Abstract 4138757: Lipid-Lowering Therapy Intensification and Low-Density Lipoprotein Cholesterol Testing Following a Major Cardiovascular Event or Procedure in Adult Patients in the United States

Background Optimizing low-density lipoprotein cholesterol (LDL-C) is crucial for both primary and secondary prevention in atherosclerotic cardiovascular disease (ASCVD). Clinical guidelines for managing LDL-C recommend lower targets with increasing patient risk level and consideration of appropriate intensification of lipid lowering therapy (LLT). Understanding trends in LLT use can help inform clinical practice and health policy. This study analysed long-term trends in LLT use among patients with ASCVD among the general population within the Maccabi Health Services (MHS, a nationwide payer-provider health plan in Israel, representing one quarter of the population) database. Methods We retrospectively examined deidentified electronic health records and pharmacy data from MHS between 2013 and 2023. We included adults aged 40–79 years with a first non-fatal ASCVD event between January 2006 and December 2023 and assessed annual LLT utilization patterns following index event. Using multivariable logistic regression, we identified factors independently associated with stable LLT utilization at 1, 3, 5, and 8 years of follow-up among patients who experienced their first event in 2013 or later and survived for the corresponding duration. Stable LLT utilization was proxied as the purchase of at least one LLT of any type in each follow-up year. Results Among 44,410 adults experiencing their first ASCVD event, approximately 86% were on any LLT in any of the follow-up years. Among them, we observed a significant decrease in the use of statin monotherapy and increase in combination use of statins and ezetimibe between 2013 and 2023, dropping from 76% to 49% and rising from 4.3% in 2013 to 31.6% in 2023, respectively (p<0.001, Figure 1). The utilization of PCSK9 inhibitors has also grown steadily, from 0.02% in 2016 to 3.15% in 2023, mostly in combination with other LLTs. Across all subgroups, consistent LLT use was independently associated (Figure 2) with male sex, higher socioeconomic status (SES), an index event of an MI (compared to ischemic stroke, PAD or carotid endarterectomy), a history of diabetes, hypertension, or LLT use prior to their index event. Younger age was independently associated with less LLT use. Conclusions We observed steady overall LLT use and increasing combination LLT use over the last decade among patients in MHS following an ASCVD event. Observations underscore the need to target certain groups of patients in guideline directed LLT use following ASCVD events, particularly among the younger population, women, those with lower SES, and those experiencing ischemic stroke or PAD. Targeted, innovative interventions may be needed to address barriers to, continued implementation of, and adherence to, guideline recommended LLT. Further research is warranted to explore the underlying causes of LLT non-utilization and develop effective strategies to mitigate this challenge.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Strategies that lower LDL-C levels reduce this risk. Hypothesis: We hypothesized that real-world PAD patients are overall undertreated with lipid lowering therapies (LLT) but that LLT use and achieved LDL-C are improved in high risk patients with ischemic events. Methods: Patients with PAD in the MarketScan database linked to PROGNOS lab data from January 1, 2014 through December 31, 2018 were examined. Outcomes included use of LLT, defined as high intensity (HI) (high intensity statin, any statin plus ezetimibe, or any use of a PCSK9 inhibitor), low intensity (LI) (any other lipid regimen), or no therapy, and follow up LDL-C level. Goal LDL-C was defined as <70 mg/dl. Results: Among 18,747 PAD patients, 25% were on HI LLT, 43% were on LI LLT, and 32% were on no therapy at baseline (Figure A). The median LDL-C was 91 mg/dl (IQR 70, 118), and 25% of patients were at goal (Figure B). After a median follow up of 18 months, use of HI LLT increased by 4%, the median LDL-C decreased by 5 mg/dl, and an additional 3% of patients were at goal LDL-C. Greater use of HI LLT was observed among patients with a MACE (55%) or MALE (41%) event during follow up compared with patients without an ischemic event (26%) during follow up (Figure C). Follow up LDL-C levels remained above goal for most patients (post-MACE: median LDL-C 77 mg/dl, 42% patients at goal; post-MALE: median LDL-C 80 mg/dl, 36% patients at goal). Conclusions: In PAD patients, use of LLT is suboptimal, and LDL-C levels remain elevated. After an ischemic event, LLT use is intensified, with greater use of HI LLT observed after MACE than MALE. Despite this, LLT remains underutilized, with >50% of patients not at goal LDL-C. Strategies to better implement proven therapies to reduce risk in this high risk population are needed.

It is unclear how the type of an atherosclerotic cardiovascular disease (ASCVD) event potentially influences patients' likelihood of smoking cessation. Using 2013 to 2018 data from the US based National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient cardiac registry, we identified patients who were current smokers at a clinic visit and followed them over time for a subsequent ASCVD event. Self-reported smoking status was assessed at each consecutive visit and used to determine smoking cessation after each interim ASCVD event (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke/transient ischemic attack, peripheral artery disease). We constructed separate multivariable Cox models with nonproportional hazards to examine the association of each interim ASCVD event with smoking cessation, compared with not having an interim ASCVD event. We estimated the relative association of ASCVD event type with smoking cessation using contrast tests. Analyses were stratified by presence versus absence of ASCVD at baseline. Across 530 cardiology practices, we identified 1 933 283 current smokers (mean age 62±15, male 54%, ASCVD at baseline 50%). Among the 322 743 patients who had an interim ASCVD event and were still smoking, 41 336 (12.8%) quit smoking by their first subsequent clinic visit, which was higher among those with baseline ASCVD (13.4%) as compared with those without baseline ASCVD (11.5%). Each type of ASCVD event was associated with an increased likelihood of smoking. Patients who had an myocardial infarction, underwent coronary artery bypass graft (hazard ratio, 1.60 [95% CI, 1.55-1.65]), or had a stroke or transient ischemic attack were more likely to quit smoking as compared with those who underwent elective percutaneous coronary intervention or had a new diagnosis of peripheral artery disease (hazard ratio, 1.20 [95% CI, 1.17-1.22]). Only 13% of patients reported smoking cessation after an ASCVD event, with the type of event being associated with the likelihood of smoking cessation, prompting the need for patient-centered interventions.

Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: An analysis of 65,396 hospitalizations from 344 hospitals participating in Get With The Guidelines (GWTG)

Background People living with Human Immunodeficiency Virus (PLWHIV) under antiretrovirals have an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. The risk factors associated with ASCVD events in this high risk population are various including traditional vascular risk factors and specific HIV-related factors. However their respective influence is questionable. Purpose Our aim was to determine the incidence of ASCVD events in a large cohort of PLWHIV and to identify the risk factors associated. Methods We conducted a longitudinal observational cohort study of asymptomatic PLWHIV at high risk of ASCVD addressed to our preventive cardiovascular unit for non-invasive cardiovascular evaluation. The first ASCVD event was censored and included CV death, acute coronary syndromes, coronary and peripheral revascularizations (PCI or CABG or endarterectomy or limb procedures) and ischemic strokes. Results From January 2003 to December 2014, 763 consecutive asymptomatic PLWHIV were enrolled (mean age of 51.3±8.3 years, 87% men, 90% were free of known coronary artery disease, mean Left ventricular ejection fraction 60%). At baseline, traditional CV risk factors were as follow: 54% had dyslipidemia, 43% hypertension, 35% were active smokers, 22% had family history of CAD and 11% were diabetics. Statins were prescribed in 38% of the cohort, aspirin in 14%, clopidogrel in 14% betablockers in 14%, RAS blockers in 32%, Calcium channel blockers in 8%. At baseline, median duration of HIV seropositivity was 19.8 years (14.0–23.6), 94% were under ARV predominantly protease inhibitors (68%). Median CD4 cell count was 545/mm3 (404–745) and 92% had undetectable HIV viral load. During a median follow up of 5.8 years (3.7–8.7), 58 (7.3%) subjects had a first ASCVD event (incidence of 12.70 [9.78–16.51] per 1000 persons-years) including 5 cardiovascular deaths, 14 ACS, 20 coronary revascularizations, 13 peripheral vascular procedures and 6 strokes) with a median time of occurrence of 3.1 years (1.5–5.1). CV death (first and second ASCVD events) occurred in 8 patients (22%) after CV death related to malignancies (33%) but before deaths related to unexplained causes (21%), infectious disease (13%), liver disease (8%) and suicides (3%). Coronary events including coronary death, MI, and coronary revascularization occurred in 39 patients (5.2%); Incidence of 8.28 [6.00–11.43] per 1000 persons-years. Conventional multivariate Cox model shows that age and tobacco were the independent risk factors associated with ACSVD events [Hazard ratio (HR) 1.04, 95% CI 0.99–1.09, p=0.05 and HR 2.17, 95% CI 1.07–4.38, p=0.03]. Conclusion Traditional vascular risk factors (age and active smoking) are associated with the occurrence of ASCVD events predominantly coronary artery disease in our observational cohort of asymptomatic PLWIHV at high risk for ASCVD. Cardiovascular prevention including tobacco cease action is mandatory in the aging HIV population.

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

Atherosclerotic cardiovascular disease (ASCVD) is highly prevalent in the US, with studies indicating substantial rates of nonadherence to and undertreatment with statin therapy. The 2013 American College of Cardiology/American Heart Association guideline recommended high-intensity statins for all patients age 75 years and younger with documented ASCVD in whom such therapy is tolerated, but there is limited evidence documenting population trends of statin use, adherence, and outcomes in the periods before and after the update to the guideline. To assess trends in the use, adherence, cost, and outcomes of statin therapy for secondary prevention in patients with different types of ASCVD between 2007 and 2016. This retrospective cohort study used data from the OptumLab Data Warehouse database containing privately insured and Medicare Advantage enrollees with demographic characteristics similar to the national US population. Participants were adult patients (age ≥21 years) who had their first ASCVD event between January 1, 2007, and December 31, 2016. Data were characterized as belonging to 3 groups: (1) cardiovascular heart disease (CHD); (2) ischemic stroke or transient ischemic attack (TIA); and (3) peripheral artery disease (PAD). Data were analyzed from July 1 to August 1, 2018. Calendar year of the initial ASCVD event. Trends in the statin use (within 30 days of discharge from hospitalization), adherence (proportion of days covered ≥80% within the first year), cost, major adverse cardiac events (1-year cumulative risk), and statin intolerance (within the first year). Of the 284 954 patients with a new ASCVD event, 128 422 (45.1%) were women; the median age was 63 years (interquartile range [IQR], 54-72 years); 207 781 (72.9%) were White. The use of statins increased from 50.3% in 2007 to 59.9% in 2016, the use of high-intensity statins increased from 25.0% to 49.2%, and the adherence increased from 58.7% to 70.5% (P < .001 for all trends). Patients with CHD were more likely to receive statins and high-intensity statins and adhere to medications than patients with ischemic stroke, TIA, or PAD despite similar observed treatment benefit. In 2016, 80.9% of patients with CHD used a statin vs 65.8% of patients with ischemic stroke or TIA and 37.5% of patients with PAD. Out-of-pocket cost per 30-day decreased from a median of $20 (interquartile range, $7.6-$31.9) in 2007 to $2 (interquartile range, $1.6-$10.0) in 2016 (P < .001) with the increasing use of generic statins (42.0% in 2007 vs 94.9% in 2016; P < .001). Major adverse cardiac events decreased from 8.9% in 2007 to 6.5% in 2016 (P < .001) whereas statin intolerance increased from 4.0% to 5.1% (P < .001). There have been modest improvements in the use, adherence, and cardiovascular outcomes over the past decade for statin therapy in patients with ASCVD, but a substantial and persistent treatment gap exists between patients with and without CHD, between men and women.

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

Introduction: Current European guidelines on cardiovascular prevention recommend lipid-lowering therapies for patients who have experienced an atherosclerotic cardiovascular disease (ASCVD) event. Objectives: This study aims to provide updated data on the prescription of lipid-lowering therapies in patients discharged after an ASCVD event and to investigate the characteristics associated with a higher likelihood of receiving such therapy following the event. Methods: Using administrative data from the Lombardy region, individuals of both sexes aged ≥40 years hospitalized for an incident ASCVD event during the first nine months of 2019 were identified. The prevalence of those receiving a prescription for lipid-lowering therapy within 90 days of the event was assessed. A multivariable logistic regression model was applied to evaluate the impact of various factors on the likelihood of initiating treatment (odds ratio [OR] and 95% confidence intervals [95%CI]). Results: In a cohort of 18,370 individuals with an incident ASCVD event, 50.70% did not receive a prescription for any lipid-lowering therapy. The likelihood of initiating therapy was higher in individuals who experienced a cardiovascular event compared to a cerebrovascular event (OR 2.94, 95%CI 2.74-3.14), in patients aged 51-60 years (OR 1.22, 95%CI 1.10-1.36, compared to 61-70 years), and in those receiving antidiabetic (OR 1.42, 95%CI 1.25-1.61) or antihypertensive therapy (OR 1.77, 95%CI 1.64-1.92). Conversely, older age (71-80 years: OR 0.70, 95%CI 0.64-0.77; &gt;80 years: OR 0.38, 95%CI 0.35-0.42), female sex (OR 0.81, 95%CI 0.75–0.87), prior exposure to antithrombotic medication (OR 0.67, 95%CI 0.60-0.73), and excessive polypharmacy (OR 0.57, 95%CI 0.49-0.66 for ≥10 medications) were associated with a lower likelihood of initiating treatment after the event. Conclusions: The study highlights a suboptimal initiation of lipid-lowering therapy in patients discharged after an ASCVD event. Additionally, the results emphasize the importance of understanding influencing factors to improve patient management in secondary prevention.

Background Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC). Purpose To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C &amp;lt;70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC. Methods VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (&amp;lt;1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated. Results Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event &amp;lt;1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of &amp;lt;70 mg/dL and &amp;lt;55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively). Conclusions Participants with ASCVD and LDL-C &amp;gt;70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.

Background: Cardiovascular disease (CVD) remains the largest cause of mortality worldwide, and will claim an estimated 20 million lives annually by 2030. For those at highest risk from CVD, lipid lowering therapies (LLT), including statins, are the mainstay of treatment. Despite the widespread use of LLTs, it remains unclear whether greater intervention is required to reduce LDL-C among those at high risk. Objectives: We examined the utilization patterns of LLTs between 2003-2012, and the proportion of LLT users with LDL&lt;70 mg/dL among those in the 4 statin benefit groups (SBGs) defined by the 2013 American College of Cardiology and the American Heart Association (ACC/AHA) guidelines. Methods: We used data from National Health and Nutrition Examination Survey (NHANES) between 2003-2012 to assess trends in LLTs use and percent of users with LDL-C&lt;70 mg/dL among adults ≥18 years old in the US population who met the criteria for the 4 SBGs. We calculated frequencies, means, and percents that were weighted using NHANES-provided population weights to obtain population estimates. We conducted linear trend tests to assess whether changes in estimates were statistically significant over time. Results: The percent of adults in the 4 SBGs who used LLTs increased from 31% to 47% (p&lt;0.001) between 2003-2012. In particular, the two SBGs with a statistically significant increase in LLTs between 2003-2012 were the group with atherosclerotic cardiovascular disease (ASCVD) (p&lt;0.001) and the group with type 2 diabetes (p=0.046). Among LLT users overall, the percent with LDL-C&lt;70 mg/dL increased from 11% in 2003-2004 to 22% in 2011-2012 (p&lt;0.001). The type 2 diabetes SBG was the only one of the 4 SBGs to have a significant improvement from 2003-2012 in the percent of LLT users with LDL-C &lt; 70 mg/dL (p=0.014). In 2011-2012, 46% of the LLT users in the type 2 diabetes SBG had an LDL-C &lt;70 mg/dL. The other 3 SBGs experienced no significant change in the percent of LLT users with LDL-C &lt; 70 mg/dL, even when there was an increase in the use of LLTs in that group. For instance, among people with ASCVD, 73% used LLTs in 2011-2012, yet only 20% of these users had LDL-C&lt;70 mg/dL. Conclusions: Despite an increase in the number of people considered at high risk by the ACC/AHA guidelines and the significant rise in LLT use between 2003-2012, few LLT users have LDL-C levels less than 70 mg/dL. With recent evidence showing that lower LDL-C levels confer the greatest decreases in risk of cardiac events, a significant treatment gap and opportunity to intensify treatment remains in the US adult population at high cardiovascular risk.

Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Background introduction Many patients, especially those at very high cardiovascular (CV) risk, do not reach low-density lipoprotein cholesterol (LDL-C) targets for at least 2 reasons: they may not receive a sufficiently intensive regimen, and/or they may not adhere to their medication. Purpose Describe demographic, clinical characteristics and treatment intensity and adherence in patients on lipid lowering therapies (LLT) following an Acute Coronary Syndrome (ACS) in France. Methods Retrospective cohort study on the PGRx (the Pharmacoepidemiologic General Research eXtension program)-ACS dataset in France, with data collected retrospective and prospectively via physicians, prescription records and patient interviews. Patients were accrued prospectively and/or retrospectively by centres from the PGRx Cardiology and General Practitioners networks. We included adult patients (≥18 years) suffering an ACS between 2013 and 2016 who received LLT at or within 92 days of their ACS hospital discharge. Follow-up was censored at time of new CV event, death, lost to follow-up or interview date (mean duration 12.4 months). Outcomes of interest included LLT intensity (high, moderate and low intensity statins with or without ezetimibe) and adherence measured as proportion of days covered (PDC). Results 2695 eligible patients were included (77% men); mean age (SD) 63.1 (12.8), 18% had diabetes mellitus, mean (SD) LDL-C 112.1 (46.4) mg/dl. Treatment with LLT at discharge is summarised in table below. Age and baseline LDL-C were drivers of treatment intensity with higher proportion of patients on high intensity statins in younger patients and in those with higher baseline LDL-C. Overall 70% of patients were adherent (PDC≥80%). Patients on moderate intensity were more adherent (76%) than those on low (63%) or high intensity statins (67%). Treatment patterns with LLT after an ACS LLT following ACS N (%) PDC at 1 year, Mean (SD) Adherent, N (%) Not Adherent, N (%) Ezetimibe 34 (1.3%) 82.8% (31.3%) 26 (76.5%) 8 (23.5%) Low intensity statins 64 (2.4%) 74.8% (33.8%) 40 (62.5%) 24 (37.5%) Moderate intensity statins 993 (37.1%) 82.0% (30.9%) 751 (75.6%) 242 (24.4%) High intensity statins 1515 (56.6%) 74.6% (36.2%) 1007 (66.5%) 508 (33.5%) Statin + ezetimibe 59 (2.2%) 75.9% (34.7%) 40 (67.8%) 19 (32.2%) Overall 2695 (100%) 77.6% (34.3%) 1871 (69.9%) 807 (30.1%) Conclusion(s) Our data show a substantial proportion of patients in France are not treated with high intensity statins after an ACS despite guidelines recommendation. Adherence to LLT is acceptable in patients after an ACS although it appears to worsen when high intense statins are used Acknowledgement/Funding Study has been funded by Amgen GmbH

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease: The Dallas Heart Study

Background and Aims Patients with chronic kidney disease (CKD) carry an extremely high burden for atherosclerotic cardiovascular disease (ASCVD), which worsens as CKD progresses. Several international guidelines, including the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, have recommended the use of lipid-lowering therapy (LLT) in this high-risk population. To evaluate the implementation of these recommendations in real-world practice, we assessed patterns of dyslipidemia management among patients with CKD. Specific objectives include describing the prevalence and intensity of LLT prescription [stratified by estimated glomerular filtration rate (GFR) and whether requiring renal replacement therapy or not] as well as adherence to guideline recommendations on LLT use. Method We conducted a single-center, cross-sectional study covering the period of January 2019 to December 2023. A review of inpatient and outpatient medical records of the Department of Medicine, University of the Philippine—Philippine General Hospital was done. Eligible patients were at least 18 years of age, and diagnosed with CKD. Exclusion criteria included having a concomitant diagnosis of Acute Kidney Injury, and being pregnant or breastfeeding at any point in the study period. Sociodemographic, clinical, and laboratory data were based off the latest entry in each patient's medical record. No clinical data were collected beyond those that were available on the records. Classification of statin intensity was based on the 2019 American Heart Association/American College of Cardiology Guidelines on the Management of Blood Cholesterol as well as the 2020 Philippine Clinical Practice Guidelines on the Management of Dyslipidemia. All analyses were descriptive and done using STATA 18. Categorical variables were summarized as frequencies and percentages. Continuous variables were reported as measures of central tendency [i.e. mean (SD) or median (IQR), as appropriate]. Results Of the 3845 patients included in the study, 2922 (76%) were prescribed LLT. The most common LLT were statins (92%), followed by statin/ezetimibe combinations (6%), then statin/fibrate combinations (2%). None were prescribed PCKS9 inhibitors, niacin, omega-3 fatty acids, or bile acid sequestrants. Among non-dialytic patients, the distribution of LLT use was as follows: a) eGFR ≥ 60 ml/min/1.73 m2: 40% (173/431) b) eGFR 30-60 ml/min/1.73 m2: 76% (1198/1576) c) eGFR &amp;lt;30 ml/min/1.73 m2: 84% (1551/1838). Among dialytic patients, 68% (601/884) were already on LLT prior to initiation of dialysis while 35% (283/884) were started on LLT after dialysis initiation. Notably, 89% (786/884) of these dialytic patients were still on moderate-to-high-intensity statin doses. Based on recommendations from the 2013 KDIGO guidelines, only 78% (2610/3334) of eligible patients were prescribed on LLT, while 61% (312/511) of ineligible patients were prescribed on LLT. Similar rates of adherence were seen to other international guideline recommendations on the management of dyslipidemia in CKD (e.g. 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol, 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemias, 2020 Clinical Practice Guidelines for the management of dyslipidemia in the Philippines). Conclusion Real-world LLT use among CKD patients remains high, even at lower eGFRs. More importantly, a large proportion of patients remain under- and over-treated, highlighting significant gaps between guideline recommendations and real-world clinical practice. Further investigation regarding the underlying reasons for these practice variations is necessary to improve quality of care, and safely reduce the burden of dyslipidemia and ASCVD among CKD patients.