INTRODUCTION: Achieving low-density lipoprotein cholesterol (LDL-C) levels is key to preventing atherosclerotic cardiovascular events. However, many high-risk cardiovascular patients still experience poor LDL-C goal attainment and receive suboptimal lipid-lowering therapy (LLT) prescriptions. Herein, we evaluated LLT prescription patterns, LDL-C goal attainment and cardiovascular mortality among this population group in Singapore. METHODS: This prospective observational cohort study included 555 patients with ischaemic heart disease (IHD) admitted to the hospital in 2020. The LLT prescriptions, corresponding LDL-C levels and cardiovascular outcomes were assessed over a 24-month period. RESULTS: Most participants were male (82.3%), with 48.5% identified as Chinese. High-intensity statin prescriptions increased from 45.4% at hospital admission to 87.1% at discharge and remained stable at approximately 80% at 6, 12, and 24 months post-discharge. Combination LLT prescriptions increased from 12.3% at discharge to 33.8% by 24 months. Ezetimibe was the most commonly prescribed second-line LLT (40.8%), followed by inclisiran (1.09%) and anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapies (0.87%). Over 24 months, LDL-C goal attainment rates were 22.1% for LDL-C < 1.4 mmol/L and 47.2% for LDL-C < 1.8 mmol/L. Multivariable Cox proportional hazards regression indicated that achieving LDL-C < 1.8 mmol/L goal was associated with a reduction in all-cause mortality at 24 months (hazard ratio 0.53, 95% confidence interval 0.30-0.94, P = 0.030). CONCLUSION Treatment gaps in lipid management persist in 80% of the study population, indicating that statin monotherapy alone is insufficient to achieve LDL-C goals. Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative.
Humans ; Male ; Cholesterol, LDL/blood* ; Female ; Myocardial Ischemia/drug therapy* ; Middle Aged ; Prospective Studies ; Aged ; Singapore/epidemiology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Ezetimibe/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome

Based on the similarity of chemical constituents between Panax notoginseng flowers and rhizomes, this study investigated their lipid-lowering effects and impacts on the intestinal flora of rats. The main components of P. notoginseng flowers and rhizomes were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) to compare their chemical similarities. A hyperlipidemia rat model was induced using a high-fat diet. After successful modeling, the rats were divided into the blank control group, blank administration group(0.090 g·kg~(-1)), model group, low-(0.045 g·kg~(-1)), medium-(0.090 g·kg~(-1)), high-dose(0.180 g·kg~(-1)) P. notoginseng flower group, P. notoginseng rhizome group(0.270 g·kg~(-1)), and simvastatin group(0.900 mg·kg~(-1)). After modeling, the rats were given intragastric administration for 3 weeks, once daily, while their body weight was recorded regularly. Before the last administration, fresh feces were collected for analysis of changes in intestinal flora using 16S rDNA high-throughput sequencing technology. One hour after the last administration, the rats were anesthetized with 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Serum biochemical indexes were detected using an automatic biochemical analyzer. Organs(heart, liver, spleen, lung, and kidney) were harvested, and organ index were calculated. Liver tissue pathology was assessed through HE staining and oil red O staining. The results indicated that there were 33 identical chemical constituents in P. notoginseng flowers and rhizomes, accounting for 75.00% of the total constituents. After treatment, high-dose P. notoginseng flower group and P. notoginseng rhizome group exhibited similar effects on body weight, serum biochemical indexes, and liver histopathological conditions. Compared with model control group, the abundance of Firmicutes and Actinobacteria increased in high-dose P. notoginseng flower and rhizome groups, while the abundance of Bacteroidetes and Thermodesulfobacteria decreased. Cluster analysis showed no significant difference between the two groups. Both P. notoginseng flowers and rhizomes possess similar chemical components and lipid-lowering effects, and they can regulate the intestinal flora imbalance caused by hyperlipidemia, indicating their potential for use in hyperlipidemia treatment.
Animals ; Hyperlipidemias/microbiology* ; Panax notoginseng/chemistry* ; Rats ; Rhizome/chemistry* ; Male ; Flowers/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/administration & dosage* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Liver/drug effects*

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVE: The aim of this study is to re-evaluate the systematic reviews and meta-analyses on statins for the treatment of erectile dysfunction (ED) and construct an umbrella review, thereby providing robust evidence-based for the clinical application of statins in ED treatment. METHODS: A comprehensive computerized search was conducted across CNKI, Wanfang Database, VIP, WOS, Embase, PubMed, and Cochrane Library databases from their inception to September 12, 2024, for all systematic reviews and meta-analyses addressing statin interventions in ED. The methodological quality, reporting quality, and evidence quality of the included studies were assessed and summarized using PRISMA 2020, AMSTAR 2, and GRADE systems. RESULTS: Four systematic reviews and meta-analyses were included. According to the AMSTAR 2 evaluation, one paper was rated as low quality, while the remaining three were classified as very low quality. PRISMA 2020 evaluation results indicated that the average score of the four included studies was 29, with all being of medium quality but exhibiting partial deficiencies. The proportion of fully consistent items across the four studies ranged from 52.38% to 80.95%. GRADE system tool evaluation revealed 11 outcome indicators, of which only one was rated as intermediate evidence. The remainders were categorized as low or very low evidence, with no high-quality evidence identified. CONCLUSION Statins demonstrate efficacy in treating ED. However, the current quality of relevant systematic reviews is suboptimal, with notable deficiencies in methodological, reporting, and evidential quality. Further high-quality studies are warranted to provide more reliable evidence-based medical guidance for clinical practice.
Humans ; Erectile Dysfunction/drug therapy* ; Male ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Meta-Analysis as Topic ; Systematic Reviews as Topic

Objectives: Bioequivalence studies provide evidence that generic drugs can produce the same blood levels as the innovator, suggesting similar efficacy and safety and indicating interchangeability without the need to titrate dosing. This study aimed to compare the rate and extent of absorption of two simvastatin 20 mg tablets of Pascual Laboratories, Inc. with two Zocor 20 mg tablets of Merck Sharp & Dohme (I.A.) Corp. in healthy Filipinos. The study also monitored the safety and tolerability of the medications, under the same conditions. Proof of bioequivalence is required by FDA Philippines to establish the interchangeability of generic products and their innovators. Methods: Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatin tablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study, with a washout period of one week. Pharmacokinetic blood sampling was done up to 24 h post-dose. Simvastatin was measured using Liquid Chromatography-Tandem Mass Spectrometry with a validated method. The geometric mean ratios for maximum plasma concentration (Cmax) and area under the plasma-concentration-time curve from time zero to the last observed concentration at time 24 h (AUC0-24) were used for bioequivalence. Results: All 24 participants, 12 males and 12 females, completed the study. Mean age was 24.21 years, mean weight was 58.81 kg, and mean BMI was 23.16 kg/m2. The ratios of Cmax and AUC0-24 were 102.17% (90% CI: 89.19-117.03), and 101.29% (90% CI: 86.87-118.10), respectively, and were both within the bioequivalence limits of 80% to 125%. No adverse event was reported and both formulations were well-tolerated. Conclusions Simvastatin 20 mg tablet of Pascual Laboratories, Inc. and the innovator Zocor 20 mg tablet are bioequivalent. Single two-tablet doses of both products are safe and well tolerated.
Simvastatin ; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.
Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Atorvastatin/adverse effects* ; Simvastatin/adverse effects* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Drug-Related Side Effects and Adverse Reactions/drug therapy*

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.
Male ; Humans ; Middle Aged ; Autoantibodies ; Myositis/diagnosis* ; Autoimmune Diseases ; Muscle, Skeletal/pathology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Necrosis/pathology* ; Muscular Diseases/drug therapy*

INTRODUCTION: Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use. METHODS: A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE. RESULTS: We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046). CONCLUSION Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.
Humans ; Male ; Aged ; Female ; Coronary Artery Disease ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Myocardial Perfusion Imaging/methods* ; Calcium ; Stroke Volume ; Brain Ischemia ; Risk Factors ; Ventricular Function, Left ; Stroke ; Prognosis

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.
Child ; Infant, Newborn ; Female ; Humans ; Cholesterol, LDL/therapeutic use* ; Liver Transplantation ; Homozygous Familial Hypercholesterolemia ; Retrospective Studies ; Hyperlipoproteinemia Type II/surgery* ; Lipids ; Hypolipidemic Agents/therapeutic use*