Lipid-lowering therapy plays a central role in reducing cardiovascular events. Over the past few decades, clinical trials utilizing several imaging techniques have consistently shown that lipid-lowering therapy can reduce the coronary plaque burden and improve plaque composition. Although intravascular ultrasound has been the most extensively used modality to assess plaque burden, other invasive modalities, such as optical coherence tomography and near-infrared spectroscopy, provide relevant data on plaque vulnerability, and computed tomography angiography detects both plaque volume and characteristics non-invasively. A large body of evidence supports the notion that reducing low-density lipoprotein cholesterol using statins combined with ezetimibe and proprotein convertase subtillisin/kexin type 9 inhibitors consistently shows improvements in plaque burden and favorable morphological changes. This review summarizes previously obtained data on the impact of lipid-lowering treatment strategies on atherosclerotic plaque regression, as assessed using several imaging modalities.

Peripheral artery disease (PAD) is a common condition characterized by atherosclerosis in the peripheral arteries, associated with concomitant coronary and cerebrovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients. This review focuses on the efficacy, safety, and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed. Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events, offering a potential treatment option for PAD patients. Safety evaluations from trials show few adverse events, most of which are injection-site reactions, indicating the overall safety profile of PCSK9 inhibitors. Clinical outcomes show a reduction in cardiovascular events, ischemic strokes, and major adverse limb events. However, despite these positive findings, PCSK9 inhibitors are still underutilized in clinical practice, possibly due to a lack of awareness among care providers and cost concerns. Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. These concepts on the level of healthcare policy not only inform reimbursements but also define the standard of care. Next, we consider the advances in atherosclerotic cardiovascular disease risk score calculators as well as evolving imaging modalities. The impact and growth of digital health, ranging from telehealth visits to online platforms and mobile applications, will also be explored. We then evaluate the ways in which machine learning and artificial intelligence-driven algorithms are being utilized to address gaps in lipid management. From an organizational perspective, we trace the redesign of medical practices to incorporate a multidisciplinary team model of care, recognizing that atherosclerotic cardiovascular disease risk is multifaceted and requires a comprehensive approach. Finally, we anticipate the future of dyslipidemia management, assessing the many ways in which atherosclerotic cardiovascular disease burden can be reduced on a population-wide scale.

Familial hypercholesterolemia (FH), a condition, which is characterized by a life-long exposure to markedly elevated low-density lipoprotein (LDL) concentrations from birth, and it still remains underdiagnosed and undertreated, despite the fact that its heterogeneous form represents one of the commonest genetic disorders to date. Indeed, only 10% of all estimated affected individuals have been diagnosed worldwide and for the most of them diagnosis comes too late, when atherosclerotic cardiovascular disease (ASCVD) has already been developed. Undiagnosed and undertreated FH leads to accelerated ASCVD with a high rate of premature deaths. Recently, several novel treatment modalities have been introduced, especially for the management of severe hypercholesterolemia. Nonetheless, a substantial number of FH patients still do not achieve guideline-recommended LDL cholesterol target values. In the present review we will summarize and critically discuss pitfalls and challenges in successful diagnosis and treatment of FH.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.

UNASSIGNED: Lipid-related risk and residual cardiovascular risk remain high in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Significant treatment gaps exist in implementation of pluripotent and effective therapies that reduce these risks.
UNASSIGNED: This study evaluates the efficacy and impact of a dedicated, standalone cardiometabolic clinic designed to address treatment gaps through streamlined management and optimization of treatment strategies.
UNASSIGNED: We retrospectively collected data from the first 400 patients with T2D and ASCVD who underwent treatment at the clinic and presented for at least one follow-up visit. These patients were primarily managed for their cardiometabolic risks and received intensified lipid-lowering therapies, including adjunct non-statin therapies.
UNASSIGNED: Significant findings included increased use of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) to 84 % and 65 %, respectively, with 94 % of patients eventually on one therapy and 55 % on dual therapy. Increases in lipid-lowering therapies led to 89 % of patients achieving low-density lipoprotein cholesterol levels below patient-specific thresholds for intensification.
UNASSIGNED: This care model effectively manages high-risk patient needs, achieving significant intensification of lipid-lowering therapies and broad use of cardiometabolic drugs, and highlights the clinic\'s potential to serve as a model for similar high-risk populations.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Reducing low-density lipoprotein cholesterol levels lowers the risk of atherosclerotic cardiovascular disease. With the current and future portfolios of emerging lipid-lowering therapies included in various national and international guidelines, the objectives of this study were (i) to investigate the perceptions of UK prescribers\', including doctors, pharmacists, and nurses, on current lipid management for cardiovascular diseases and prescriptions of novel lipid-lowering therapies, and (ii) to explore the challenges and facilitating factors of prescribing novel lipid-lowering therapies through qualitative interviews. Qualitative semi-structured interviews with twelve medical and non-medical prescribers were conducted, around 20-30 min in length. The interviews were audio-recorded and transcribed on an online platform. A thematic analysis was deployed. Four major themes emerged from the analysis: (1) prescribing barriers; (2) prescribing enablers; (3) inter-profession variability; and (4) health literacy. These themes highlighted the contrast between the need for optimal shared decision making and the various constraints in practice. Participants expressed their inexperience with novel lipid-lowering therapies and acknowledged the requirement and importance of these agents for primary cardiovascular disease prevention. Participants recognised confidence and competence as key drivers for prescribing therapies and welcomed further education and training to enhance their skillset. Patients\' misconceptions towards current lipid-lowering therapies contributed to their refusal of newer agents, highlighting a requirement to improve patient education. Targeting communities through awareness campaigns was identified as a viable solution.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) 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 ≥ 75 years) 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: < 65 years (n = 152), 65-74 years (n = 104), and ≥ 75 years (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 < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64-74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) 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 < 75 years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.