artery disease (PAD) – with only 15 and 18.6% reaching LDL-C goals, respectively [ 6 ]. The latter group present a real unmet need in most of the departments of cardiology in Europe, as PAD is very rarely diagnosed – despite the recognition of a very strong link between PAD and ASCVD and cardiovascular events.…”

“…The main reason for such a large extent of underperformance is the lack of use of high intensity statin (HIS) therapy. Less than 25% patients received HIS therapy in the SANTORINI study [ 6 ]. The corresponding figure was 32% in CEE countries and 38% in the Europe based on the DaVinci study [ 2 , 3 ].…”