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 analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."
Biomarkers ; Cholesterol ; Drugs, Chinese Herbal ; Female ; Humans ; Hypercholesterolemia/drug therapy* ; Menopause

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.
Aged ; Antibodies, Monoclonal, Humanized ; Anticholesteremic Agents/therapeutic use* ; Cardiovascular Diseases/drug therapy* ; China ; Double-Blind Method ; Ezetimibe/therapeutic use* ; Humans ; Hypercholesterolemia ; Hyperlipidemias ; Male ; Middle Aged ; Proprotein Convertase 9 ; Risk Factors ; Treatment Outcome

The ultimate objective of dyslipidemia management is to prevent and treat atherosclerotic cardiovascular diseases. It is important to combine lifestyle modification together with medication. To determine whether to start drug therapy, comprehensive consideration should be given to both the risk status for atherosclerotic cardiovascular disease and low density lipoprotein cholesterol levels. Drug treatment can be initiated according to whether the patients have coronary artery disease, ischemic cerebral infarction, peripheral artery disease, atherosclerotic artery diseases (abdominal aortic aneurysm, carotid artery stenosis), or diabetes, as well as the number of atherosclerotic risk factors (smoking, hypertension, low high density lipoprotein cholesterol level, family history of premature coronary artery disease, and age). Statin is the first-choice drug for the treatment of hypercholesterolemia. The first goal for drug therapy is to lower the low density lipoprotein cholesterol and the secondary goal is to lower the non-high density lipoprotein cholesterol level. Secondary causes of dyslipidemia should be considered and corrected before starting any medication. These recommendations are based on the new treatment guideline 2015 of Korean Society of Lipidology and Atherosclereosis and Korean Medical Association.
Aortic Aneurysm ; Arteries ; Cardiovascular Diseases ; Carotid Arteries ; Cerebral Infarction ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Coronary Artery Disease ; Drug Therapy ; Dyslipidemias* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Hypertension ; Life Style ; Lipoproteins ; Peripheral Arterial Disease ; Risk Factors

The American College of Cardiology and the American Heart Association (ACC/AHA) 2013 joint guidelines for the treatment of hypercholesterolemia expand the indications for statin therapy. This study was performed to estimate the numbers of diabetic patients indicated for statin therapy according to the Third Adult Treatment Panel (ATP-III) of the National Cholesterol Education Program guidelines and the new ACC/AHA guidelines in Korea. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012. Patients with diabetes over 30 yr of age were analyzed by the two guidelines. Of the total 1,975 diabetic patients, only 377 (19.1%) were receiving drugs for dyslipidemia. Among 1,598 patients who had not taken any medications for dyslipidemia, 65.6% would be indicated for statin therapy according to the ATP-III guidelines. When we apply the new guidelines, 94.3% would be eligible for statin therapy. Among the total diabetic patients, the new guidelines, compared with the ATP-III guidelines, increase the number eligible for statin therapy from 53.1% to 76.2%. The new guidelines would increase the indication for statin therapy for most diabetic patients. At present, many diabetic patients do not receive appropriate statin therapy. Therefore efforts should be made to develop the Korean guidelines and to ensure that more diabetic patients receive appropriate statin therapy.
Adult ; Aged ; Animals ; Cardiology/*standards ; Causality ; Comorbidity ; Diabetes Mellitus/drug therapy/*epidemiology ; Female ; Guideline Adherence/utilization ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypercholesterolemia/*epidemiology/*prevention & control ; Male ; Middle Aged ; *Practice Guidelines as Topic ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; United States/epidemiology

BACKGROUND/AIMS: Many parasites induce changes in the lipid profiles of the host. Cholesterol increases the virulence of Entamoeba histolytica in animal models and in vitro culture. This study aimed to determine, in patients with an amebic liver abscess, the correlation between cholesterol and other features, such as the size and number of abscesses, standard hematological and serum chemistry profiles, liver tests, and duration of hospital stay. METHODS: A total of 108 patients with an amebic liver abscess and 140 clinically healthy volunteers were investigated. Cholesterol and triglycerides were measured in the sera. The data from medical observations and laboratory tests were obtained from the clinical records. RESULTS: A total of 93% of patients with an amebic liver abscess showed hypocholesterolemia not related to any of the studied parameters. Liver function tests correlated with the size of the abscess. The most severe cases of amebic liver disease or death were found in patients whose cholesterol levels continued to decrease despite receiving antiamebic treatment and hospital care. CONCLUSIONS: Our results show that the hypocholesterolemia observed in patients with an amebic liver abscess is not related to any of the clinical and laboratory features analyzed. This is the first study relating hypocholesterolemia to severity of hepatic amebiasis.
Amebicides/therapeutic use ; Cholesterol/metabolism ; *Entamoeba histolytica ; Female ; Humans ; Hypercholesterolemia/blood/*parasitology ; Length of Stay ; Liver Abscess, Amebic/blood/*complications/drug therapy ; Male ; Middle Aged ; Treatment Outcome

Atherosclerosis ; prevention & control ; Cholesterol, LDL ; blood ; Humans ; Hypercholesterolemia ; drug therapy ; United States

Atherosclerosis ; blood ; prevention & control ; Cardiovascular Diseases ; blood ; drug therapy ; prevention & control ; Cholesterol ; blood ; Humans ; Hypercholesterolemia ; drug therapy ; Practice Guidelines as Topic

OBJECTIVES: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. METHODS: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. RESULTS: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for beta-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. CONCLUSIONS: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends.
Adrenergic beta-Antagonists/therapeutic use ; Age Factors ; Aged ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases/complications/drug therapy/*epidemiology ; Diabetes Complications ; Diabetes Mellitus/diagnosis ; Female ; Humans ; Hypercholesterolemia/complications/diagnosis ; Hypertension/complications/diagnosis ; Male ; Middle Aged ; Percutaneous Coronary Intervention/*statistics & numerical data/trends ; Prevalence ; Registries/statistics & numerical data ; Risk Factors ; Smoking ; Time Factors

Lipid-lowering and antioxidant activities of a hydroalcoholic extract of Cyperus scariosus Linn. root (HCS) were evaluated in guinea pigs fed with a high cholesterol diet. Serum lipid profile (total cholesterol, triglycerides, LDL-C, VLDL-C, and HDL-C), atherogenic indices and serum enzymes (ALT, AST, ALP, LDH, and CK-MB) were performed in each group at 0 days and at the end of 60 days. Histological study of liver and kidney was done in groups 1, 2, 5, 6 and 7. The total phenolic and flavonoid content in HCS and its antioxidant activity were evaluated by the DPPH assay. Both doses of HCS decreased serum lipid profile and atherogenic indices (P < 0.05). HCS has lipid lowering, immunosuppressive and antioxidant properties, and mays have value in atherosclerosis prevention. The higher dose of HCS also reduced serum AST, ALP, and LDH levels and rosuvastatin increased AST and ALP levels (P < 0.05). Histology of the liver showed decreased lipid accumulation and improvement in hepatocytes in HCS-treated animals. The antioxidant activity of HCS may be responsible for its lipid lowering and cytoprotective action. HCS had significant lipid lowering and antioxidant activity, which; may be due to the phenolic compounds. HCS may be a safe and cost effective alternative to current statin therapy for patients with dyslipidaemia.
Animals ; Cyperus ; Female ; Guinea Pigs ; Hypercholesterolemia ; drug therapy ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Kidney ; pathology ; Liver ; pathology ; Male ; Mice ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; chemistry