Low-density Lipoprotein Cholesterol Target Research Articles

Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg Using a 2-mL Autoinjector Device in Real-World Practice: The MARS Study.

Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration. Monthly application of 300 mg AlirRocumab (Praluent®) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks. Patients included had primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia and confirmed vascular disease and other risk factors or confirmed familial heterozygous hypercholesterolemia. Primary objectives were to assess the effectiveness of the 2-mL SYDNEY autoinjector measured by the lipid-lowering effect of alirocumab and to document therapy satisfaction, patient adherence, and persistence. Secondary objectives were to assess safety (adverse events) and tolerability. A total of 146 patients were analyzed: 110 (75.3%) patients were proprotein convertase subtilisin kexin type 9 inhibitor naïve and 36 (24.7%) were pre-treated with a proprotein convertase subtilisin kexin type 9 inhibitor. Patient mean age was 65.6 years with a preponderance of male gender (59.6%). At 12 weeks, the LDL-C value had decreased by a median of 59.5 mg/dL (1.5 mmol/L) in naïve patients (median relative decrease: -52.0%). In the pre-treated group, the LDL-C value remained mainly unchanged (median slight numerical relative increase: 1.6%). Treatment satisfaction was rated similarly in both groups with most patients being satisfied/very satisfied and rating the injection as effective, safe, and easy to handle. Twenty-three adverse events in 13 patients (8.0%) were documented. Three patients experienced one serious adverse event each; for five patients, an adverse drug reaction was observed, although none was serious. The occurrence of adverse events was similar in both groups. Alirocumab 300 mg administered with the 2-mL SYDNEY autoinjector was safe and effective in lowering LDL-C after 12 weeks in a routine clinical setting in Germany. The treatment schedule was perceived to be beneficial with excellent device acceptance and satisfaction, potentially increasing patient adherence. Clinicaltrials.gov: NCT05129241.

Current Status and Prospects of Regional Collaborative Pathways for Management of Acute Coronary Syndrome in Japan - A Nationwide Survey.

Comprehensive management of acute coronary syndrome (ACS) requires seamless treatment across institutions, including intensive care centers and local clinics. However, maintaining guideline-directed medical therapy remains challenging. One promising option to improve the situation may be the implementation of regional collaborative clinical pathways. This study evaluated the prevalence and functionality of such pathways for ACS in Japan. A nationwide survey was conducted through questionnaires and web searches, targeting all 47 prefectural managers of Japanese Circulation Association (JCA) branches. The study focused on pathways managed at the prefectural or regional levels, excluding inactive or institutional pathways. In all, 18 pathways were identified: 11 (23%) prefecture wide and 4 (9%) region wide. Most pathways included risk factor targets such as low-density lipoprotein cholesterol (LDL-C), HbA1c, and blood pressure, but only 8 pathways set an LDL-C target of <70 mg/dL. Pathways updated between 2022 and 2024 and incorporating LDL-C management protocols were considered functional. In all, 45 JCA branches viewed future ACS pathways established by the government or academic societies as potentially useful resources. Regional collaborative clinical pathways for ACS patients in Japan show variable implementation across prefectures, with approximately one-third of prefectures having established pathways. Future efforts should prioritize the establishment of comprehensive, sustainable, and standardized pathways to optimize ACS management and improve patient outcomes nationwide.

Bempedoic Acid: A Review in Cardiovascular Risk Reduction in Statin-Intolerant Patients.

Oral bempedoic acid (NEXLETOL® in the USA; Nilemdo® in the EU) and the fixed dose combination (FDC) of bempedoic acid/ezetimibe (NEXLIZET® in the USA; Nustendi® in the EU) are approved to reduce cardiovascular (CV) risk in statin-intolerant patients who are at high risk for, or have, CV disease. A first-in-class therapy, bempedoic acid inhibits the adenosine triphosphate-citrate lyase enzyme in the cholesterol biosynthesis pathway. In the multinational phase III CLEAR Outcomes trial in statin-intolerant patients, once-daily bempedoic acid 180mg significantly reduced the risk of the primary endpoint (a four-component major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) compared with placebo. Bempedoic acid was generally well tolerated and, unlike statins, was associated with a low incidence of musculoskeletal adverse events (AEs). In conclusion, bempedoic acid as a monotherapy or adjunctive to other lipid-lowering therapies expands the treatment options available for the pharmacological reduction of CV risk in statin-intolerant patients, supporting achievement of low-density lipoprotein cholesterol (LDL-C) targets required for CV risk reduction.

Inadequate awareness and attention to non-HDL cholesterol: undertreatment of high-risk patients in cardiology practice in Turkey.

The relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) is well-established. Recently, non-high-density lipoprotein cholesterol (non-HDL-C) has been validated as a superior predictor of ASCVD, especially in individuals with mild to moderate hypertriglyceridemia. The EPHESUS study evaluated real-life hypercholesterolemia management and awareness of non-HDL-C in cardiology outpatient practices. Data from 1868 patients with ASCVD or high-risk primary prevention were analyzed to assess cholesterol goal attainment, statin adherence, and physician perceptions. This analysis focused on awareness of non-HDL-C as an ASCVD predictor, adherence to lipid-lowering therapy, and clinicians' perceptions. Associations between patient demographics, clinical characteristics, and statin adherence were examined. Among patients, 20.2% achieved non-HDL-C and 16.5% achieved LDL-C goals. In primary prevention, 18.1% reached non-HDL-C and 10.6% reached LDL-C goals, while in secondary prevention, 20.8% and 18.0% met these goals. High-intensity statin therapy was observed in 21.2% of patients, with 30.3% and 24.3% achieving non-HDL-C and LDL-C targets, respectively. Statin use was lower in women than men (54.0% vs 66.9%, P < 0.001). Women less frequently achieved non-HDL-C and LDL-C goals in both prevention groups. Non-HDL-C goal attainment remains suboptimal in both primary and secondary prevention of hypercholesterolemia, particularly in women who had lower statin use and goal achievement. These findings highlight the need for improved awareness, education, and treatment strategies to reduce residual cardiovascular risk and improve outcomes.

Lipid Management in US Commercial and Medicare Enrollees with Atherosclerotic Cardiovascular Disease: Treatment Patterns and Low-Density Lipoprotein Cholesterol Control.

Lipid-lowering therapy (LLT) is the cornerstone for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet many patients exhibit low adherence to therapy and fail to achieve low-density lipoprotein cholesterol (LDL-C) goals. This retrospective cohort study used 2 nationally representative administrative closed claims databases (PharMetrics® Plus and Medicare Fee-for-Service [FFS] Research Identifiable Files) to identify commercial (C) and Medicare (M) enrollees with ASCVD between 2014-2019. Patients were stratified by exposure to statin therapy, ezetimibe and proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9i mAb) regimens. Outcomes included LLT adherence (proportion of days covered [PDC] ≥0.8), persistence, and discontinuation at 12 months. For patients with LDL-C test results, percent achieving LDL-C <70 mg/dL during follow-up was evaluated. We identified 4.6 million patients with ASCVD (C: 945,704, M: 3,659,011), majority with ischemic or coronary heart disease. Of those, C:66.4% and M:71.4% were on at least 1 LLT, including C:69.8% and M: 71.4% on statin therapy, C: 2.7% and M:1.7%% on ezetimibe, and C:0.2% and M:0.04% on a PCSK9i mAb. By month 12, medication discontinuation was: C:30.4% and M:34.1% for statin therapy, C:35.5% and M:46.1% for ezetimibe and C:41.5%, M:55.8% for PCSK9i mAb. Approximately half of treated patients remained adherent at 12 months. Of patients with LDL-C data available (n=381,160), <20% achieved an LDL-C <70 mg/dL. In conclusion, medication discontinuation and low adherence to statin therapy, ezetimibe, and PCSK9i mAb were seen in both populations. Increased efforts are needed to ensure persistence and adherence to LLT in patients with ASCVD to attain LDL-C targets.

Therapeutic Inertia in Dyslipidemia Management for Secondary Cardiovascular Prevention: Results from the Italian ITACARE-P Network.

Background/Objectives: This study assessed the proportion of secondary cardiovascular prevention patients who achieved low-density lipoprotein (LDL) cholesterol targets as per the 2019 ESC/EAS Dyslipidemia Guidelines. We also evaluated whether lipid-lowering therapies (LLTs) were adjusted in patients not meeting targets and analyzed the likelihood of these modifications achieving recommended levels. Methods: A multicenter, cross-sectional observational study retrospectively reviewed medical records of 1909 outpatients in 9 Italian cardiac rehabilitation/secondary prevention clinics from January 2023 to June 2024. Inclusion criteria included prior atherosclerotic cardiovascular disease (ASCVD) and recent LDL-cholesterol levels. Data included demographics, ASCVD presentation, lipid profiles, and LLTs. Patients at very high risk had LDL targets of ≤55 mg/dL, or ≤40 mg/dL for recurrent events within 2 years. Clinicians' approaches to LLT modification in patients not at target were recorded, with LLT efficacy estimated based on percentage distance from LDL-cholesterol targets. Results: Of the 1909 patients, 41.3% met the LDL-cholesterol target. Predictors of achieving targets included male gender, cardiac rehabilitation, recent acute coronary syndrome, diabetes, and triple therapy (statin + ezetimibe + PCSK9 inhibitors). Conversely, a target of ≤40 mg/dL, lack of therapy, and monotherapy were negative predictors. Among 1074 patients not at target, LLT modifications were proposed for 48.6%. Predictors of LLT modification included recent ASCVD events, cardiac rehabilitation, and greater percentage distance from the LDL target, while advanced age and an LDL target of ≤40 mg/dL were negative predictors. However, only 42.3% of modified therapies were predicted to be effective in reaching LDL targets. Conclusions: Despite 2019 ESC/EAS guidelines, a significant proportion of high-risk patients did not achieve LDL targets, and proposed LLT modifications were often insufficient. More intensive LLT regimens are needed to improve outcomes in this population.

Management of Children with Heterozygous Familial Hypercholesterolemia Worldwide: A Meta-Analysis

Abstract Background Heterozygous familial hypercholesterolemia (HeFH) is one of the most frequent monogenic disorders in the world, leading to premature atherosclerotic cardiovascular diseases (ASCVD). The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of low-density lipoprotein cholesterol (LDL-C) goal in children with HeFH. Methods The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (&amp;lt;3.5 mmol/L/130 mg/dL). Results A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. 17 reported the efficacy and safety of LLT therapy compared to control, while the remaining assessed LLT through pre- and post-treatment. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p&amp;lt;0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by statins in monotherapy, PCSK9 inhibitors, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p&amp;lt;0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p&amp;lt;0.001) and failed to reach the goal treatment (&amp;lt;3.5 mmol/L) by 12.6% (95%CI, 12.4–12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between &amp;gt;10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal &amp;lt;3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p&amp;gt;0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. Conclusions Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.

Escalating Lipid Therapy After Achieving LDL-C

Guidelines recommend target levels of low-density lipoprotein cholesterol (LDL-C) and intensive lipid-lowering therapy (LLT) in high-risk patients. However, the value of escalating LLT when the LDL-C targets are achieved with moderate-intensity statins is unknown. We aimed to evaluate the benefits of LLT escalation in this population. In this retrospective propensity score-matched study, we screened data from two university hospitals between 2006 and 2021. Of the 54,069 patients with atherosclerotic cardiovascular disease (ASCVD), 3,205 who achieved LDL-C levels <70 mg/dL with moderate-intensity statins were included. After 1:3 matching, 1,315 patients (339 with LLT escalation and 976 without) were ultimately examined. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE)1 (cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke) and all-cause death. During a median follow-up of 5.7 years, the MACCE1 rate was not significantly lower in the escalation group than in the non-escalation group (9.8 and 14.3/1,000 person-years, respectively; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.43-1.09; p=0.11). Kaplan-Meier curves showed similar results (log-rank p=0.11). The risk of all-cause death did not differ between the groups. MACCE2 rate, which additionally includes coronary/peripheral revascularization, was lower in the escalation group (24.5 and 35.4/1,000 person-years, respectively; HR, 0.70; 95% CI, 0.52-0.94; p=0.017). LLT escalation did not significantly lower hard cardiovascular outcomes and all-cause death in patients with ASCVD achieving LDL-C levels <70 mg/dL with moderate-intensity statins. However, it had benefit in reducing revascularization rates in this population.

Association of LDL-cholesterol with prognosis in patients admitted for acutely decompensated heart failure.

The association of low-density lipoprotein cholesterol (LDL-C) levels and prognosis in patients with heart failure (HF) remains uncertain. This study aimed to evaluate the prognostic significance of LDL-C in patients admitted for acutely decompensated HF and establish a safety cut-off value in this population. This retrospective, observational study included 167 consecutive patients admitted for acute HF. LDL-C levels were measured on hospital admission, and patients were categorized according to their estimated cardiovascular (CV) risk. The primary endpoint was all-cause mortality at 1-year, while secondary endpoints included HF hospitalizations, major thrombotic events, and net clinical benefit. During the follow-up period, 14.4% of patients died. Higher LDL-C levels were independently associated with improved survival, with a 4-fold increase in survival probability for each 1mg/dL increase in serum LDL-C. The minimum LDL-C value not associated with increased mortality risk was 88mg/dL. Patients with LDL-C below this cut-off had a significantly higher risk of mortality and a tendency for higher HF hospitalization risk. The net clinical benefit endpoint was also influenced by LDL-C levels, with LDL-C below 88mg/dL associated with an increased risk of events. In patients admitted for acutely decompensated HF, higher LDL-C levels were associated with reduced risk of mortality. An LDL-C value below 88m/dL was associated with increased mortality, suggesting the need for a more liberal LDL-C target in this specific patient population. These findings highlight the importance of considering LDL-C levels in the management and risk assessment of patients with HF.

Systematic Review on Efficacy, Effectiveness, and Safety of Pitavastatin in Dyslipidemia in Asia.

Objectives: Dyslipidemia, a significant risk factor for cardiovascular disease (CVD), is marked by abnormal lipid levels, such as the elevated lowering of low-density lipoprotein cholesterol (LDL-C). Statins are the first-line treatment for LDL-C reduction. Pitavastatin (PIT) has shown potential in lowering LDL-C and improving high-density lipoprotein cholesterol (HDL-C). This review assesses pitavastatin's efficacy, effectiveness, and safety in dyslipidemia management in Asia. Methods: A systematic review was conducted using PubMed, Cochrane, and Embase databases up to November 2024, adhering to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies (12 RCTs and 5 non-RCTs) were analyzed, focusing on LDL-C reduction, safety profiles, and adverse events. The quality of the studies was assessed using checklists to ensure the selection of the best studies and to limit bias. Results: Pitavastatin doses (1-4 mg) reduced LDL-C by 28-47%, comparable to atorvastatin, rosuvastatin, and simvastatin. The 2 mg dose matched atorvastatin's 10 mg dose in efficacy for both short-term (35-42%) and long-term (28-36%) use. LDL-C target achievement rates were 75-95%. Adverse events, including mild myalgia and elevated liver enzymes, were rare, and discontinuation rates were low. Conclusions: Pitavastatin is an effective and safe alternative to traditional statins for dyslipidemia management in Asia. Further research on long-term outcomes and high-risk groups is warranted.

Assessment of dyslipidemia management in Turkey using a Delphi panel

This study evaluated the management of dyslipidemia in Turkey with the goal of understanding current diagnosis and treatment patterns, as well as identifying unmet needs in achieving effective low-density lipoprotein cholesterol (LDL-C) targets. Using a Delphi panel consisting of nine expert cardiologists, the study reveals key gaps in dyslipidemia management, particularly in the underutilization of combination therapies, such as statins and PCSK9 inhibitors, which are crucial for achieving LDL-C targets in high-risk patients. The findings indicate that while many patients with very high cardiovascular risk are diagnosed, a significant proportion do not receive optimal treatment to reach LDL-C levels recommended by European guidelines. Addressing these gaps could lead to more effective management of dyslipidemia and reduce the burden of cardiovascular disease in Turkey. The study’s insights provide critical recommendations for clinicians and policymakers to improve clinical practice and health outcomes through more aggressive lipid-lowering strategies.

The Integrated Multidisciplinary Pathway for Large-Scale Management of Dyslipidemia in High-Risk Patients (ENNA) Project: Rationale and Project Design.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality globally, significantly influenced by modifiable risk factors, particularly hypercholesterolemia. Despite the availability of effective lipid-reducing drugs, achieving the low-density lipoprotein cholesterol (LDL-C) target levels remains a significant challenge in clinical practice, contributing to persistently high rates of cardiovascular events. The intEgrated multidiscipliNary pathway for large-scale maNagement of dyslipidemiA in high-risk patients (ENNA) Project was designed to address the alarming rates of suboptimal lipid management in patients at great and very great risk in the province of Enna, Sicily. This program aims to optimize LDL-C control through an integrated care model that fosters collaboration among pharmacists, general practitioners, and cardiologists, ultimately promoting a patient-centered approach to therapy. The patients who are eligible are identified using data-driven methods through prescription claims, laboratory results, and hospital discharge data, facilitated by local pharmacies. General practitioners play a crucial role as the primary care providers for initiating or optimizing lipid-reducing therapy, whereas cardiologists are involved in managing more complex cases requiring specialized intervention. The primary objective of the ENNA Project is to increase the percentage of patients at great risk in whom LDL-C targets are achieved, improving overall lipid management and therapeutic adherence.

Safety and efficacy of moderate-intensity statin with ezetimibe in elderly patients with atherosclerotic cardiovascular disease.

High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins. To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy. In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5mg with ezetimibe 10mg) or high-intensity statin monotherapy (rosuvastatin 20mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70mg/dL) within 6 months. The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p=0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels. Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.

Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.

Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy?

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As atherosclerosis is marked by chronic arterial inflammation, the innate and adaptive immune systems play vital roles in its progression, either exacerbating or alleviating disease development. This intricate interplay positions the immune system as a compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none have yet reached widespread clinical adoption. Safety concerns, particularly the suppression of host immune defenses, remain a significant barrier to the clinical application of anti-inflammatory therapies. Recent decades have revealed the significant role of adaptive immune responses to plaque-associated autoantigens in atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related autoantigens can slow disease progression while preserving systemic immune function. In this context, numerous experimental studies have advanced the understanding of vaccine development by exploring diverse targeting pathways. Key strategies include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies and active immunization targeting low-density lipoprotein cholesterol (LDL-C) and apolipoproteins, such as apolipoprotein B100 (ApoB100) and apolipoprotein CIII (ApoCIII). Other approaches involve vaccine formulations aimed at proteins that regulate lipoprotein metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and angiopoietin-like protein 3 (ANGPTL3). Furthermore, the literature highlights the potential for developing non-lipid-related vaccines, with key targets including heat shock proteins (HSPs), interleukins (ILs), angiotensin III (Ang III), and a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe and effective clinical therapies presents substantial challenges. This review provides a critical evaluation of current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms of action, and discusses key challenges that need to be overcome to enable clinical translation.

Effectiveness of Lower Range of High-intensity Statin Therapy in Lowering LDL-C among STEMI Patients

Background: Lipid-lowering is an important intervention to reduce cardiovascular morbidity and mortality after ST-Elevation myocardial infarction. This study aimed to assess the proportion of such patients achieving guideline-directed therapeutic low-density lipoprotein cholesterol targets while on lower-range high-intensity statin treatment.Methods: This is a cross-sectional study conducted in Shahid Gangalal National Heart Centre, a tertiary cardiac center in Kathmandu, Nepal, from November 2021 to July 2022 among admitted acute ST-Elevation myocardial infarction patients who were prescribed a lower range of high-intensity statin therapy, Atorvastatin 40mg and Rosuvastatin 20 mg. Clinical characteristics were collected, including lipid parameters at baseline during admission and three months after the treatment. The proportion attaining the guideline-recommended levels was calculated and compared between each statin group. Results: A total of 240 patients were included in this study. The target low-density lipoprotein cholesterol level of less than 1.4mmol/L was noted only in 16.3% and the target reduction by ≥50% from baseline only in 7.1%. Just 3.3 % achieved a target of &lt;1.4 mmol/L and ≥50% reduction from baseline. However, 40.8% of the participants in our study met the 2012 European Society of Cardiology guidelines’ target achievement of less than 1.8 mmol/L. Conclusions: The overall proportion of patients attaining recommended low-density lipoprotein cholesterol levels after recent ST-Elevation myocardial infarction was low when patients were prescribed with a lower range of high-intensity statin, reflecting the need for rigorous follow up including monitoring of lipid levels and intensification of statin dose and type as recommended by international guidelines.Keywords: Low-Density Lipoprotein Cholesterol; secondary prevention; statin; statin intensity; ST-Elevation myocardial infarction.

Evaluation of Lipid Profile and Statin Therapy in Patients with Atrial Fibrillation: Real-Life Data from a Tertiary Hospital

Objectives: Dyslipidemia is a modifiable risk factor of atrial fibrillation (AF). However, the majority of patients either do not receive low-density lipoprotein cholesterol (LDL-C) lowering treatment or do not meet their LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) goal. We aimed to search whether patients with AF are being treated for dyslipidemia and/or are at target LDL-C and non-HDL-C levels if treated. Methods: This cross-sectional analysis includes 725 AF patients and was performed between 20 May 2023 and 25 November 2023, in cardiology outpatient clinics of a tertiary hospital. The demographic and clinical features of the patients were recorded. Systemic coronary risk estimation-2 (SCORE2) and old person version algorithms were used for cardiovascular disease (CVD) risk estimation. Primary prevention (PP) group involved patients with low-to-moderate, high and very high CVD risk without established atherosclerotic cardiovascular disease (ASCVD) and secondary prevention (SP) group was consisted of patients with established ASCVD. Results: The mean age of the participants was 71.98± 9.01 and 54.5% (n=368) of patients were females. 207 (30.7%) of patients were paroxysmal AF, and 468 (69.3%) were permanent AF. Prevalence of dyslipidemia and hypertriglyceridemia were 364 (53.9%) and 248 (36.7%) respectively. 9 (1.3%) and 152 (22.5%) of patients were on fibrate and statin treatment respectively. Mean LDL-C and non-HDL-C were 107.81±35.97 and 135.42±41.19 and their target attainment rates were 62 (9.2%) and 107 (15.9%), respectively. Conclusion: Control of dyslipidemia in patients with atrial fibrillation was severely poor and the most common cause was physician negligence.

Impact of obesity on low density lipoprotein plasmatic levels 6 weeks after an acute coronary syndrome.

Cardiovascular disease is the leading cause of death. One of the main factors is obesity, which is on the rise. LDL levels below 0.55 g/L are recommended after ACS. To date, there are no specific recommendations for obese subjects. The primary objective was to assess the impact of obesity on LDL-c target attainment 6 weeks after initiation of statin therapy in subjects admitted for ACS. The secondary objectives were to assess the evolution of cholesterol levels and to characterize lipid-lowering treatments. The single-center observational study took place at Montpellier University Hospital and included patients admitted to the ICU for ACS not treated with statins (T0). Biological tests were performed at 6 weeks. At 3 months, a telephone call was made by two pharmacists to collect the results of their biological work-up and any therapeutic modifications. The results were analyzed on 286 patients. A total of 39.5% were overweight and 22.7% obese. After hospitalization, 95.4% were prescribed statins. At 6 weeks, LDL cholesterol averaged 1.58 mmol/L, lower in subjects with a BMI greater than 30 kg/m2 (1.32 mmol/L). On average, 49.46% of subjects reached the LDL cholesterol target, with obese subjects achieving a higher rate of 64.9%. There was no significant difference in the prescription of lipid-lowering treatments between the two groups. Despite high-intensity statin prescription, the target was achieved by 67.6% of obese subjects and 44.8% of subjects with a BMI of less than 30 kg/m2. This shows that post-SCA management needs to be reinforced for the general population.

Evaluation of lipoprotein(a) — a novel cardiovascular risk factor in patients with atherosclerotic cardiovascular diseases receiving PCSK9-targeted therapy in Russian real-world practice

Aim. To evaluate the effect of PCSK9-targeted therapy on lipoprotein(a) (Lp(a)) levels in patients with atherosclerotic cardiovascular diseases who have not achieved the target low-density lipoprotein cholesterol (LDL-C) level (statins at maximum tolerated doses and/or ezetimibe).Material and methods. The study involved 3 Moscow medical facilities of the state healthcare system. The study included 50 people who received inclisiran therapy, 30 people — PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29). This analysis presents the results of Lp(a) level changes over 12-month inclisiran therapy. Lp(a) was determined by turbidimetry. Elevated Lp(a) level was defined as ≥50 mg/dL (125 nmol/L).Results. Normal Lp(a) levels were determined in 16 subjects (34,8%), moderate — in 9 subjects (19,6%), high — in 21 subjects (45,7%), and extremely high (&gt;180 mg/dL) — in 8 subjects (17,4%). Inclisiran therapy was associated with a significant (p&lt;0,001) decrease in both LDL-C and Lp(a) levels by 52% and 54,7%, respectively. During therapy, normal Lp(a) levels remained within baseline values. In almost half of the cases with moderate Lp(a) values, its concentration decreased to normal values, and in cases with elevated Lp(a), its level decreased in 9 out of 10 patients. The proportion of patients in the group with Lp(a) levels &lt;30 mg/dl increased from 35% to 41%. No patient had extreme values by the end of the study.Conclusion. Lp(a) assessment may be appropriate with ongoing PSCK9-targeted therapy. Diagnosis of hyper-Lp(a) is important for early intensive combination lipid-lowering therapy and modification of risk factors in order to reduce the risk of cardiovascular diseases.

Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials.

Cardiovascular disease is a leading cause of mortality, especially in individuals with type 2 diabetes mellitus and dyslipidemia. Despite adequate statin therapy, some patients fail to achieve the target low-density lipoprotein-cholesterol levels. Trials have compared doubling the statin dose with the addition of ezetimibe. A systematic literature search was performed using various databases. Forest plots were constructed for pooled analysis with statistical significance set at P < 0.05. Seven trials were included. Monotherapy showed no significant difference compared with dual therapy for low-density lipoprotein-cholesterol levels [mean difference (MD): -5.03; P = 0.37], high-density lipoprotein-cholesterol levels (MD: 0.01; P = 0.95), total cholesterol (MD: -2.38; P = 0.66), and triglycerides (MD: 5.37; P = 0.67) at follow-up compared to baseline. Monotherapy significantly reduced serious clinical adverse events (risk ratio: 0.21; P = 0.04), with no difference in treatment-related adverse effects, discontinuation due to treatment-related or overall adverse events.