Low-density Lipoprotein Cholesterol Target Achievement Research Articles

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.

Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial.

Recent changes in national and international lipid guidelines for reducing cardiovascular events recommend additional drugs, greater reductions, and lower targets for low-density lipoprotein cholesterol (LDL-C) if not attained with statins. The achievement of these targets with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has not yet been evaluated in a randomized clinical trial. To evaluate the 52-week safety and efficacy of lerodalcibep, a small anti-PCSK9-binding protein, in patients with cardiovascular disease (CVD) or who are at very high or high risk of CVD and requiring addition LDL-C-lowering treatment. This was a randomized, double-blind, placebo-controlled phase 3 trial. The trial was conducted at 66 clinics in 11 countries between April 23, 2021, and November 15, 2023. Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD were included. Patients were randomized 2:1 to monthly 1.2-mL subcutaneous lerodalcibep, 300 mg, or placebo for 52 weeks. The safety analysis included all randomized patients. The co-primary efficacy end points were percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52. Secondary efficacy outcomes included additional lipid apolipoprotein measures and achievement of guideline-recommended LDL-C targets. Of 922 randomized participants (mean [range] age, 64.5 [27-87] years; 414 [44.9%] female; mean [SD] baseline LDL-C, 116.2 [43.5] mg/dL), 811 (88%) completed the trial. The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all). With lerodalcibep, 555 of 615 participants (90%) achieved both a reduction in LDL-C of 50% or greater and recommended LDL-C targets during the study. Treatment-emergent adverse events were similar between lerodalcibep and placebo, except for injection site reactions. These occurred in 42 of 613 participants receiving lerodalcibep (6.9%) compared to 1 of 307 receiving placebo (0.3%), were graded mild or moderate, and did not result in higher discontinuation of treatment, at 26 of 613 (4.2%) and 14 of 307 (4.6%), respectively. Sporadic in vitro antidrug antibodies were detected, which had no impact on free PCSK9 or LDL-C-lowering efficacy. In this trial, lerodalcibep, a novel anti-PCSK9 small binding protein, dosed monthly and stable at ambient temperatures significantly reduced LDL-C in patients with CVD or at high risk of atherosclerotic cardiovascular disease with a safety profile similar to placebo. These results support long-term use of lerodalcibep in patients with CVD or at high risk of CVD who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone. ClinicalTrials.gov Identifier: NCT04806893.

Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75years), yet their use in very-old adults (> 75years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65years (n = 152), 65-74years (n = 104), and ≥ 75years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70mg/dL compared to patients < 65years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55mg/dL. Low LLT uptake (16%) among older adults aged 64-74years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70mg/dL and < 55mg/dL, respectively. Oldest adults (≥ 75years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases

Prescription of lipid-lowering therapy, LDLc control, and risk of MACE in patients after ST-elevation myocardial infarction in Mexico

Abstract Funding Acknowledgements None. Background/Introduction Optimal control of low-density lipoprotein cholesterol (LDLc) has been demonstrated to reduce cardiovascular event rates after ST-elevation myocardial infarction (STEMI). However, real-world data shows that a low proportion of patients achieve LDLc targets. Furthermore, the association of LDLc levels and major cardiovascular adverse events (MACE) in post-STEMI patients is limited in developing countries. Purpose In this study, we aimed to assess the prescription patterns of lipid-lowering therapies, LDLc control, and their impact on the risk of MACE after STEMI in Mexico. Methods We conducted a prospective observational study of patients with STEMI. LDLc levels and prescriptions of lipid-lowering therapy were assessed during the first scheduled visit following STEMI hospital discharge. LDLc control was determined in accordance with the 2023 European Society of Cardiology Acute Coronary Syndrome Guidelines, which recommend achieving LDLc levels below 55 mg/dL for secondary prevention. Patients were categorized as controlled (if LDLc &amp;lt;55 mg/dL) and not controlled (if LDLc &amp;gt;55 mg/dL) and were followed for a median of 4.5 years to evaluate the rate of MACE, including cardiovascular death, cardiogenic shock, recurrent MI, and heart failure. Results We included 447 patients with a mean age of 57.87 (± 10.5 years), predominantly male (84.5%). Hypertension (43.8%), smoking (41.1%), type 2 diabetes mellitus (33.5%), obesity (26.6%), and dyslipidemia (21.4%) were highly prevalent. The median LDLc level in the total population was 65.4 mg/dL (IQR 49.2- 87.7). Among these, 34% (152) were considered controlled, while 66% (295) were not. Baseline clinical characteristics did not significantly differ among the groups. Prescription of high-intensity statins reached 94.7%, and ezetimibe and PCSK-9i were used in 1.8% and 0.4% of cases, respectively. We observed no statistically significant difference (Hazard ratio: 1.03, 95% confidence interval 0.74-1.73) in the rate of MACE based on LDLc control (Fig.1). The risk of MACE was also not different based on the use of high-intensity statins. Conclusions In this real-world study of patients post-STEMI, LDLc control was achieved in just one-third of the population. While the prescription of high-intensity statins was high, combination therapy was low. We did not observe a statistically significant association with an increased long-term risk of MACE; however, we noted a higher rate of events compared with other series.

Real-world evidence evaluation of LDL-C among hospitalized patients: a population-based observational study in the timeframe 2021-2022

Aims. European registries and retrospective cohorts highlighted the lack of low-density lipoprotein-cholesterol (LDL-C) goal achievement in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause mortality and cardiovascular mortality. Aim of this study is to evaluate LDL-C levels in a Real-World setting of inpatients, identify cardiovascular risk categories and highlight treatment gaps in the implementation of LDL-C control. Methods. This retrospective, observational study included all the adult patients admitted at an Italian hospital between 2021-2022 and with LDL-C values available during hospitalization. Disease-related real-world data were collected from Hospital Information Systems using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). Assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines and lipid-lowering therapies (LLT) use were performed. Results. 13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of in-target patients was progressively lower moving towards worse categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients in VH category, in-target are 28.48%; 47.6.% in H, 69.12% in M and 68.47% in L. The impact of monotherapies and combination therapies on target achievement was also analyzed. Conclusions. This study depicts LDL-C control among an entire population of inpatients, highlighting relevant gaps especially in VH category. Future efforts must aim to reduce the cardiovascular risk of these subjects.

Temporal trends and racial/ethnic- and sex-differences in LDL cholesterol control among US adults with self-reported atherosclerotic cardiovascular disease

ObjectiveCurrent guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend targeting a low-density lipoprotein cholesterol (LDL-C) of < 70 mg/dL. However, temporal trends and racial/ethnic- and sex-differences in achievement of LDL-C targets are not well described. We assessed trends and racial/ethnic- and sex-differences in achievement of LDL-C < 70 mg/dL using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 to 2017-March 2020. MethodsWe combined NHANES cycles into 4 periods: 2005–2008, 2009–2012, 2013–2016, and 2017-March 2020 and included participants ≥ 40 years with self-reported ASCVD. We estimated LDL-C < 70 mg/dL prevalence over time and further stratified by sex and race/ethnicity. We used multivariable logistic regression adjusted for social determinants of health and clinical covariates to model LDL-C target attainment. ResultsAmong 1,826 NHANES participants representing 7,161,221 US adults with self-reported ASCVD (59.6% ≥ 65 years, 56.4% male, 74.8% White), LDL-C target attainment increased from 19.0% (95% CI, 15.3%-23.3%) in 2005–2008 to 26.3% (95% CI, 20.4%-33.1%) in 2017-March 2020 (P = 0.012 for trend). Achievement of LDL-C < 70 mg/dL significantly rose among men from19.5% (95% CI, 15.1%-24.8%) to 29.4% (95% CI, 20.7%-29.9%) without significant change in women (from 18.3% [95% CI, 13.6%-24.2%] to 22.5% [95% CI, 13.0%-35.9%]; P = 0.241 for trend). Improvement in LDL-C target attainment was similar among White, Black, and Hispanic individuals (∼5–7% increase) and was greatest among individuals of other (non-White, Hispanic, or Black) race/ethnicity (23.1% increase). In our multivariable analysis, comorbid diabetes and ages 65–75 and > 75 years were associated with LDL-C target attainment. ConclusionLDL-C control modestly improved between 2005 and 2008 and 2017-March 2020; however, only ∼1/4 of individuals met guideline-directed LDL-C treatment targets by 2017-March 2020. Women had lower LDL-C control and lesser magnitude of improvement in LDL-C control than men, highlighting a need for targeted interventions to improve lipid-lowering therapy utilization in this population.

Sex Differences in Low-Density Lipoprotein Cholesterol Treatment Among Young Israeli Patients Following Premature Acute Coronary Syndrome.

Introduction: Effective management of dyslipidemias is crucial for reducing morbidity and mortality among patients after acute coronary syndrome (ACS). Sex differences in dyslipidemia management after premature ACS in Israeli patients have not been extensively studied. This study aimed to investigate potential disparities between men and women in managing dyslipidemia, considering current guidelines. Methods: This retrospective cohort study examined patients who were 55 years old or younger and admitted to Meir Medical Center for ACS from January 2018 to February 2019. The study aimed to evaluate the use of lipid-lowering therapy (LLT), measure the achievement of target low-density lipoprotein cholesterol (LDL-C) levels, and analyze the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in both male and female patients. Results: The study included a total of 687 participants, of which 23.3% were identified as females. Upon discharge, ∼80% of the patients were prescribed high-intensity statins. After 1 year, it was observed that females had higher levels of LDL-C and lower rates of achieving target LDL-C levels (<70 and 55 mg/dL) as compared with males (45% vs. 54.6% and 30% vs. 42.2%, respectively). The use of non-statin LLT at the 1-year mark was minimal in both groups. Finally, it was found that the occurrence of MACCE was similar between males and females. Conclusion: Sex disparities in dyslipidemia management after a premature ACS were apparent, with females having higher LDL-C levels and lower rates of target achievement. Intervention is necessary to address these disparities and encourage greater use of non-statin LLT.

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.

Effectiveness of Lipid-lowering Therapy for the Secondary Prevention and Achievement of Therapeutic Goals in Atherosclerotic Cardiovascular Diseases in Accordance with the American College of Cardiology/American Heart Association 2018 Guidelines on the Management of Blood Cholesterol

Introduction: According to the India Report 2020, Kerala had the highest prevalence of atherosclerotic cardiovascular diseases (ASCVDs). Dyslipidemia is a modifiable risk factor that can prevent secondary events. American College of Cardiology/American Heart Association 2018 Guidelines for the management of blood cholesterol for secondary prevention of clinical ASCVD recommend high-intensity statins and moderate-intensity statin combination therapy for achieving target low-density lipoprotein-cholesterol (LDL-C). We conducted a study to evaluate the achievement of therapeutic goals in accordance with the guidelines in a tertiary care hospital in Kerala. Materials and Methods: Three hundred and twenty adult patients prescribed with high-intensity statin monotherapy (atorvastatin 40 mg, rosuvastatin 20 mg, and rosuvastatin 40 mg) or moderate-intensity statin combination therapy (atorvastatin 10 mg and fenofibrate 145 mg) for the secondary prevention of ASCVD event were included. Data were collected from the medical records and patient interviews. Achievement of the therapeutic goal of LDL-C ≤70 mg/dL in accordance with guidelines was evaluated and compared; the mean percentage change in LDL-C was at the baseline and after 3 months. Patients were counselled on lifestyle modifications and educated about hypolipidemic agents. Since we are aiming for secondary prevention, the patients were given appropriate counselling concerning their disease and medications they are on. Dietary lifestyle modifications were also taught. Results: One hundred and thirty-eight patients achieved the therapeutic goal, with atorvastatin 40 mg (89.37%) being the most prescribed drug, followed by rosuvastatin 20 mg (5.62%) while rosuvastatin 40 mg had a higher efficacy with mean LDL reduction 65.71 ± 15.93 at 3 months follow-up. Comparing the adherence scores before and after patient counseling, the P value was found to be &lt; 0.001, indicating it is significant. Conclusion: Lifestyle modifications and lipid-lowering therapy are crucial to tackle dyslipidemia. Poor achievement of therapeutic goals implies the need for adopting measures to improve adherence and health-related outcomes for patients with ASCVD.

Observational study of inclisiran effectiveness in Moscow healthcare

Aim. To evaluate the effectiveness of PCSK9 inhibitors (alirocumab, inclisiran and evolocumab) in patients with atherosclerotic cardiovascular disease (ASCVD) and failure to achieve the target low-density lipoprotein cholesterol (LDL-C) level for the period from November 21, 2022 to December 31, 2023.Material and methods. For the observational study, 50 patients were included in the inclisiran therapy group and 30 patients in the control group (patients with ASCVD receiving PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29)). All study participants had their anamnestic data analyzed, and initially underwent electrocardiography, echocardiography, extracranial and lower limb Doppler ultrasound, and laboratory tests (complete blood count, biochemical blood tests, lipid profile). Three medical organizations of the Moscow State Healthcare System participate in the study.Results. Interim data are presented to evaluate the effectiveness of PCSK9 targeted therapy in patients with ASCVD, obtained 3 months from the study start. The comparison groups were comparable in main clinical characteristics. When analyzing the lipid-lowering effect of inclisiran in the examined patients with ASCVD, LDL-C level significantly decreased from 2,53±0,10 mmol/l to 110±0,08 mmol/l (by 56,5%), p&lt;0,0001, while the target LDL-C level &lt;1,4 mmol/l was achieved by 77,5% of the subjects. Analysis of the lipid-lowering effect of alirocumab/evolocumab showed a significant LDL-C decrease from 2,48±0,16 mmol/l to 1,07±0,11 mmol/l (by 56,8%), p&lt;0,0001.Conclusion. The use of PCSK9 targeted therapy (alirocumab or inclisiran or evolocumab) in patients with ASCVD in Moscow make it possible to achieve target LDL-C levels, which are indicated in clinical guidelines, by 3 months.

Implementation study to introduce clinical guidelines on lipid metabolism disorders into routine practice: results of the first stage

Despite widespread knowledge in the management of patients with lipid metabolism disorders, their application in clinical practice is insufficient. Identification of barriers to the implementation of key principles of clinical guidelines in routine practice is the first step of the implementation study.Aim. To assess the organization and quality of care for patients with dyslipidemia in order to identify barriers to the implementation of the main principles of clinical guidelines in practice.Material and methods. An implementation study was planned, the initial stage of which was to conduct an anonymous online questionnaire among health care representatives of various levels in all Russian subjects.Results. The study involved 788 physicians, 124 heads of medical organizations and 48 chief freelance specialists from 84 Russian subjects. A wide range of barriers was identified: low availability of lipoprotein (a) testing (66,6% of physicians), coronary calcium index (79,4% of physicians, 71,8% of heads of a medical organizations, 79,2% of chief freelance specialists) and CT angiography (70,0% of physicians, 71,0% of heads of a medical organizations, 85,4% of chief freelance specialists). Lack of funds to manage lipid service (55,6% of heads of a medical organizations, 35,4% of chief freelance specialists). The key barrier to regular lipid-lowering therapy and achieving target low-density lipoprotein cholesterol (LDL-C) levels is lack of perceived need for treatment in patients (58,1% of physicians, 80,0% of heads of a medical organizations, 87,5% of chief freelance specialists), for PCSK9-targeted therapy — high cost (44,1% of physicians, 34,7% of heads of a medical organizations, 23,0% of chief freelance specialists). The possible fixed-dose combination therapy for dyslipidemia was positively perceived (59,7% of physicians, 42,0% of heads of a medical organizations, 35,4% of chief freelance specialists). Inclusion of innovative therapy in medicine assistance program will improve the situation in achieving target LDL-C levels (85,6% of physicians, 91,1% of heads of a medical organizations, 95,8% of chief freelance specialists).Conclusion. A wide range of barriers to the implementation of clinical guidelines on lipid metabolism disorders into practice have been identified. Based on the results obtained, the second stage of the implementation study will identify strategies aimed at eliminating the identified barriers.

Association of health information technology-driven multidisciplinary approaches with low-density lipoprotein cholesterol target achievement in patients with an acute coronary syndrome

ObjectiveControlling of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS) remains a challenge. Health information technology (HIT) is increasingly being applied to close quality gaps in chronic illness care. The aim of this study was to perform a qualitative review of the association of implementing HIT on lipid management processes of care and LDL-C goal attainment in patients with ACS. MethodEligible patients with a discharge diagnosis of ACS from January 2018 to December 2021 at a tertiary medical center were retrospectively reviewed. An HIT system with a multidisciplinary approach including initiating high-intensity statin therapy, periodic laboratory follow-up, titration of lipid-lowering agents, patient education, patient-level and system-level interventions involving database monitoring and outreach by centralized care teams was introduced in October 2018. Electronical medical records including data on medications and laboratory findings at discharge and within 1 year were compared before and after implementing the HIT system. ResultsA total of 2001 ACS patients (average age 63 ± 12.7 years, 79.66 % men) were analyzed. The LDL-C < 70 mg/dL goal attainment rates (36.52 %, 53.57 %, 59.22 %, 62.18 % in 2018–2021) and medium serum LDL-C levels (80.5 mg/dL, 68 mg/dL, 65 mg/dL, 64 mg/dL in 2018–2021) significantly improved within 6 months (2018 as the reference, all p<0.001). The LDL-C attainment rate at 12 months also steadily increased (53.80 %, 61.82 %, 64.21 % in 2019–2021, p = 0.019). Most of the patients switched to a high-intensity statins regimen at discharge (0.57 %, 63.67 %, 72.41 %, 84.44 %, in 2018–2021, p<0.001 with 2018 as the reference), with low adverse event rates. The maintenance rates of high-intensity statin regimens at 12 months continued to improve (41.36 %, 49.04 %, 61.39 % in 2019–2021, p<0.001). ConclusionsEfforts to control LDL-C should be increased in ACS patients by initiating and intensifying statin treatment earlier. Our results confirmed that a team-based strategy with HIT improved LDL-C target achievement for most patients with ACS.

Almost 1 in 2 patients with acute coronary syndrome are extremely high-risk and potential candidates for in-hospital triple lipid-lowering therapy: data from the CALLINICUS-Hellas Registry

Abstract Introduction The great heterogeneity of acute coronary syndrome (ACS) patients in the risk for cardiovascular events recurrence, prompted a recent position paper endorsed by the International Lipid Expert Panel to propose criteria, i.e. coexistence of multivessel coronary artery disease (CAD), polyvascular disease, heterozygous familial hypercholesterolemia (heFH), diabetes mellitus (DM) with estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73 m2 and/or lipoprotein (a) [Lp(a)] &amp;gt;50 mg/dL etc., which define the extremely high-risk ACS patients for whom an low-density lipoprotein cholesterol (LDL-C) &amp;lt;40 mg/dL was proposed. Purpose To estimate the proportion of patients with ACS that fulfill the criteria of the extremely high-risk group and are potential candidates for "extremely" intensive early lipid-lowering therapy (LLT) aiming at an LDL-C &amp;lt;40 mg/dL. Methods We recruited 780 consecutive patients with ACS who were participants of the CALLINICUS-Hellas Registry which is a prospective multicenter observational study that explores the adherence to LLT, the achievement of LDL-C targets and the cardiovascular events at 6- and 24-months after hospital discharge of patients with ACS. Results The prevalence of high risk components was: heFH 13.5%, multivessel CAD 44%, polyvascular disease 3.2%,and DM with eGFR &amp;lt;60 ml/min/1.73 m2 and/or Lp(a) &amp;gt;50 mg/dL 8.1%. By excluding the overlapping between these conditions, 430 ACS patients (55.1%) had at least one of the characteristics which define the extremely high-risk patients (Figure). Presuming a 65% LDL-C reduction of the levels (the pretreatment if on LLT prior admission or the admission if not on prior LLT) of the extremely high-risk ACS patients by taking a maximum dual LLT (intense statin plus ezetimibe), 312 patients, i.e., 40% of all initially recruited patients would fail to achieve an LDL-C &amp;lt;40 mg/dL suggesting that they require additional LLT, namely, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). Conclusions Almost 1 in 2 patients with ACS have extremely high-risk characteristics and are candidates for in-hospital triple LLT (statin plus ezetimibe plus PCSK9i) aiming at an LDL-C &amp;lt;40 mg/dL, a strategy shown to improve plaque stability and possibly to reduce the recurrence rate of early coronary events.Figure

Prevalence and outcomes of familial hypercholesterolemia in young patients undergoing coronary bypass surgery

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism, with elevated low-density lipoprotein cholesterol (LDL) levels and increased risk of premature coronary disease. Appropriate management substantially reduces the risk of adverse events; however, FH is frequently under-recognised and under-treated. The prevalence of FH amongst younger patients undergoing coronary bypass surgery, as well as their clinical outcomes, has not been described. Purpose This study aimed to determine the prevalence of FH in patients undergoing coronary bypass surgery prior to age 60 years. The association of FH on attainment of LDL targets and subsequent adverse cardiovascular events was also determined. Methods A retrospective analysis of all patients undergoing coronary bypass surgery prior to the age of 60 years was conducted at an Australian tertiary hospital during the period April 2008 and July 2022. Exclusion criteria were severe renal or hepatic impairment, uncontrolled malignancy, severe inflammatory or infectious disease, or lipid data unavailable. Baseline demographics and risk factors at the time of surgery were identified by a search of the Statewide Cardiothoracic Database. Blood lipid levels (highest, pre-surgery and most recent) and clinical outcomes were obtained from digital medical records. Dutch Lipid Clinic Network Scores (DLCNS) were calculated for all patients and grouped as ‘unlikely FH’ (DLCNS &amp;lt;3), ‘possible FH’ (DLCNS 3 – 5), or ‘probable / definite FH’ (DLCNS ³ 6). Attainment of LDL targets (&amp;lt;1.8mmol/L and &amp;lt;1.4mmol/L) and subsequent major adverse cardiovascular events (MACE) were compared between the ‘unlikely’ and ‘probable / definite’ FH groups. Results During the study period, 683 patients underwent coronary bypass procedures prior to the age of 60. 93 were excluded, leaving a study population of 590, with a median follow up of 7.9 years [IQR 4.7, 12.1]. Baseline characteristics are outlined in table 1. 80 patients (13.6%) were classified as ‘definite/probable FH’, 249 (42.2%) as ‘possible FH’ and 261 (44.2%) ‘unlikely FH’. As observed in table 2, patients with definite/probable FH had a significantly higher prevalence of uncontrolled lipids (81.2%) and MACE (21.3%) compared to patients with unlikely FH. For MACE, this result remained statistically significant after adjusting for age, sex, smoking status, hypertension, diabetes and surgery type (elective vs urgent) - OR 2.52 [95% CI 1.0 - 6.4]. Conclusion FH is highly prevalent in young patients undergoing coronary bypass surgery. These patients are less likely to achieve LDL targets and are more likely to suffer adverse cardiovascular events in the years following surgery. Detection of these patients may improve LDL management and clinical outcomes as well as the yield of new cases through cascade testing of close relatives.Table 1:Baseline CharacteristicsTable 2:Outcomes

Abstract 16059: Real-World Exploration of Low Density Lipoprotein Cholesterol Management in Patients With Atherosclerotic Cardiovascular Disease

Introduction: Although guidelines recommend low-density lipoprotein cholesterol (LDL-C) to bel &lt;70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), implementation of these recommendations remains low. Research Question: To understand LDL-C management nationally and identify gaps or disparities in guideline directed care. Methods: A retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance and PCORnet® was performed on patients with a LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with guideline directed LDL-C targets. Results: Among 216,074 ASCVD participants, only 86,188 (40%) had LDL-C &lt;70 mg/dL. Compared with participants with uncontrolled LDL-C (≥70mg/dL), those with LDL-C &lt;70 mg/dL tended to be male (64.9% vs 49.1%), White (87.3% vs 83.9%), had coronary artery disease (83.5% vs 73.0%), heart failure (29.1% vs 21.3%), diabetes (48.2% vs 34.1%), and atrial fibrillation (26.1% vs 19.3%). Among those with LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline (n=53,957 [41%]), only 20% were initiated on any LLT within 6 months of the elevated LDL-C value. Several factors were associated with not achieving LDL-C &lt;70 mg/dL (Figure) including female sex (RR 1.13 [95% CI 1.12-1.14] p &lt;0.001), Black race (1.15 [1.14-1.16] p &lt;0.001), and Hispanic ethnicity (1.04 [1.01-1.06] p=0.007). Additionally, prior Lp(a) testing was associated with reaching LDL-C target (0.87 [0.82-0.92], p&lt;0.001). Conclusions: Within five large U.S. health systems, only 40% of ASCVD patients achieved target LDL-C of &lt;70 mg/dL. Patients who were female, Black, and/or Hispanic were particularly unlikely to achieve target, highlighting significant disparities. Multidisciplinary and inclusive approaches from health system to community may be needed to improve LDL-C care nationally.

Effect of lipid-lowering treatment on lipid and glycemic profile of patients with elevated lipoprotein(a) levels

Aim: The evaluation of the effect of lipid-lowering treatment in patients with elevated levels of lipoprotein(a) [Lp(a)]. Material and methods: A prospective study including 70 patients with dyslipidemia and elevated Lp(a) levels (&gt;30 mg/dL) attending a Lipid Clinic in Greece. Subjects were allocated to the following therapies according to the national guidelines for cholesterol management: high-intensity statin monotherapy (S; n=28), ezetimibe added to high-intensity statin (SE; n=31), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to high-intensity statin plus ezetimibe (SEP; n=11). Follow-up duration was 3 months. We investigated the effect of these lipid-lowering interventions on participants’ lipidemic and glycemic profile. Comparisons between groups were adjusted for the baseline levels of the studied parameters. Results: Mean age was 51 ± 15 years, 40% were male, 39% were diagnosed with familial hypercholesterolaemia (FH), 16% with atherosclerotic cardiovascular disease (ASCVD), while 36%, 33% and 15% were at very high, high, and moderate cardiovascular risk, respectively. All interventions significantly reduced apolipoprotein B (apoB), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), but only PCSK9 inhibitors significantly reduced Lp(a) levels (SEP: -28% vs SE: +11% vs S: +17%, p&lt;0.05). Patients in the SE group achieved the highest rates of LDL-C target attainment (SEP: 36.4% vs SE: 12.9% vs S: 3.6% for LDL-C &lt;55 mg/dL; SEP: 36.4% vs SE: 16.1% vs S: 7.1% for LDL-C &lt;70 mg/dL, p&lt;0.05 for the comparison among groups). No significant effect on glycemic profile across treatment groups was noted. Conclusions: Add-on PCSK9 inhibitors were associated with the highest rates of LDL-C target achievement compared with high-intensity statin ± ezetimibe in high-risk patients with elevated Lp(a) and were the only class to significantly lower Lp(a) levels.

Novel therapies in clinical use for the management of hyperlipidaemia

Optimal control of low-density lipoprotein cholesterol (LDLc) is identified as a major target in reducing cardiovascular disease burden globally. However, existing lipid-lowering therapies have not been able to achieve LDLc targets even in developed countries. Therefore, novel therapies for the management of hyperlipidaemia are being trialled. Currently, there are three main groups of newer medicines; bempedoic acid, PCSK9 inhibitors and inclisiran, in addition to statins and ezetimibe in use for the management of hyperlipidaemia. This article aims to introduce these newer medicines and their clinical use in the treatment of hyperlipidaemia.

Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipid-lowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.