Proprotein convertase subtilisin/kexin type 9 inhibitors in peripheral artery disease: A review of efficacy, safety, and outcomes.

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.

Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism.

In this study, 39 strains of lactic acid bacteria were screened from several fermented foods. Based on the evaluation of functional and prebiotic properties, Lactiplantibacillus plantarum SDJ09 was selected as a promising candidate. It gave a 48.16% cholesterol reduction and 33.73% pancreatic lipase inhibition in cells; exhibited high resistance to acid, bile salts, and gastrointestinal fluid; and had strong antibacterial activity and high adhesion capabilities. More importantly, the lipid-lowering effect of L. plantarum SDJ09 was also investigated using 3T3-L1 mature adipocytes and HepG2 nonalcoholic fatty liver disease models. L. plantarum SDJ09 effectively decreased triglyceride accumulation by more than 50% in both cell models, in which the expression of PPARγ, C/EBPα, aP2, and LPL in 3T3-L1 cells was significantly downregulated by L. plantarum SDJ09. L. plantarum SDJ09 also improved lipid metabolism by downregulating the expression of HMGCR, SREBP-1c, ACC, and FAS and upregulating the expression of CYP7A1 in HepG2 nonalcoholic steatohepatitis cells. Therefore, L. plantarum SDJ09 has the potential to effectively decrease obesity and non-alcoholic fatty liver disease (NAFLD) by inhibiting lipid accumulation, providing a prospective probiotic agent for anti-obesity.

Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study.

Background: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis. Methods: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran's Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk. Results: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma. Conclusions: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.

Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). METHODS: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. RESULTS: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. CONCLUSIONS: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

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.

Apple cider vinegar for weight management in Lebanese adolescents and young adults with overweight and obesity: a randomised, double-blind, placebo-controlled study.

Background and aims: Obesity and overweight have become significant health concerns worldwide, leading to an increased interest in finding natural remedies for weight reduction. One such remedy that has gained popularity is apple cider vinegar (ACV). Objective: To investigate the effects of ACV consumption on weight, blood glucose, triglyceride and cholesterol levels in a sample of the Lebanese population. Materials and methods: 120 overweight and obese individuals were recruited. Participants were randomly assigned to either an intervention group receiving 5, 10 or 15 mL of ACV or a control group receiving a placebo (group 4) over a 12-week period. Measurements of anthropometric parameters, fasting blood glucose, triglyceride and cholesterol levels were taken at weeks 0, 4, 8 and 12. Results: Our findings showed that daily consumption of the three doses of ACV for a duration of between 4 and 12 weeks is associated with significant reductions in anthropometric variables (weight, body mass index, waist/hip circumferences and body fat ratio), blood glucose, triglyceride and cholesterol levels. No significant risk factors were observed during the 12 weeks of ACV intake. Conclusion: Consumption of ACV in people with overweight and obesity led to an improvement in the anthropometric and metabolic parameters. ACV could be a promising antiobesity supplement that does not produce any side effects.

Relationships between sodium, fats and carbohydrates on blood pressure, cholesterol and HbA1c: an umbrella review of systematic reviews.

Background: The relationship between nutrition and health is complex and the evidence to describe it broad and diffuse. This review brings together evidence for the effect of nutrients on cardiometabolic risk factors. Methods: An umbrella review identified systematic reviews of randomised controlled trials and meta-analyses estimating the effects of fats, carbohydrates and sodium on blood pressure, cholesterol and haemoglobin A1c (HbA1c). Medline, Embase, Cochrane Library and Science Citation Index were search through 26 May 2020, with supplementary searches of grey literature and websites. English language systematic reviews and meta-analyses were included that assessed the effect of sodium, carbohydrates or fat on blood pressure, cholesterol and HbA1c. Reviews were purposively selected using a sampling framework matrix. The quality of evidence was assessed with A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) checklist, evidence synthesised in a narrative review and causal pathways diagram. Results: Forty-three systematic reviews were included. Blood pressure was significantly associated with sodium, fibre and fat. Sodium, fats and carbohydrates were significantly associated with cholesterol. Monounsaturated fat, fibre and sugars were associated with HbA1c. Conclusion: Multiple relationships between nutrients and cardiometabolic risk factors were identified and summarised in an accessible way for public health researchers. The review identifies associations, inconsistencies and gaps in evidence linking nutrition to cardiometabolic health.

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 (≥ 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.

Association of lipid-lowering drugs with gut microbiota: A Mendelian randomization study.

BACKGROUND: The gut microbiota can be influenced by lipid metabolism. We aimed to evaluate the impact of lipid-lowering medications, such as proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors, Niemann-Pick C1-like protein (NPC1L1) inhibitors, and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors, on gut microbiota through drug target Mendelian randomization (MR) investigation. METHODS: We used genetic variants that were associated with low-density lipoprotein cholesterol (LDL-C) in genome-wide association studies and located within or near drug target genes as proxies for lipid-lowering drug exposure. In addition, expression trait loci in drug target genes were used as complementary genetic tools. We used effect estimates calculated using inverse variance weighted MR (IVW-MR) and summary data-based MR (SMR). Multiple sensitivity analyses were performed. RESULTS: Genetic proxies for lipid-lowering drugs broadly affected the abundance of gut microbiota. High expression of NPC1L1 was significantly associated with an increase in the genus Eggerthella (ß = 1.357, SE = 0.337, P = 5.615 × 10-5). An HMGCR-mediated increase in LDL-C was significantly associated with the order Pasteurellales (ß = 0.489, SE = 0.123, P = 6.955 × 10-5) and the genus Haemophilus (ß = 0.491, SE = 0.125, P = 8.379 × 10-5), whereas a PCSK9-mediated increase in LDL-C was associated with the genus Terrisporobacter (ß = 0.666, SE = 0.127, P = 1.649 × 10-5). No pleiotropy was detected. CONCLUSIONS: This drug target MR highlighted the potential interventional effects of lipid-lowering drugs on the gut microbiota and separately revealed the possible effects of different types of lipid-lowering drugs on specific gut microbiota.

Exploring the Perceptions and Behaviours of UK Prescribers Concerning Novel Lipid-Lowering Agent Prescriptions: A Qualitative Study.

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.

Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.

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.

The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias.

This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes. Innovative funding models, such as value-based pricing and outcome-based payment arrangements, have been recommended to make novel LLTs more accessible. Public health interventions, including community-based programs and telemedicine, can be utilized to reach underserved populations and improve medication adherence. Education and advocacy initiatives led by patient advocacy groups and healthcare providers play a crucial role in raising awareness and empowering patients. Despite the barriers to access, novel LLTs present a big opportunity to reduce the burden of ASCVD, emphasizing the need for collaborative efforts among policymakers, healthcare providers, industry stakeholders, and patient advocacy groups to address these barriers to improve access to LLTs globally.

Cholesterol Lowering in Older Adults: Should We Wait for Further Evidence?

PURPOSE OF REVIEW: Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75 years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75 years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies. RECENT FINDINGS: The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75 years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

Early administration of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain. METHODS: This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included. RESULTS: Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization. CONCLUSION: Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence.

Lipid-lowering effect and oral transport characteristics study of curculigoside.

Introduction: The incidence of metabolic disorders during pregnancy is increasing year by year, with diseases including hypertension and hyperlipidemia. Statins are the primary drugs for treating hyperlipidemia or atherosclerosis, yet some patients remain unresponsive to them, and pregnant women are prohibited from taking statins. Curculigoside is the major biologically active natural product present in Curculigo orchioides. Methods: In this study, A high-fat mice model was developed to study the lipid-lowering effect of curculigoside. Using intestinal Caco-2 cell monolayer, the curculigoside transport properties at two temperatures and possible transporters were systemically studied. Results: Curculigoside at concentrations used during the experiments have no toxic effect to Caco-2 cells. The curculigoside transfer from the apical to the basolateral side was strongly influenced by temperature. P-glycoprotein, breast cancer resistance protein, and efflux transporters are crucial components of the human intestinal cell line Caco-2. The curculigoside can significantly affect the contents of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in mice. Discussion: The transport properties and potential mechanism of curculigoside offer valuable insights for the design of development of hypolipidemic drugs like anti-atherosclerotic drugs and also be helpful to the further study of the pharmacological activity of curculigoside.

Real-world experience of long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia treated and not treating with lipoprotein apheresis.

BACKGROUND: Evinacumab is an inhibitor of angiopoietin-like 3 protein (ANGPTL3) that offers a new approach for correcting high low-density lipoprotein-cholesterol (LDL-C) and may reduce the need or frequency for lipoprotein apheresis (LA) in patients with homozygous familial hypercholesterolemia (HoFH). OBJECTIVE: We aimed to investigate the long-term efficacy and safety of evinacumab in patients with HoFH aged between 14 and 63 years on and off LA in real-world clinical practice. METHODS: Evinacumab was administrated intravenously (15 mg /kg Q4W) for the first 24 months in 7 patients with genetically confirmed HoFH, receiving best standard of lipid-lowering treatment and LA, followed by a subsequent compassionate extension period of approximately 12-month treatment with evinacumab without LA. Patient experience of evinacumab and health-related EuroQol (EQ-5D-3L) quality of life questionnaire were also assessed. RESULTS: Compared with baseline, evinacumab resulted in a sustained reduction in plasma LDL-C concentration of -43.4 % and -54.2 % at 30 and 36 months, respectively. All 7 HoFH patients achieved an LDL-C reduction >30 % with 3 patients having on-treatment LDL-C level < 2.5 mmol/L (96 mg/dL). Evinacumab was well-tolerated, with no major adverse reported or significant changes in liver enzyme concentrations. All FH patients agreed that evinacumab was acceptable and less physically demanding than LA. The mean utility score and EQ- visual analogue scale scores were 0.966 and 78.6, respectively, which are comparable to the Italian general population. CONCLUSIONS: Our findings suggest that evinacumab is a safe and effective treatment for high LDL-cholesterol that is acceptable to HoFH patients receiving and not receiving LA.

Medication Adherence and Treatment Satisfaction With Lipid-Lowering Drugs Among Patients With Diabetes and Dyslipidemia.

BACKGROUND: Poor adherence to lipid-lowering drugs in diabetic patients with dyslipidemia increases has been linked with an increased cardiovascular risk. A better understanding of the determinants of adherence to lipid-lowering drugs and treatment satisfaction among people with diabetes and dyslipidemia is crucial. OBJECTIVE: We aimed to assess the prevalence of adherence to lipid-lowering drugs, identify its determinant factors, and evaluate treatment satisfaction among users of lipid-lowering drugs who have diabetes and dyslipidemia. METHODS: We surveyed 398 adult patients with diabetes and dyslipidemia, using a validated medication adherence survey (Adherence to Refills and Medications Scale) and a validated treatment satisfaction survey (Treatment Satisfaction Questionnaire for Medication, TSQM). Sociodemographic and medical history data were collected through questionnaires. RESULTS: The prevalence of poor medication adherence was 36%. Factors associated with poor adherence included adverse reactions to medications, lack of medication availability, and lack of family support. Adherent patients reported lower low-density lipoprotein-cholesterol (LDL-C) and total cholesterol levels, higher treatment satisfaction, and a higher prevalence of cardiovascular disease and comorbidities. Having a family history of dyslipidemia was negatively associated with adherence, while the number of comorbidities positively influenced it. The scores of TSQM components such as effectiveness, global satisfaction, and convenience were significantly higher in people who were adherent or achieved the LDL-C target. CONCLUSION AND RELEVANCE: Our findings highlight the need for interventions targeting several factors impacting adherence to lipid-lowering drugs in patients with diabetes and dyslipidemia. Managing adverse effects, leveraging family support, and ensuring medication access represent crucial aspects of improving adherence and potentially mitigating cardiovascular risks in this high-risk population.

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

BACKGROUND: Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. METHODS: A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. RESULTS: Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.534-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. No associations were observed for the other medications. CONCLUSIONS: Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

Role and impact of a specialized cardiometabolic clinic in managing high-risk patients with type 2 diabetes and atherosclerotic cardiovascular disease.

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond.

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.