Low-density Lipoprotein Cholesterol Reduction Research Articles

Low-density Lipoprotein Cholesterol Reduction Therapies for Secondary Prevention in Patients with Stroke: A Network Meta-analysis.

Patients with previous strokes are at a higher risk of stroke recurrence. Current guidelines recommend a range of low-density lipoprotein cholesterol (LDL-C)-lowering treatments to reduce the risk of recurrent stroke. However, the optimal agent for decreasing LDL-C to lower the risk of recurrent stroke remains unclear. This study aimed to assess the relative effects of various LDL-C -lowering agents for secondary stroke prevention. Several databases were searched from inception up to 2022. Only randomized controlled trials that compared different LDL-C-lowering agents in adult patients with previous strokes were included. The primary endpoint was a recurrent stroke. The surface under the cumulative ranking curve (SUCRA) was also applied to estimate the overall ranking probability of the treatment agents for each outcome. Overall, nine trials comprising 17,226 patients were included. Ezetimibe plus statins (RR: 0.56, 95% CrI: 0.35-0.87) and statins alone (RR: 0.90, 95% CrI: 0.81-1.00) reduced the risk of stroke recurrence. Ezetimibe plus statins was superior to statins alone in decreasing the incidence of recurrent stroke (RR: 0.62, 95% CrI: 0.39-0.95). However, treatment with statins was related to an increased risk of hemorrhagic stroke compared to placebo (RR: 1.57, 95% CrI: 1.13-2.21). All agents were related to a decreased incidence of major adverse cardiovascular events. Treatment with ezetimibe plus statins was suggested as the most efficacious in decreasing the incidence of recurrent stroke. The analysis also revealed that statin monotherapy was related to an increased risk of hemorrhagic stroke.

Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study

Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder characterised by extremely high concentrations of LDL cholesterol, leading to early-onset atherosclerosis. Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that effectively lowers LDL cholesterol and is approved for adults with HoFH. We aimed to investigate the efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy. APH-19 is an open-label, single-arm, phase 3 trial performed at 12 study centres in Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. A 6-week run-in period was followed by a 24-week efficacy phase and an 80-week safety phase. Patients aged 5-17 years, on stable lipid-lowering therapy, with HoFH diagnosed using the criteria from the 2014 European Atherosclerosis Society Consensus Panel on HoFH were titrated to maximum tolerated doses of oral lomitapide, starting at 2 mg (patients aged 5-15 years) or 5 mg (patients aged 16-17 years). The primary endpoint was the percentage change from baseline to week 24 in LDL cholesterol, which was assessed in patients who had received at least one dose of lomitapide, and who had a baseline and at least one post-baseline measurement. The secondary outcomes were the percentage change from baseline at week 24 in total cholesterol, non-HDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04681170. Between Dec 20, 2020, and Oct 16, 2022, 43 patients were included and treated (24 [56%] were female and 19 [44%] were male, and median age was 10·7 years [7·0-14·0]). Mean change from baseline in LDL cholesterol at week 24 was -53·5% (95% CI -61·6 to -45·4, p<0·0001). Mean percentage reductions were observed at week 24 for non-HDL cholesterol (-53·9%, 95% CI -61·7 to -46·1, p<0·0001), total cholesterol (-50·0%, 95% CI -57·6 to -42·4, p<0·0001), VLDL cholesterol (-50·2%, -59·1 to -41·2, p<0·0001), apolipoprotein B (-52·4%, -60·3 to -44·5, p<0·0001), triglycerides was -49·9% (-58·8 to -41·0, p<0·0001), and lipoprotein(a) (-11·3%, -32·9 to 10·3 [in 21 patients with measurements in mg/dL]; -23·6%, -38·2 to -9·0 [in 22 patients with measurements in nmol/L]; p=0·0070 combined). Adverse events were mostly mild, and gastrointestinal and hepatic in nature. Adverse events of special interest were reported for five (12%) patients (gastrointestinal in two patients and hepatic in three). One serious treatment-emergent adverse event was reported (also classed as an adverse event of special interest): an increase in hepatic enzymes, resulting in two dose interruptions, two dose reductions, and a repeated dose escalation. Lomitapide provided a significant, clinically meaningful LDL cholesterol reduction and has the potential to be an efficient, LDL receptor-independent option for paediatric patients with HoFH. Amryt Pharmaceuticals.

Innovative drugs for LDL-cholesterol reduction: a new era in the field of dyslipidaemia

Over the past decade, the therapeutic landscape of cholesterol-lowering drugs has rapidly expanded to address the limitations of current therapies, the failure to achieve LDL-C targets, and the need to reduce cardiovascular residual risk. Actually, the innovative cholesterol-lowering drugs available can act on new metabolic pathways involved in LDL-C metabolism. These drugs include enzyme inhibitors, peptides, molecules capable of influencing protein synthesis or gene in the form of antisense oligonucleotides or short interfering RNA, gene therapy, and vaccines.

From clinical development to real-world outcomes with inclisiran.

Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process. To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events. Inclisiran has been evaluated in numerous trials, primarily the ORION 926, ORION 1027 and ORION 1128 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.

A Comparative Analysis of Low-Density Lipoprotein Cholesterol (LDL-C)-Lowering Activities of Bempedoic Acid, Inclisiran, and PCSK9 Inhibitors: A Systematic Review.

Newer drugs, such as bempedoic acid, inclisiran, alirocumab, and evolocumab have recently been introduced for dyslipidemia. This systematic review aims to perform a comparative analysis of these drugs' low-density lipoprotein cholesterol (LDL-C)-lowering activities. The PubMed database was utilized to search for randomized controlled trials. Articles were screened and selected based on specific inclusion and exclusion criteria. The primary outcome of this review is to compare the percentage reduction of LDL-C and apolipoprotein-B, along with the number of reported serious adverse events (SAEs) in trials specific to each drug. A total of 14 studies were included, four for bempedoic acid and alirocumab and three for evolocumab and inclisiran. The maximum percentage reduction in LDL-C and apolipoprotein-B from baseline to 12 weeks was observed with alirocumab, administered at 150 mg subcutaneously twice weekly for 12 weeks, achieving reductions of 72.4% and 57.9%, respectively. Lesser reductions were observed with bempedoic acid, administered at 180 mg once daily orally for 12 weeks. The highest number of SAEs were reported with bempedoic acid (216, 10%) and inclisiran (181, 11%; 175, 11%). This systematic review showed that alirocumab achieved the greatest reductions in LDL-C and apolipoprotein-B and a better safety profile. Newer LDL-C-lowering drugs show promise in improving lipid profiles, patient compliance, and safety. However, these findings are not conclusive, as other factors also influence treatment choice.

A Clinicians Guide to Recommending Common Cholesterol-Lowering Dietary Supplements.

The US dietary supplement (DS) market has expanded exponentially since 1994, with an estimated 50,000-80,000 individual products currently available. Many DS claim cholesterol or cardiovascular benefits. Overall, well-designed randomized controlled trials (RCTs) with DS are lacking, while studies with favorable results are commonly performed outside of the USA, resulting in inconsistent findings. The expansion of the DS market has limited the ability of the Food and Drug Administration to regulate and prevent substandard products. Eicosapentaenoic acid and docosahexaenoic acid are components of DS fish oil. Recent RCTs utilizing prescription fish oil have provided mixed findings and small but significant safety concerns. Hence, the role of DS fish oil is limited and no longer recommended by major cardiovascular guidelines. Concerns have also been observed from RCTs utilizing prescription niacin, resulting in a negligible role for DS niacin in lipid management. Red yeast rice has demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions in studies performed worldwide, including the USA. However, quality concerns and inconsistent study results have been reported on multiple occasions. Other common DS have produced modest reductions in LDL-C and may provide other cardiometabolic benefits, including garlic, phytosterols, psyllium, and berberine. Yet inconsistent study results and quality concerns continue to be reported for most. Nonetheless, there is a need for alternative therapies that can safely and effectively reduce cardiovascular risk. However, until DS routinely match label claims and are free of contaminants, the agents have a limited role in clinical practice.

Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody: Rationale and design of the randomized FITTER trial

Non-culprit coronary artery lesions are commonly present in patients presenting with an acute coronary syndrome (ACS). Additional stenting of non-culprit lesions in addition to the culprit lesion intends to prevent secondary events caused by these lesions. At the same time, multiple trials have demonstrated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in reducing plaque size and changing plaque composition of non-culprit lesions. Whether intensive low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibitor evolocumab improves non-culprit vessel hemodynamics, reduces the risk of plaque rupture of important non-culprit lesions, and might obviate the need for additional stenting has not been investigated. The “Functional Improvement of non‐infarcT related coronary artery stenosis by Extensive LDL‐C Reduction with a PCSK9 Antibody” (FITTER) trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial for patients presenting with ACS and multivessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) is performed in non-culprit vessels amenable for percutaneous coronary intervention (PCI). Coronary intervention in patients with hemodynamically important non-critical lesions (FFR: 0.67–0.85) is staged after baseline imaging using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). Eligible patients are randomized and treated for 12 weeks with either evolocumab or placebo, in addition to high-intensity statin therapy. Follow-up angiography with repeat FFR and IVUS-NIRS is scheduled at 12 weeks. Staged PCI is performed at the operator's discretion.The FITTER trial is the first study to evaluate the effect of maximal LDL-C reduction by the PCSK9 inhibitor evolocumab on invasively measured FFR, plaque size, and plaque composition in hemodynamically important non-culprit lesions, during a treatment period of just 12 weeks after an ACS. Currently, all patients have been included (August 2023) and data analysis is ongoing. Trial registration numberclinicaltrials.gov NCT04141579.

Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway.

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

The effects of alfalfa powder combined with health education on patients with dyslipidemia: A randomized controlled trial

BackgroundCardiovascular diseases (CVDs) remain the leading cause of global mortality, with dyslipidemia recognized as a significant risk factor. Dyslipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), is associated with an increased lifetime risk of CVD. Although alfalfa’s cholesterol-lowering effects have been demonstrated in animal models, clinical trial data supporting its efficacy in human dyslipidemia treatment are limited. MethodsA randomized controlled trial was conducted from September 20, 2021, to January 12, 2023, involving patients diagnosed with dyslipidemia. Approved by the China Ethics Committee of Registering Clinical Trials, the study included multiple sites in China. Eligible participants were adults aged 18 years or older, meeting criteria from the Chinese Guidelines for the Prevention and Treatment of Adult Blood Lipid Disorders. Participants were randomly assigned to either a health education-only group or a combined alfalfa powder supplementation and health education group for a three-month intervention period. ResultsA total of 160 eligible patients were enrolled and randomized into two groups: the Alfalfa group (n = 80) and the Education group (n = 80). The intervention resulted in significant improvements in key lipid parameters in the Alfalfa group, including reductions in TC, LDL-C, and Apo A1 levels. Although changes in HDL-C levels were not significantly different between the groups, the Alfalfa group exhibited a larger increase. Serum lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the combined intervention did not significantly alter the overall blood lipid metabolome but identified fifteen regulated differential metabolites, with the glycerophospholipid metabolism pathway significantly affecting lipid metabolism levels. ConclusionSupplementation with alfalfa powder combined with health education significantly reduced TC, LDL-C, and Apo A1 levels in patients with dyslipidemia. KEGG pathway analysis suggests an association between the glycerophospholipid metabolism pathway and dyslipidemia. Further research is warranted to validate these findings and explore the underlying mechanisms.

The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up.

Despite the availability of statins and lifestyle modifications, many patients with Dyslipidemia struggle to achieve optimal low-density lipoprotein cholesterol (LDL-C) control. PCSK9 inhibitors offer a promising new therapeutic option with superior LDL-C lowering efficacy compared to statins. However, data on their real-world use, particularly in Iran, is limited. This study aims to address this gap by investigating the one-year effects of evolocumab on lipid profiles and potential cardiovascular outcomes in Iranian patients with Familial Hypercholesterolemia (FH).This single-center, prospective study evaluated evolocumab effectiveness in lowering LDL-C in 50 Iranian adults with FH. Participants with a documented LDL-C > 190 mg/dL on existing cholesterol medications (excluding PCSK9 inhibitors) and a clinical FH diagnosis was included. After baseline assessments (medical history, demographics, lipid profile), evolocumab was administered subcutaneously every two weeks for one year. Follow-up assessments at year one measured changes in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The study enrolled 50 participants with an average age of 55 years old (range 35-80 years).Treatment with evolocumab led to significant improvements in lipid profiles at all follow-up points compared to baseline. On average, LDL-C levels decreased by 105.24 mg/dL, triglycerides decreased by 59.20 mg/dL, and HDL-C levels increased by a modest but significant 4.5 mg/dL after one year(p<0.001). Subgroup analysis revealed no statistically significant interactions between baseline demographics (age, sex, BMI) or lifestyle habits (smoking, alcohol) and changes in lipid levels(p>0.05). However, a significant interaction emerged between baseline lipid levels and their corresponding reductions, suggesting greater improvement in patients with higher baseline values(p<0.05). It is noteworthy that no new cardiovascular events were reported during the study period. This study demonstrates the effectiveness of evolocumab in improving lipid profiles in Iranian patients with FH. The observed reductions in LDL-C and triglycerides, along with a modest increase in HDL-C, suggest potential benefits for cardiovascular risk reduction. The absence of new cardiovascular events during the study is encouraging, but further research with larger and longer-term follow-up is needed to confirm these findings and assess the long-term safety and impact on quality of life.

Lipid-lowering therapy after acute coronary syndromes: a multinational European survey.

Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as early as possible to obtain >50% low-density-lipoprotein cholesterol (LDL-c) reduction and an LDL-c < 1.4 mmol/l. A multinational European survey study of ACS patients between 2021-2022 and acquired data on LLT and lipid levels on admission and during 1-year posthospitalization. We compared plasma lipid changes and adherence to post-ACS lipid targets across two in-hospital LLT groups: high-intensity statin (HIS) monotherapy (mono-HIS) and a combination of HIS and ezetimibe (combo-HIS). Of 286 patients, 268 (94%) received in-hospital HIS and were included in the final analysis. Patients (median age: 61.1 years) had a median baseline LDL-c of 3.3 mmol/l. Mono-HIS was the predominant in-hospital LLT (72.4%). In-hospital combo-HIS was administered in 27.6% of the cases. Patients from high-income countries (n = 141) were more likely to receive in-hospital combo-HIS than patients from middle-income countries [n = 127; 38.3% vs. 15.7% patients, P < 0.001). One-year post-ACS, 50 (26.5%) patients from the mono-HIS group received ezetimibe. The target of LDL-c ≤ 55 mg/dl was reached in 85 patients (31.7%), without significant difference between study groups [mono-HIS: 56 (28.9%) and combo-HIS: 29 (39.2%) patients, P = 0.10]. The target of >50% reduction was achieved more frequently among the combo-HIS group than in the mono-HIS group (50.0% vs. 29.9%, respectively, P = 0.002). LDL-c targets were achieved in less than half of the patients post-ACS, regardless of the LLT regimen. Combo-HIS was initiated in-hospital post-ACS in only 28% and was associated with greater LDL-c reduction compared to a staged approach of mono-HIS with up-titration at follow-up.

Lipid-lowering therapy in patients with coronary heart disease: an Italian real-life survey. Results from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES) in Italy.

In patients at high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) reduction of ≥50% from baseline and an LDL-C goal of <70 mg/dL (or <55 mg/dL in very high-risk patients) are recommended. Multiple registry and retrospective studies have shown that patients with high atherosclerotic cardiovascular risk often do not reach the targets defined by the European Society of Cardiology guidelines as a result of suboptimal management of LDL-C. Here, we report the data on lipid-lowering therapy and lipid targets from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES), an observational, prospective study designed to collect data on patients with ischemic heart disease treated at cardiac outpatient clinics across the Italian national territory. We included patients with known coronary heart disease (CHD) who underwent follow-up visits at various outpatient cardiology clinics. A total of 2532 patients were included (mean age: 67±17 years, 80% male). Among patients with available laboratory data (n=1712), 995 (58%) had LDL-C<70 mg/dL, 717 (42%) had LDL-C≥70 mg/dL, and 470 (27%) had LDL-C<55 mg/dL. Patients who more frequently achieved the recommended LDL-C levels were male, had diabetes, had a higher educational level, and performed intense physical activity. Statins were used in 2339 (92%) patients, high-intensity statins (e.g., rosuvastatin 20/40 mg or atorvastatin 40/80 mg) in 1547 patients (61% of the whole population and 66% of patients on statins), and ezetimibe in 891 patients (35%). Patients receiving high-intensity statins tended to be younger, not to have diabetes, and to have been included in a cardiac rehabilitation program. In a real-world sample of Italian patients with CHD, adherence to lipid-lowering therapy fell markedly short of optimal levels. Many patients did not achieve the LDL-C target of 70 mg/dL, and even fewer reached the LDL-C target of 55 mg/dL. Notably, patients with a lower educational level had a greater likelihood of being undertreated. Strategies aimed at improving preventive interventions for CHD and overcoming social disparities should be evaluated and optimized.

The Effect Of Weight Loss With Lifestyle Changes On LDL Cholesterol: Retrospective Cohort Study

Aim: This study aimed to investigate the rate of decrease in lipid levels with effective lifestyle changes (LC) and the minimum body weight loss necessary for effective lipid reduction in obese patients. Method: The study is a retrospective cohort study. The study included 71 patients who were followed up in the obesity clinic, who were diagnosed with hyperlipidemia but did not use any hyperlipidemia treatment. The patients' high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglyceride, body fat ratio and mass, body mass index (BMI), height and weight information were recorded at the first visit and the 6th month. In our study, patients were divided into two groups (based on the weight loss rates in the 6-month follow-up) those who lost less than 10% of their previous weight and those who lost 10% or more weight and their lipid parameters were compared. Results: LDL-C reduction rates of patients classified according to their weight loss rates were found to be statistically significantly (p=0.011) higher in those with 10% or more weight loss than (group 1=18.48%) in those with less than 10% weight loss (group 2=13.04%). Total cholesterol reduction rates were also significantly (p=0.015) higher in the 1st group than in the 2nd group. According to the findings of our study, at least 10% weight loss is required to decrease total cholesterol and LDL-C significantly. Conclusion: Implementation of primary and secondary prevention strategies to reduce the risk of cardiovascular disease is important in the context of primary care. To reach the targeted LDL-C values, the weight monitoring of obese patients should be considered, and the importance of losing at least 10% of weight as one of the first steps should be emphasized.

Rapid Lipid-Lowering Response in Two Cases of Autosomal Recessive Hypercholesterolemia

BackgroundAutosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the LDLRAP1 gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH). CaseWe present the cases of two siblings diagnosed with ARH caused by LDLRAP1 gene c.617-14C>A splicing homozygous variant. Over a five-year treatment period, the older sibling experienced an 81% reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75% reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis. ConclusionOur findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C>A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.

Impact of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 Probiotic Supplementation on the Gut Microbiome of Hypercholesterolemia Patients: A Randomized Controlled Trial.

Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

Characteristics of Patients With Atherosclerotic Cardiovascular Disease in Belgium and Current Treatment Patterns for the Management of Elevated LDL-C Levels.

Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined. Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal. Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice.

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials

Background and aimsStatins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons. MethodsWe conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people <18 years with HeFH. Comprehensive bibliographic searches were conducted in December 2022, and a Medline update in January 2024. NMA models accounted for drug class, statin type and dosage. ResultsThirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I2 = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI −11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo. ConclusionsStatins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by excessive hepatic fat accumulation without alcohol intake. It can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and liver failure. This study aims to evaluate the efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in treating NAFLD. A systematic review and meta-analysis was conducted including studies published from January 2018 to June 2023. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Inclusion criteria comprised randomized controlled trials and cohort studies involving human subjects or animal models with NAFLD. Data were extracted and analyzed to assess the impact of omega-3 PUFAs on liver fat, hepatic enzymes, and serum lipid profiles using RevMan 5.4. A total of 15 studies met the inclusion criteria. Omega-3 supplementation significantly decreased alanine aminotransferase (ALT) (mean difference = -2.12, 95% confidence interval (CI) = -3.36, -0.87) and aspartate aminotransferase (AST) (mean difference = -1.50, 95% CI = -2.59, -0.42). Gamma-glutamyl transferase levels showed a trend toward reduction (mean difference = -0.82, 95% CI = -1.66, 0.02). Serum lipid profiles improved significantly with reductions in triglycerides, low-density lipoprotein, and total cholesterol along with significant reductions in AST, ALT, and alkaline phosphatase in animal models. Omega-3 PUFAs appear to offer beneficial effects on liver enzymes, serum lipid profiles, and anthropometric indices in NAFLD patients. While their impact on liver fat content remains uncertain, omega-3 supplementation could serve as a valuable adjunct treatment for enhancing metabolic profiles and liver function in NAFLD patients.

Evolocumab (Repatha)

It is recommended that Repatha be reimbursed by public drug plans for the reduction of elevated low-density lipoprotein cholesterol (LDL-C) in adult patients with primary hyperlipidemia (atherosclerotic cardiovascular disease [ASCVD]) if certain conditions are met. Repatha should only be covered to treat patients with a recent acute coronary syndrome (ACS) event, defined as those who have been hospitalized for a heart attack or unstable angina in the past 52 weeks. Additionally, these are patients with an LDL-C level between 1.8 mmol/L and 2.2 mmol/L (inclusive) or a non–high-density lipoprotein cholesterol (non–HDL-C) level between 2.6 mmol/L and 2.9 mmol/L (inclusive) or an apolipoprotein B (ApoB) level between 0.7 g/L and 0.8 g/L (inclusive), despite receiving the highest dose of statin that can be tolerated and ezetimibe. Alternatively, these are patients with an LDL-C level greater than 2.2 mmol/L, a non–HDL-C greater than 2.9 mmol/L, or an ApoB greater than 0.8 g/L, despite receiving the highest dose of statin that can be tolerated, with or without ezetimibe. Repatha should only be reimbursed if prescribed by a cardiologist or internal medicine specialist with expertise in the post-ACS setting and if the cost of Repatha is reduced. Repatha should not be reimbursed for use in combination with other PCSK9 inhibitors.