Low-density Lipoprotein Cholesterol Management Research Articles

Assessing LDL Cholesterol Management and Statin Use in Diabetic Patients: Disparities and Outcomes in a Vietnamese Tertiary Hospital Setting

Assessing LDL Cholesterol Management and Statin Use in Diabetic Patients: Disparities and Outcomes in a Vietnamese Tertiary Hospital Setting

Pragmatic Trial of Messaging to Providers About Treatment of Hyperlipidemia (PROMPT-LIPID): A Randomized Clinical Trial.

Lipid-lowering therapy (LLT) is underutilized for very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID (PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia) sought to determine whether electronic health record (EHR) alerts improve 90-day LLT intensification in patients with very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID was a pragmatic trial in which cardiovascular and internal medicine clinicians within Yale New Haven Health (New Haven, CT) were cluster-randomized to receive an EHR alert with individualized LLT recommendations or no alert for outpatients with very high-risk atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol), ≥70 mg/dL. The primary outcome was 90-day LLT intensification (change to high-intensity statin and addition of ezetimibe or PCSK9i [proprotein subtilisin/kexin type 9 inhibitors]). Secondary outcomes included LDL-C level, proportion of patients with LDL-C of <70 or < 55 mg/dL, rate of major adverse cardiovascular events, ED visit incidence, and 6-month mortality. Results were analyzed using logistic and linear regression clustered at the provider level. The no-alert group included 47 clinicians and 1370 patients (median age, 71 years; 50.1% female, median LDL-C, 93 mg/dL); the alert group included 49 clinicians and 1130 patients (median age, 72 years; 47% female, median LDL-C 91, mg/dL). The primary outcome was observed in 14.1% of patients in the alert group as compared with 10.4% in the no-alert group. There were no differences in any secondary outcomes at 6 months. Among 542 patients whose clinicians (n=46) did not dismiss the EHR alert recommendations, LLT intensification was significantly greater (21.2% versus 10.4%, odds ratio, 2.33 [95% CI, 1.48-3.66]). With a real-time, targeted, individualized EHR alert as compared with usual care, the proportion of patients with atherosclerotic cardiovascular disease with LLT intensification was numerically higher but not statistically significant. Among clinicians who did not dismiss the alert, there was a > 2-fold increase in LLT intensification. EHR alerts, coupled with strategies to reduce clinician dismissal, may help address persistent gaps in LDL-C management. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04394715, https://www.clinicaltrials.gov/ct2/show/study/NCT04394715.

Managing hypercholesterolaemia.

Hypercholesterolaemia is one of the most common conditions treated by clinicians in Australia. Low-density lipoprotein cholesterol (LDL-C) plays a causal role in the development and progression of atherosclerosis and cardiovascular disease. Every 1 mmol/L reduction in LDL-C concentration is associated with a 21 to 25% reduction in the relative risk of prospective atherosclerotic cardiovascular events, and emerging evidence suggests this benefit increases over time. Absolute cardiovascular risk assessment identifies patients likely to derive the most benefit from lowering LDL-C concentration, and helps determine the intensity of their treatment regimens and targets. Optimal management of LDL-C may require combination treatment with multiple classes of drugs.

Evolocumab-Based LDL-C Management in High and Very High Cardiovascular Risk Patients in German Clinical Practice: The HEYMANS Study.

Low-density lipoprotein cholesterol (LDL-C) is among the most important modifiable risk factors for cardiovascular disease. In very high-risk patients, the European Society of Cardiology/European Atherosclerosis Society guidelines recommend attaining LDL-C < 55mg/dL. In the German cohort of the observational HEYMANS study, we aimed to describe the clinical characteristics and LDL-C control among patients initiating evolocumab. Data was collected between 09/2016 and 05/2021 for ≤ 6months before (retrospectively) and ≤ 30months after evolocumab initiation (prospectively). Patient characteristics, lipid-lowering therapy (LLT), lipid values, evolocumab use, and safety were collected. Of 380 enrolled patients, 93% received evolocumab in secondary prevention and 69% had a history of statin intolerance. At study baseline, 49% did not receive any statins and LDL-C was very high (145mg/dL). Use of evolocumab decreased LDL-C by a median of 53% within 3months and remained stable thereafter, despite mainly unchanged background LLT. Overall, 59% attained an LDL-C level < 55mg/dL (69% with, 49% without LLT). Persistence to evolocumab was 90.6% in months 1-12 and 93.5% in months 13-30. Adverse drug reactions were reported in 8% of patients. Data from the German HEYMANS cohort corroborate previous reports on evolocumab effectiveness and safety in clinical practice. Evolocumab initiation was associated with a rapid and sustained LDL-C reduction. Persistence with evolocumab was high. Our finding that patients receiving an evolocumab/LLT combination are more likely to attain the LDL-C goal than those receiving evolocumab alone corroborates previous data showing the importance of using highly intensive therapy. Graphical abstract available for this article. ClinicalTrials.gov Identifier NCT02770131 (registration date 27 April 2016).

LOGAN-CV: A Prospective Study of a Multifaceted Intervention Targeting United States Clinicians to Improve Guideline-Based Management of Lipid-Lowering Therapy.

The 2018 American Heart Association (AHA)/American College of Cardiology (ACC)/Multisociety blood cholesterol guidelines recommend clinicians consider adding non-statin therapy for patients with very high-risk (VHR) atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) ≥ 70mg/dl while receiving maximally tolerated statins. However, according to a recent study, only 17.1% of patients with established ASCVD received appropriate lipid-lowering therapy (LLT) intensification. Here, we describe the design of a prospective, 12-month study (LOGAN-CV) evaluating a multifaceted site-level intervention to enhance clinicians' adherence to guidelines to improve LDL-C levels for patients with VHR ASCVD. Clinicians from up to ten research sites are eligible if they care for adult patients with ASCVD. Interventions include educational modules, a cloud-based performance platform providing clinicians a tailored summary of their LDL-C management performance, newsletters, periodic peer-to-peer calls, and pre- and post-intervention surveys evaluating knowledge, attitudes, and beliefs around LDL-C management, with additional interventions for clinicians demonstrating a lower readiness to make treatment decisions based on guideline recommendations. Patients with VHR ASCVD, defined as having recent myocardial infarction and LDL-C ≥ 70mg/dl despite statin treatment, will be included in the study. Patient data will be collected from electronic medical records from baseline (clinician enrollment) through the 12-month intervention. The study started in October 2022, with anticipated completion in March 2024. The change in proportion of patients with LDL-C < 70mg/dl achieved at any time during the 12-month intervention (primary); LLT intensification, changes in guideline-aligned LDL-C testing and LLT titration over 12months, and change in overall clinicians' knowledge, attitudes, and beliefsare key outcomes of interest. The LOGAN-CV study addresses a critical unmet need in LDL-C control in patients with VHR ASCVD and evaluates the effect of a multifaceted intervention targeting clinicians to improve their adherence to guidelines and consequently improve clinical outcomes for patients.

Therapeutic gaps in low-density lipoprotein cholesterol management have narrowed over time but remain wide: a wide study of 40,141 acute coronary syndrome patients from 2016 to 2021

Abstract Background There are significant therapeutic gaps in ‘real-word’ low-density lipoprotein cholesterol (LDL-C) management in very-high risk patients. Understanding these gaps is important for developing strategies to bridge these gaps. Purpose We aimed to evaluate trends and identify therapeutic gaps in LDL-C management in very-high risk patients. Methods We retrospectively analyzed consecutive patients admitted with a diagnosis of acute coronary syndrome (ACS) to 16 public hospitals in between 2016 and 2021. Baseline and 12-month lipid-lowering therapy (LLT) including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and LDL-C levels were recorded. We evaluated trends-over-time in percentage achievement of guideline Class I recommendations including (i) in-hospital initiation of high-intensity LLT; (ii) lipid-profile at follow-up post discharge; (iii) achieve at least 50% reduction in LDL-C from baseline with a goal of (iv) LDL-C &amp;lt;1.4 mmol/L. Results Of 40,141 ACS patients (mean age 71, male 66.5%), 61.2% were statin-naïve on admission. Baseline average LDL-C was 2.35 mmol/L (IQR 1.74 to 3.13 mmol/L). LLT prescription on discharge increased over time from 63.8% in 2016 to 96.2% in 2021. The use of high-intensity statins on discharge also increased over time from 24.7% to 53.7% but still suboptimal. The use of high-intensity statins increased significantly at 12-months (29.4% in 2016 and 59% in 2021) compared to on discharge (44.1% vs. 40.9% overall, p&amp;lt;0.001). The use of combination LLT was very low (1.3%-3.8%). Up to 22% of patients did not have repeated lipid profile after discharge. Of patients who had follow-up lipid profile, the median LDL-C was 1.74 mmol/L with a median LDL-C reduction of 29%. Only 27.5% reached the LDL-C goal of &amp;lt;1.4 mmol/L and 22.5% achieved at least 50% of LDL-C reduction. LDL-C reduction improved over time from 25.8% in 2016 to 31% in 2021, proportion of patients who reached LDL-C goal of &amp;lt;1.4 mmol/L improved over time from 20.8% in 2016 to 28.7% in 2021, and proportion of patients who achieved at least 50% of LDL-C reduction improved over time from 18.5% in 2016 to 24.6% in 2021, respectively. Conclusion Despite an increasing trend in the use of high-intensity statins and combination LLT over time, most patients did not reach guideline-recommended LDL-C target. Early up-titration of statin and addition of non-statin LLT may be required in the majority of patients.

Guideline-directed low-density lipoprotein cholesterol management following acute ischemic stroke: findings from Clalit health services

Abstract Background Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated (2019) guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets after ischemic stroke are limited. Methods Data from a single national health care service on patients hospitalized with acute ischemic stroke between Jan. 2020 and Feb. 2022. Included were 3027 patients surviving ≥1-year post-stroke, with documented LDL-C levels and lipid-lowering medications at 2 timepoints (&amp;lt;3 months and during 6-12 months post-discharge). Participants were classified according to preexisting stroke and/or coronary artery disease (CAD). Results LDL-C levels &amp;lt;70 mg/dL and &amp;lt;55 mg/dL were attained by 42.3% and 22.9% of patients early post-hospitalization, and in 49.5% and 27.1% during 6-12 months post-hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in those with preexisting cardiovascular disease. The use of combination lipid-lowering therapy (ezetimibe and/or PCSK9 inhibitor plus statin) increased between the 2 timepoints: from 2% to 3.2% in those without prior stroke and/or CAD, and from 5.4% to 7% in those with prior stroke and/or CAD. Conclusions Despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies 6-12 months following hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Insufficient long-term LDL-cholesterol management in patients with familial hypercholesterolemia 5 years after an acute coronary syndrome

Abstract Background Long-term control of cardiovascular risk factors after an acute coronary syndrome (ACS) is a cornerstone in preventing cardiovascular event recurrence. In patients with familial hypercholesterolemia (FH) and ACS, long-term management of LDL-cholesterol has been poorly studied. Purpose To investigate the extent of LDL-c and other cardiovascular risk factor management 5 years after ACS in patients with and without FH. Methods We collected data from 3,201 patients with an ACS from a Swiss multicenter cohort study and with 5-years follow-up data. At hospital admission for ACS, clinical FH was defined based on personal and familial history of premature cardiovascular disease as well as LDL-c levels, using the Dutch Lipid Clinic and the Simon Broome definitions. At the 5-years follow-up visit after ACS, we assessed LDL-c levels, lipid-lowering drugs, and control of cardiovascular risk factors comparing patients with FH and without FH. Results At the time of ACS, mean age of the 3,201 patients was 61.6 years old (SD 12.2), 643 (20.1%) were female, and 740 (23.1%) were diagnosed with clinical FH. At 5-years follow-up post-ACS, mean age was 56.6 years for FH patients and 69.6 years for patients without FH. 5 years after ACS, 15.4% and 33.5% patients with FH had an LDL-cholesterol ≤ 1.4 mmol/l, respectively ≤ 1.8 mmol/l, compared with 21.0% and 44.3% of those without FH (p=0.01, respectively &amp;lt;0.001) (see Figure and Table). Use of statins was similar between groups, but patients with FH were more frequently using high-dose statins compared to patients without FH (51.0% vs 42.9%, p&amp;lt;0.001). Use of lipid-lowering therapy in general such as statins, ezetimibe, fibrates, or niacin was more frequent in patients with FH than in those without FH (91.0% vs 87.0%, p=0.01). Beside LDL-c management, 5-year control of other cardiovascular risk factors tended to be superior in FH patients as compared to patients without FH: 78.5% vs 69.0% p&amp;lt;0.001 for systolic blood pressure (BP) &amp;lt; 140 mmHg; 46.2% vs 38.9% p=0.4 for reaching HbA1c &amp;lt; 7% in patients with diabetes; 46.9% vs 42.7% p=0.27 for smoking cessation, and 28.2% vs 21.0% p=0.1 for reduction of alcohol consumption &amp;lt;14 units/week . Conclusion Five years after an ACS, patients with FH had less optimal control of LDL-c levels despite being younger and more frequently using high dose statins compared to patients without FH. Combination of lipid-lowering therapy needs to be studied for optimal long-term management of patients with ACS and FH.Figure:CVRF 5 years post-ACS FH/non-FHTable:CVRF 5 years post-ACS FH/non-FH

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.

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis.

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.

Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Quality control to improve LDL-cholesterol management in patients with acute coronary syndromes based on the ACS EuroPath IV project.

We performed quality control of lipid-lowering therapy (LLT) in patients with acute coronary syndrome (ACS), with a view to proposing corrective actions. Using a Define Measure Analysis Improve Control (DMAIC) approach applied to data from the ACS EuroPath IV survey, we measured attainment of two quality indicators (QIs) related to lipid-lowering treatment: (i) prescription of high-intensity statins (or equipotent treatment) before discharge, and (ii) proportion with LDL-cholesterol <55 mg/dL (1.4 mmol/L) during follow-up. A total of 530 European cardiologists responded and provided data for up to 5 patients from their centre, for acute and follow-up phases. Corrective measures are proposed to increase the rate of attainment of both QIs. Attainment of the first QI was measured in 929 acute-phase patients, 99% had LLT prescribed at discharge and 75% of patients fulfilled the first QI. Attainment of the second QI was assessed in 1721 patients with follow-up. The second QI was reached in 31% of patients. The DMAIC approach yielded 10 potential changes in prescription, 3 for the first and 7 for the second QI. The overall strategy is 'Fire to Target', i.e. early intensification of the LLT using statins, ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type-9 inhibitors, and is presented as an algorithm for routine application. Quality control for LLT, based on the ACS EuroPath IV survey, detected 10 potential changes in prescription that could enhance attainment of 2 QIs. Whether the Fire to Target strategy will be adopted and effective needs to be assessed in further steps of the EuroPath Quality programme.

Update About the Management of Low-Density Lipoprotein Cholesterol and Hypertriglyceridemia in Lower Extremity Peripheral Artery Disease Patients: Consensus of the French Society of Vascular Medicine and the French Society for Vascular and Endovascular Surgery

A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required. A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement". Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose±ezetimibe and who have an LDLc ≥0.70g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150mg/dL and ≤500mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram. This update will help clinicians to improve LEAD patient management.

Differences in lipid and blood pressure measurements between individuals with type 1 diabetes and the general population: a cross-sectional study

ObjectivesCardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of CVD. However, age-specific...

Misperceptions and management of LDL-cholesterol in secondary prevention of patients with familial hypercholesterolemia in cardiology practice: Real-life evidence from the EPHESUS registry

Misperceptions and management of LDL-cholesterol in secondary prevention of patients with familial hypercholesterolemia in cardiology practice: Real-life evidence from the EPHESUS registry

Clinical Characteristics of Homozygous Familial Hypercholesterolemia in Japan: A Survey Using a National Database

BackgroundThe studies evaluating patients’ characteristics and lipid-lowering therapy for patients with homozygous familial hypercholesterolemia (HoFH) are scarce. ObjectivesThis study aims to evaluate the characteristics of and treatments for patients with HoFH. MethodsThis study included 201 patients who were diagnosed with definite or probable HoFH from the National Database of the Japanese Ministry of Health, Labour, and Welfare. ResultsThe patients’ median age at diagnosis was 27 years and exhibited a bimodal distribution. Approximately 70% of patients had coronary artery disease. Regarding genetic backgrounds, mutations in the low-density lipoprotein (LDL) receptor (LDLR) were identified in most of the patients, followed by proprotein convertase subtilisin/kexin type 9 (PCSK9) and double heterozygotes of LDLR. High-intensity statins were introduced to 74% of the patients, lipoprotein apheresis was performed in 21%, and PCSK9 inhibitors were administered to 50%. The mean of LDL cholesterol before and after treatment were 10.1 mmol/L and 3.9 mmol/L, respectively. Patients with coronary artery disease had significantly decreased LDL cholesterol. A quarter of the patients (n = 49, 24%) exhibited valvular diseases, particularly aortic valvular disease (n = 34, 61%). ConclusionsThe national epidemiological study of patients with HoFH showed patient’s clinical and genetic characteristics and LDL-lowering therapy in Japan. There was considerable diversity in the severity of phenotypes, including LDL cholesterol levels, among patients with HoFH. In Japan, the management of LDL cholesterol in HoFH is still inadequate despite the availability of intensive lipid-lowering therapies.

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.

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3months and 6 to 12months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55mg/100ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Optimal lipid-lowering therapy in patients who were functionally deferred percutaneous coronary intervention

Deferral of percutaneous coronary intervention (PCI) for functionally insignificant stenosis, defined as fractional flow reserve (FFR) > 0.80, is associated with favorable long-term prognoses. The lower-the-better strategy for low-density lipoprotein cholesterol (LDL-C) management is an established non-angioplasty therapy to improve the clinical outcomes of patients undergoing PCI. We examined the optimal LDL-C management in cases of intermediate coronary stenosis with deferred PCI on the basis of FFR values. This observational study included 273 consecutive patients with a single target vessel and deferred PCI with an FFR > 0.80. Patients with an FFR of 0.81–0.85 (n = 93) and those with FFR > 0.85 (n = 180) were classified into the lower (< 100 mg/dL) and higher (≥ 100 mg/dL) LDL-C groups. The endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, non-fatal myocardial infarction, ischemic stroke, heart failure hospitalization, and unplanned revascularization. Patients with an FFR of 0.81–0.85 had a significantly higher MACCE rate than those with an FFR > 0.85 (log-rank, p = 0.003). In patients with an FFR of 0.81–0.85, the lower LDL-C group showed a significantly lower MACCE rate than the higher LDL-C group (log-rank, p = 0.006). However, the event rate did not differ significantly between the two groups in patients with FFR > 0.85 (log-rank, p = 0.84). Uncontrolled LDL-C levels were associated with higher MACCE rates in cases with deferred PCI due to an FFR of 0.81–0.85. This high-risk population for adverse cardiovascular events should receive strict LDL-C-lowering therapy.

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.