Very-high Cardiovascular Risk Research Articles

#1237 Management of dyslipidaemia with evolocumab in kidney transplant recipients

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have shown to reduce major adverse cardiovascular events in very-high cardiovascular risk patients, even with chronic kidney disease. However, the experience is very scarce in kidney transplant (KT) recipients. Method We performed a prospective cohort study of KT recipients who started evolocumab in our hospital (15/09/22–11/05/23) and were followed during at least 6 months. The criteria for its prescription were not achieving therapeutic c-LDL goals despite high-potency statins and ezetimibe treatment or adverse effects of statins (myalgias, hypertransaminasemia). Total cholesterol, c-LDL, triglycerides, estimated glomerular filtration rate (eGFR) and albuminuria were compared at baseline, 1st, 3rd and 6th month after starting the treatment. We also collected drug-related adverse effects and immunosuppressive trough levels. Results In this period, 13 KT started evolocumab. Previous lipid-lowering treatments were maintained. Mean KT vintage was 32.4 months and 69.2% had personal history of ischemic heart disease. Median follow-up was 7 months. Mean baseline c-LDL was 102.9 mg/dL and eGFR was 49 mL/min/m2. In the 3rd month after starting the treatment, we observed a reduction in cholesterol and c-LDL (p = 0.008, p = 0.009), which was maintained at 6 months (p < 0.001, p = 0.002). However, no differences were found in triglycerides, eGFR, albuminuria and plasma immunosuppressants levels (Fig. 1). No cases of acute rejection or adverse effects were reported. In 5 patients, anti-HLA antibodies were determined as a part of their routine follow-up 6 months after the drug prescription and were negative. Conclusion In our experience, we observed good results with evolocumab, since total cholesterol and c-LDL reduced rapidly after starting the treatment. Furthermore, renal function maintained stable, no change in proteinuria and no other safety concerns were reported. In our case, neither tacrolimus nor everolimus trough levels remained unchanged and no immunological adverse outcomes were notified. More studies in this population and with longer follow-up are needed to assess the benefit on KT recipients and graft survival.

LDL cholesterol target attainment in cardiovascular high- and very-high-risk patients with statin intolerance: a simulation study

The inability to tolerate sufficient doses of statins, statin intolerance (SI), contributes to the non-achievement of guideline-recommended low-density lipoprotein cholesterol (LDL-C) treatment targets. Patients with SI require alternative lipid-lowering therapies (LLT). We conducted a simulation study on LDL-C target achievement with oral LLT (ezetimibe, bempedoic acid) in patients with SI, using representative data of 2.06 million German outpatients. SI was defined using literature-informed definitions based on electronic medical records (EMR). Among n = 130,778 patients with hypercholesterolaemia, available LDL-C measurement, and high or very-high cardiovascular risk, 8.6% met the definition of SI. Among patients with SI, 7.7% achieved the LDL-C target at baseline. After simulation of the stepwise addition of treatment with ezetimibe and bempedoic acid, 22.6 and 52.0% achieved the LDL-C target, respectively. The median achieved LDL-C was 80 and 62 mg/dL, the corresponding reductions from baseline were 20.0 and 38.0%, respectively. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1 vs. 49.9%). In conclusion, in patients with increased cardiovascular risk meeting the definition of SI based on EMR, combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Global cardiovascular risk, COVID-19 severity and post-COVID-19 syndrome: a clinical study.

Post-COVID-19 is a syndrome defined by signs and symptoms present until 12 weeks after COVID-19, lasting for more than 8 weeks, not explained by an alternative diagnosis. The present study aimed to assess whether the cardiovascular risk (CVR) of patients with COVID-19 correlates with symptoms and changes in respiratory function parameters in post-COVID-19. The association between CVR and the severity of acute disease was also considered. Between 21/04/21-01/09/21, we enrolled 1,782 consecutive patients with COVID-19. We divided these subjects into (i) 4 levels, based on the severity of COVID-19 (home care; hospitalized/no oxygen therapy; hospitalized/oxygen therapy; hospitalized/NIV-ICU), (ii) 2 levels, according to CVR calculated with the European Society of Cardiology SCORE tables (low-intermediate risk; high or very high risk). All subjects underwent a 3-month follow-up considering post-COVID-19 symptoms. In post-COVID-19 patients, high or very-high CVR was associated with (i) increased risk of hospitalization for COVID-19 (p<0.0001), (ii) higher prevalence of severe clinical manifestations and ICU admission (p<0.0001), (iii) development of post-COVID-19 (p<0.0001) and (iv) increased risk of a larger post-COVID-19 burden of disease. We found a statistically significant association between CVR, severity of COVID-19, and post-COVID-19 syndrome three months after the end of acute disease.

LDL cholesterol target attainment in a representative German cohort of high- and very-high-CV risk patients with statin intolerance: a simulation study

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. Reasons include the inability to tolerate sufficient doses of statins. To reduce cardiovascular risk in these patients, alternative lipid-lowering therapies (LLT) are required. Purpose Simulation of LDL-C target attainment and achievable LDL-C reductions with oral LLT including ezetimibe and bempedoic acid in patients with statin intolerance (SI) using electronic health records. Methods Data were obtained from the IQVIATM Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high cardiovascular risk based on ESC/EAS guidelines and diagnosed hypercholesterolaemia. Within this cohort, statin-intolerant patients were classified by applying the following literature-informed definitions pointing towards SI with high confidence (among others): patients with LLT only consisting of non-statins, long-term discontinuation of statin therapy, down-titration of statins, and documented side effects in the electronic health records. We used a Monte Carlo approach to simulate sequentially escalating oral LLT, by adding ezetimibe and bempedoic acid in patients with uncontrolled LDL-C in this population. Results Of the total study population (n=130,778 patients), 33.9% had high and 66.1% had very-high cardiovascular risk. Within this cohort, 11,286 patients (8.6%) met the criteria of SI. Compared to the total study population, in the SI group, there were higher proportions of patients who exhibited atherosclerotic manifestations and who were classified as "very-high cardiovascular risk" (73.7% vs. 66.1%). Their LDL-C levels were slightly higher (105.6 vs. 103.6 mg/dL). 46.5% received a low-intensity statin monotherapy. Ezetimibe, both as monotherapy or in combination, was more frequently prescribed. 12.3% did not receive any LLT (Table). Patients classified as statin-intolerant entered into the simulation model. At baseline, 7.7% were at LDL-C target. In patients without ezetimibe, consecutive treatment with ezetimibe and bempedoic acid increased the calculated proportion of patients at goal to 22.6% and 52.0%. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1% vs. 49.9%). The median LDL-C (IQR) after simulation of ezetimibe and bempedoic acid treatment was 62 (48–84) mg/dL (Figure). Conclusions Patients meeting the definition of SI based on their electronic health records represented 8.6% of the total cohort of the patients with high or very-high cardiovascular risk. In this population, oral combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial

Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8mmol/L or non-FH patients with screening LDL-C level ≥3.4mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450mg Q4W, tafolecimab 600mg Q6W, placebo 450mg Q4W, or placebo 600mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n=411) or placebo (n=203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]:-65.0% [97.5% CI:-70.2%,-59.9%] for 450mg Q4W;-57.3% [97.5% CI:-64.0%,-50.7%] for 600mg Q6W; both P<0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8mmol/L, and LDL-C < 1.4mmol/L than placebo group at both dose regimens (all P<0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Tafolecimab dosed at 450mg Q4W and 600mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. This study was sponsored by Innovent Biologics, Inc.

Application of EULAR and European Society of Cardiology recommendations with regard to blood pressure and lipid management in antiphospholipid syndrome

BackgroundTo examine blood pressure (BP) and lipid treatment eligibility in antiphospholipid syndrome (APS) according to European Alliance of Associations for Rheumatology (EULAR) and European Society of Cardiology (ESC) recommendations.MethodsSystematic Coronary...

A real-world analysis of adherence and biochemical outcome of patients on rosuvastatin/ezetimibe free vs single-pill combination in italy

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Servier. Background/Introduction One of the most effective strategies for cardiovascular (CV) disease prevention is lipid level control. To achieve this control, a satisfactory level of adherence to effective lipid-lowering medications is required. Purpose To evaluate and compare medication adherence and plasma levels of low-density lipoprotein cholesterol (LDL-C) among 2 cohorts of patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free (FC) or single-pill combination (SPC), in an Italian real-world setting. Methods A retrospective analysis was performed using administrative databases linked to laboratory database, covering approximately 7 million health-assisted subjects. Adults prescribed with ROS/EZE as SPC or FC during January 2018-June 2020 were included and categorized in 2 cohorts. Index date (ID) was the first prescription of SPC or first simultaneous prescription of the 2 drugs (within 30 days interval). Patients were characterized during all available periods prior to ID and followed-up to end of data availability. Propensity score matching (PSM) was applied to minimize selection bias between cohorts; adherence was calculated as proportion of days covered (PDC): PDC&amp;lt;25% non-adherence; PDC=25-75% partial adherence; PDC&amp;gt;75% adherence, after PSM. Based on ESC/EAS 2019 guidelines, patients were stratified by CV risk profile. For a subgroup of patients (n=3,846) with plasma-LDL-C data availability (at ID and during first year of follow-up), the percentages of patients being above 55 mg/dl LDL-C for very-high risk, 70 mg/dl for high risk, and 116 mg/dl for other CV risk patients, and who reached these levels during follow-up were reported. Results The analysis included 25,886 patients in SPC cohort and 7,309 in FC. Post-PSM cohorts were balanced for their characteristics, including CV risk, and comprised 21,927 (SPC) and 7,309 (FC) patients. A higher percentage of patients were adherent to SPC vs FC (56.8% vs 44.5%, p&amp;lt;0.001). A lower percentage of non-adherent patients was found for the SPC vs FC (12.6% vs 27.4%, p&amp;lt;0.001). Among very-high, high and other CV risk patients, respectively, a 30%, 28% and 21% increase in the number of adherent patients was found for SPC vs FC [65.4% vs 50.4%, p&amp;lt;0.001 (very-high); 54.7% vs 42.7%, p&amp;lt;0.001 (high); 43.5% vs 35.9%, p&amp;lt;0.001 (other CV risk)] (Fig. 1). The proportion of very-high-CV risk patients reaching LDL-C ≤55mg/dl in the first year of follow-up was higher in SPC vs FC (35.4% vs 23.8%, p&amp;lt;0.001) (Fig.2). Similarly, among high-risk patients, 46.9% and 23.1% (p&amp;lt;0.001) of SPC and FC, respectively, reached ≤70 mg/dl LDL-C and among other CV-risk patients, 71.6% and 49.5% (p&amp;lt;0.001) of SPC and FC, respectively, reached ≤116 mg/dl LDL-C levels during first year of follow-up. Conclusions This real-world analysis in patients with hypercholesterolemia showed that treatment with ROS/EZE SPC vs FC could be associated with better medication adherence and lower LDL-C levels, whatever the CV risk category.

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT)

Background and aimsProprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. MethodsAll data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. Results798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. ConclusionsPCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.

HSD14 Lacking Observance of the Guidelines on Dyslipidaemias as Possible Reason for Low LDL-C Goal Attainment in Patients at High and Very High Cardiovascular Risk

Several studies have clearly demonstrated the causative role of increased plasma concentrations of LDL-C in the process of atherosclerotic plaque formation. These findings have been reflected in the updated guidelines for the management of dyslipidaemias, proposing new stringent LDL-C goals and treatment algorithm. Although the evidence is quickly translated into the guidelines, there still exists a large gap between recommendations and real clinical practice. The objective of the study was to investigate the adherence of Czech cardiologists to the dyslipidaemias guidelines, especially in the management of patients with high- and very-high cardiovascular risk.

Abstract 10111: Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

Introduction: Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285). Methods: Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L. Results: A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L compared with corresponding placebo groups ( Table ). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia. Conclusions: Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.

Simulation study on LDL cholesterol target attainment, treatment costs, and ASCVD events with bempedoic acid in patients at high and very-high cardiovascular risk.

Background and aimsThe LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. The study objective was to estimate the impact of bempedoic acid treatment on LDL-C target attainment, drug costs, and atherosclerotic cardiovascular disease (ASCVD) events.The simulation used a Monte Carlo approach in a representative cohort of German outpatients at high or very-high cardiovascular risk. Additionally to statins, consecutive treatment with ezetimibe, bempedoic acid, and a PCSK9 inhibitor was simulated in patients not achieving their LDL-C goal. Considered were scenarios without and with bempedoic acid (where bempedoic acid was replaced by a PCSK9 inhibitor when LDL-C was not controlled).ResultsThe simulation cohort consisted of 105,577 patients, of whom 76,900 had very-high and 28,677 high cardiovascular risk. At baseline, 11.2% of patients achieved their risk-based LDL-C target. Sequential addition of ezetimibe and bempedoic acid resulted in target LDL-C in 33.1% and 61.9%, respectively. Treatment with bempedoic acid reduced the need for a PCSK9 inhibitor from 66.6% to 37.8% and reduced drug costs by 35.9% per year on stable lipid-lowering medication. Compared to using only statins and ezetimibe, this approach is projected to prevent additional 6,148 ASCVD events annually per 1 million patients, whereas PCSK9 inhibition alone would prevent 7,939 additional ASCVD events annually.ConclusionsA considerably larger proportion of cardiovascular high- and very-high-risk patients can achieve guideline-recommended LDL-C goals with escalated lipid-lowering medication. Bempedoic acid is projected to substantially decrease the need for PCSK9 inhibitor treatment to achieve LDL-C targets, associated with reduced drug costs albeit with fewer prevented events.

Simulation study on LDL cholesterol target attainment, ASCVD events, and treatment cost of bempedoic acid in a representative German cohort of high- and very-high-CV risk patients

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. For patients above goal despite statins and ezetimibe, additional LDL-C lowering can be achieved by treatment with bempedoic acid (BA) or PCSK9 inhibitors (PCSK9i). Purpose Simulation of LDL-C target attainment with BA as additional lipid-lowering medication in a representative cohort of German outpatients at high or very-high cardiovascular (CV) risk, calculation of the number of prevented atherosclerotic cardiovascular disease (ASCVD) events and budget impact. Methods Data were obtained from IQVIA™ Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high CV risk (based on ESC/EAS guidelines), diagnosed hypercholesterolaemia and treatment with lipid-lowering medication. In patients with uncontrolled LDL-C, sequentially adding ezetimibe and BA was simulated using a Monte Carlo approach. Drug costs to control LDL-C by adding BA vs. PCSK9i were calculated based on current pricing in Germany. Considered were a scenario without BA and one with BA, in which BA was replaced by PCSK9i if LDL-C was still not controlled. The number of prevented events was calculated based on simulated LDL-C reduction. Results 105,577 patients met the inclusion criteria and entered the simulation model. 76,900 patients had very-high and 28,677 high CV risk. The baseline characteristics are depicted in Table 1. Only a minority of total patients (11.2%) achieved their risk-based LDL-C goal. Simulation of the sequential addition of ezetimibe to statins resulted in controlled LDL-C in 33.1% of total patients. Simulated addition of BA in patients with uncontrolled LDL-C despite statin and ezetimibe increased the percentage of controlled patients to 61.9% of total. The proportion of patients achieving LDL-C goals was higher in high- compared to very-high risk patients (Figure 1). Treatment with BA reduced the need for PCSK9i in patients on statin and ezetimibe from 66.6% to 37.8%. The considered scenario resulted in an anticipated reduction of drug costs by 35.9% per year on stable lipid-lowering medication. This effect was more pronounced in high-risk compared to very-high-risk patients (cost reductions of 40.6% and 34.4%, respectively). In this simulation model, the BA/PCSK9i strategy is projected to prevent 6,148 ASCVD events annually per 1 million patients on top of statin+ezetimibe, whereas LDL-C target achievement with PCSK9i alone would prevent 7,939 events. Conclusions A considerable larger proportion of high- and very-high-risk patients can achieve guideline-recommended LDL-C targets with escalated lipid-lowering medication. BA is projected to substantially decrease the need for PCSK9i treatment to achieve LDL-C targets which reduces drug costs compared to PCSK9i. LDL-C target attainment is projected to markedly reduce ASCVD events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Deutschland GmbH

Cardiovascular risk factors in patients with and without a history of atherosclerotic cardiovascular disease in the SANTORINI study and estimation of risk

Abstract 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

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 &amp;lt;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

Prevalence and outcomes of peripheral artery disease in a real-world cohort of patients with acute coronary syndrome: insights from the prospective SPUM registry

Abstract Background Despite substantial improvement in secondary preventive therapy, the burden of recurrent cardiovascular (CV) events remains high. Peripheral artery disease (PAD), is a potential marker of increased residual ischemic risk in acute coronary syndrome (ACS) patients suggesting greater net clinical benefit from intensified individualized therapy. Purpose We aimed to assess the prevalence and cardiovascular (CV) outcomes of peripheral arterial disease (PAD) in 4'787 patients with acute coronary syndromes (ACS) in the Swiss prospective multicenter SPUM study. Methods PAD was defined according to international guidelines. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), i.e., stroke, myocardial infarction (MI) and death at 1 year. Adjusted Cox proportional hazards regression models were used to estimate the risk associated with PAD and outcomes. Results Out of 4'787 ACS patients, 285 patients (6.0%) had PAD. These patients were older (70.1±10.6 vs 63.3±12.4, p&amp;lt;0.001), presented all traditional CV risk factors (all p&amp;lt;0.001) and were more likely to have a complex history of CV disease, such as previous MI (24.3% vs 11.4%, p&amp;lt;0.001), prior percutaneous (32.3% vs 13.8%, p&amp;lt;0.001) or surgical (12.6% vs 3.5%, p&amp;lt;0.001) coronary revascularization. PAD-patients presented also higher levels of inflammatory biomarkers, such as hs-CRP, and GRACE 2.0 score (all p&amp;lt;0.001). At 1 year, patients with PAD had a higher rate of MACCE compared to those presenting without PAD. Rates of the individual components of the primary endpoint and CV-death were all significantly higher in patients with PAD (all p&amp;lt;0.001), except for a numerical increase in MI (5.3% vs 3.3%, p=0.060). This enhanced risk persisted after adjustment for differences in baseline characteristics, with a 53% (Adj. HR 1.53, CI95% 1.14–2.08, p=0.005) increase in MACCE. In spite of high-intensity anti-thrombotic therapy, PAD patients presented the same rate (Adj. HR 1.03, CI95% 0.68–1.54, p=0.901) of major bleeding events at 1 year. Conclusions Among a real-world cohort of ACS patients, the coexistence of PAD, a very-high CV risk phenotype, is associated with significantly increased rates of MACCE, but no difference in major bleeding events. These observations might help clinicians to further stratify this very-high risk population and to identify patients who may derive the greatest benefit from more intense secondary prevention therapies. Funding Acknowledgement Type of funding sources: None.

The challenge of lipid-modifying therapies in the achievement of optimal LDL-C levels in high and very high CV risk patients: Still an open question

Background and Aims : Hypercholesterolemia is one of the main modifiable atherosclerotic cardiovascular (CV) disease’s risk factors. The aim was to evaluate the efficacy of the currently available lipid lowering therapy (LLT) and the achievement of treatment targets (TT) in a cohort of high and very-high CV risk patients treated with maximum tolerated LLT.

Current lipid-lowering approach and LDL target achievement in very high-risk patients: in-hospital results of a high-volume primary percutaneous coronary intervention tertiary center

Abstract Funding Acknowledgements Type of funding sources: None. Background Low-density lipoprotein-cholesterol (LDL-C) is a well-accepted causal risk factor for atherothrombotic cardiovascular disease. Several randomized controlled trials and meta-analyses have shown that lipid-lowering therapies reduce cardiovascular events and have a positive effect in reducing vulnerable plaques. In particular, the recommended target for LDL-C has become more and more stringent, moving to 1.4 mmol/l (55 mg/dl) for very high-risk patients. According to the 2019 ESC/EAS Guidelines, the current paradigm for lipid management favors a stepwise approach consisting of early initiation of high-intensity statin, followed by subsequent addition of ezetimibe, and ultimately a consideration of PCSK9 inhibitor treatment if LDL-C levels remain elevated. Methods We recruited 307 patients admitted for acute coronary syndrome (ACS) during the COVID-19 pandemic from March 2020 to December 2020. Baseline LDL-C concentration and prescribed hypolipemiant treatment at hospital admission and discharge were registered. Therefore, we included all consecutive patients identified as very-high cardiovascular risk, according to 2019 ESC guidelines. We stratified our population through variables independently associated with non-attainment of LDL-cholesterol such as hypertension, diabetes, peripheral arterial disease, clinical manifestations of ACS, number of main vessels treated, and complexity of the atherosclerotic disease. Results 274 patients were included. Mean age was 69,9 years (SD 11,4), 20,8 % were women, 23,7 % had diabetes, 16,4 % had PAD and 32,1 % suffered from valvular disease, mainly with mitral regurgitation or aortic stenosis no more than mild or moderate. Of 25.1% with a previous history of acute myocardial infarction, the 33,3% of whom didn’t have statin therapy pre-ACS index (p =0,001). At admission, medium cholesterol levels of patients that underwent previous coronary revascularization (25,5% of the total population) were 84,21 ± 31,2 mg/dL, not in range according to both 2016 and 2019 ESC guidelines. At discharge, 77,37 % of all the patients included received only statin therapy VS 22,63% with statin plus ezetimibe. In the subpopulation of patients with recurring ACS events with LDL pre-admission &amp;gt; 100 mg/dL,despite high dose statin, only 25% of this population were discharged adding ezetimibe (VS 75% who kept on the treatment of high dose statin without up-titration). Conclusions Management of dyslipidemia is frequently suboptimal and the gap between guidelines and clinical practice for lipid management across Europe has been exacerbated by the 2019 guidelines. A greater utilization of non-statin lipid-lowering therapies is likely needed to reach the LDL-C optimal target. A correct stratification of the risk class would help to identify, in a personalized perspective of treatment, patients at very high risk that would take advantage of more aggressive therapy to reach the lowest target of LDL-C ("the lower is better").

MO731: Predictors of Early and 1-Year Mortality After an Acute Coronary Event in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) is the leading cause of mortality in haemodialysis (HD) patients (40%), mainly secondary to a coronary event (17%). According to the European Society of Cardiology (ESC), beta-blockers (BBs), anti-platelets, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and statins are the cornerstones of CVD prevention. However, a great percentage of dialysis patients remain undermedicated. Our aim is to identify the predictors of mortality in HD patients after an acute myocardial infarction (AMI) during hospitalization and 1 year after the cardiac event. Methods We performed an observational retrospective study of all HD patients admitted to the coronary intensive care unit between January 2017 and December 2020 due to a myocardial infarction. Our variables of interest were collected before and after hospital discharge and 1 year after. We assessed patients’ frailty using the clinical frailty scale (CFS) and baseline cardiovascular (CV) risk using ESC’s classification; as we focused in HD patients (very-high risk of CVD), we classified CV risk regardless of the kidney disease. IBM SPSS 23.0 was used to perform statistical analysis; the confidence interval (CI) was set at 95%. RESULTS We collected 70 patients (males: n = 51, 73.2%), with a mean age of 70.9 ± 12.2 years and a median time in HD of 73.2 ± 60 months. Identifiable CV risk factors were: dyslipidaemia (98.6%), arterial hypertension (95.7%), heart failure (74.3%), diabetes (57.1%) and obesity (55.7%); mean total cholesterol and low-density lipoprotein cholesterol (LDL) levels were 151 ± 39.6 and 97.5 ± 34.1 mg/dL, respectively. As a result, 81.4% of our sample was classified as having a very high baseline CV risk. Before admission, most patients were on statin therapy (87.1%), but only 34.2% were taking the proper statin class/dosage adjusted to their CV risk. In fact, only 7.1% were previously medicated with all prognosis-modifying drugs (ACEis/ARBs, statins, anti-platelets and BBs). The mean hospitalization stay was 10.3 ± 9 days, and the early mortality rate (30 days post-admission) was 18.6%. Mortality was higher in older patients (72.5 ± 10.3 versus 69.1 ± 10.9 years; P = .3), males (21.6 versus 10.5%), with longer HD vintage (82.8 ± 46.8 versus 70.8 ± 48 months; P = 0.41) and higher CV risk (very-high CV risk, 84.6 versus 80%; P = .7); hypoalbuminemia (serum albumin &amp;lt; 3.0 g/dL) (OR 5.4, 95% CI 1.2–25.1; P = .028) and higher frailty score (CFS ≥ 4) (OR 6.1, 95% CI 1.2–30.0; P = .002) prompt a worse short-term prognosis. The mortality rate after 1 year was 30%, with a median time of 5.6 ± 2.4 months since the cardiac event. Mortality was also higher in older patients (71.5 ± 10 versus 69 ± 10 years; P = .34), males (31.3 versus 26.3%; P = 0.70), with longer dialysis vintage (85.2 ± 45.6 versus 67.2 ± 48; P = .14) and longer hospitalizations (12.8 ± 9.9 versus 9.3 ± 8.3; P = .12). After discharge, patients prescribed with at least three prognosis-modifying drugs had a lower 1-year mortality rate (3.2 versus 26.9%; OR 11, 95% CI 1.2–97.0; P = .003). Hypoalbuminemia (OR 9.4, 95% CI 2.3–4.3’; P = .002) and higher frailty scores (CFS ≥ 4) (OR 4.1, 95% CI 1.2–14.0; P = .025) were associated with worse outcomes. CONCLUSION We concluded that most HD patients were undermedicated prior to a coronary event given their baseline CV risk. Despite most studies in HD patients did not find a beneficial long-term effect of starting statin therapy after HD initiation, one must always individualize therapy according to the patient's CV risk. In our series, better-nourished patients with at least three prognosis-modifying drugs had a lower mortality rate, which highlights the importance of these drugs on survival together with optimal nutritional care.

Effect of PCSK9 Inhibitor on Blood Lipid Levels in Patients with High and Very-High CVD Risk: A Systematic Review and Meta-Analysis

Objectives We aimed to investigate the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on blood lipid levels in patients with high and very-high cardiovascular risk. Design 14 trials (n = 52,586 patients) comparing treatment with or without PCSK9 inhibitors were retrieved from PubMed and Embase updated to 1st Jun 2021. The data quality of included studies was assessed by two independent researchers using the Cochrane systematic review method. All-cause mortality, cardiovascular mortality, and changes in serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), apolipoprotein B (ApoB), lipoprotein (a) (LP (a)), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A1 (ApoA1) from baseline were analyzed using Rev Man 5.1.0 software. Results Compared with treatments without PCSK9 inhibitor, addition of PCSK9 inhibitors (evolocumab and alirocumab) had obvious decreasing effects on the levels of LDL-C [MD = −46.86, 95% CI (−54.99 to −38.72), P < 0.00001], TC [MD = −31.92, 95% CI (−39.47 to −24.38), P < 0.00001], TG [MD = −8.13, 95% CI (−10.48 to −5.79), P < 0.00001], LP(a) [MD = −26.69, 95% CI (-27.93 to −25.44), P < 0.00001], non-HDL-C [MD = −42.86, 95% CI (−45.81 to −39.92), P < 0.00001], and ApoB [MD = −38.44, 95% CI (−42.23 to -34.65), P < 0.00001] in high CVD risk patients. Conversely, changes of HDL-C [MD = 6.27, CI (5.17 to 7.36), P < 0.00001] and ApoA1 [MD = 4.33, 95% CI (3.53 to 5.13), P < 0.00001] from baseline were significantly more in high cardiovascular disease risk patients who received PCSK9 inhibitors treatment. Conclusion Addition of PCSK9 inhibitors to standard therapy resulted in definite improvement in blood lipid levels compared with therapies that did not include them.

Combination therapy in the guidelines: from high-intensity statins to high-intensity lipid-lowering therapies

The causal role of cholesterol in atherosclerosis was established more than 100 years ago. Along with the fact that the higher the cholesterol, the greater the risk of atherosclerotic cardiovascular diseases (ASCVD), many randomized controlled trials (RCT) have shown that lowering LDL cholesterol (LDL-C) is associated with a lower incidence of ASCVD. This impact of lipid-lowering therapies on cardiovascular risk is independent of the drug used, as shown by several meta-analyses and Mendelian randomization studies. Therefore, the concept of using “high-intensity statins” should be changed to “high-intensity lipid-lowering therapies” that go beyond the use of statins. Recent RCTs using non-statin lipid-lowering therapies has provided scientific evidence that the lower the LDL-C, the better in terms of cardiovascular events. Based on these observations, current guidelines recommend achieving very low LDL-C levels in patients with high and very-high cardiovascular risk. To achieve these demanding goals, the physician must use the full spectrum of lipid-lowering therapies, beyond high-intensity, high-dose statins. Oral combination therapies and, when necessary, subcutaneous treatments become the new standard of care for hypercholesterolemia. However, the number of patients achieving LDL-C goals is unacceptably low. This is due in part to insufficient prescription and insufficient treatment. To improve the efficacy of therapy, several strategies have been proposed, step by step, planning therapy and maximizing treatment, based on the needs of the patient. A wider use of lipid-lowering