The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia

The aim of this study was to assess the strength of hemostatic effects of ezetimibe, administered alone or in combination with simvastatin, in patients with isolated hypercholesterolemia. One hundred and four patients with isolated primary hypercholesterolemia were randomized to one of four treatment groups, simultaneously treated for 90 days with ezetimibe (10 mg daily), simvastatin (40 mg daily), ezetimibe (10 mg daily) plus simvastatin (40 mg daily), or placebo. Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of randomization and after 30 and 90 days of therapy. Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe, only simvastatin reduced plasma levels/activity of fibrinogen, factor VII, factor X, von Willebrand factor, and plasminogen activator inhibitor-1. The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe. With the exception of oxidized low-density lipoproteins, the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins. Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia. It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents.     

Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies

BACKGROUND: Ezetimibe (SCH 58235) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol. OBJECTIVE: Data from 2 multicenter, placebo-controlled, double-blind, randomized, parallel-group, 12-week studies of ezetimibe were pooled to evaluate the drug's effect on lipid parameters in patients with primary hypercholesterolemia. METHODS: After dietary stabilization (National Cholesterol Education Program Step I diet or a stricter diet), washout of lipid-altering drugs, and a 6-week placebo lead-in period, patients with baseline plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 130 and < or = 250 mg/dL and plasma triglyceride (TG) levels < or = 300 mg/dL were randomized to receive either ezetimibe 0.25, 1, 5, or 10 mg, or placebo administered once daily before the morning meal in study A (dose-response study) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B (dose-regimen study). RESULTS: A total of 432 patients were included in this pooled analysis, 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7% and 18.5%, respectively (P < 0.01 vs placebo) and significantly increased high-density lipoprotein cholesterol (hDL-C) levels by 2.9% and 3.5%, respectively (P < 0.05 vs placebo). A reduction in plasma TG levels was observed (P = NS). With the 10-mg dose of ezetimibe, 67.8% of patients achieved > or = 15% reduction in plasma LDL-C levels, and 22.0% achieved > or = 25% reduction. With the 5-mg dose, 54.0% of patients achieved > or = 15% reduction in plasma LDL-C levels, and 15.3% achieved > or = 25% reduction. The decrease in plasma LDL-C levels was significantly greater with ezetimibe 10 mg compared with ezetimibe 5 mg (P < 0.05). Ezetimibe was well tolerated, with an adverse event profile similar to that of placebo. Conclusions: In these two 12-week studies, ezetimibe significantly decreased plasma LDL-C levels and increased plasma HDL-C levels, with a tolerability profile similar to that of placebo.     

Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin

OBJECTIVE: To assess the effect of treatment with a St John's Wort product (Movina) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. DESIGN: Controlled, randomized, open, crossover pharmacodynamic study. SETTING: Two primary healthcare centres. Intervention. Patients were treated with Movina one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). SUBJECTS: Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10-40 mg daily) for at least three months. MAIN OUTCOME MEASURES: Assessments of total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. RESULTS: All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks' active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total-cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). CONCLUSION: Products containing St John's Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin.     

Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.

BACKGROUND: Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE: The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS: Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS: Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS: The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.     

A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA) combination tablet, relative to ezetimibe (EZE) and simvastatin (SIMVA) monotherapy, in patients with primary hypercholesterolemia. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, factorial design study After a 6- to 8-week washout period and 4-week, single-blind, placebo run in, hypercholesterolemic patients (low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides [TG], < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo. The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [CRP]. RESULTS: There were 1528 patients randomized to treatment (792 women, 736 men); mean (SD) age ranged from 54.9 (112) years to 56.4 (10.6) years across pooled treatment groups. The treatment groups were well balanced for baseline demographics. Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone (P < 0.001). Depending on dose, EZE/SIMVA was associated with reductions in LDL-C of -44.8% to -602%, non-high-density lipoprotein cholesterol of -40.5% to -55.7%, and TG of -22.5% to -30.7%; high-density lipoprotein cholesterol increased by 5.5% to 9.8%. EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone (P < 0.001). More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations <100 mg/dL (78.6% vs 45.9%; P < 0.001). EZE/SIMVA was generally well tolerated, with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal (ULN) (1 .5% for EZE/SIMVA and 1.1% for SIMVA; P = NS) or creature kinase levels > or =10 times ULN (0.0% for EZE/SIMVA and 02% for SIMVA; P = NS). CONCLUSION: The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia.     

辛伐他汀对高胆固醇血症患者RANTES表达的影响

目的 通过观察高胆固醇血症患者RANTES表达的变化及辛伐他汀对其表达变化的影响,探讨RANTES在动脉粥样硬化发生中的作用及他汀对其作用的影响.方法 2005年5月至2005年10月在我院健康查体中心随机选取健康对照60例和高胆固醇血症患者(血总胆固醇＞6.24mmol/L)80例,分别为对照组和高脂组;高脂组予以辛伐他汀20 mg·d-1,睡前口服,共12周,为他汀组.对照组、高脂组及他汀组治疗12周肘静脉取血,分离血清、血浆并提取单个核细胞.放射免疫法检测血浆的血管紧张素Ⅱ(AngⅡ)水平,实时定量RT-PCR和Western blot方法分别检测单个核细胞RANTES的mRNA和蛋白质表达水平.SPSS 12.0分析软件对试验的结果进行方差分析,Microsoft Excel对变量间的相关关系进行直线相关分析.结果 ①高脂组的血浆AngⅡ水平较对照组明显升高[(92.13±22.03) vs (50.85±12.12),P＜0.01],他汀组明显降低[(78.57±18.35) vs(92.13±22.27),P＜0.05].②高脂组单个核细胞RANTES的mRNA和蛋白质表达较对照组明显升高[(0.87±0.19) vs (0.23±0.05),P＜0.01和(1.17±0.22)对(0.38±0.09),P＜0.01],他汀组均明显降低[(0.46±0.11) vs (0.87±0.19),P＜0.01和(0.69±0.15) vs (1.17±0.22),P＜0.01].③高脂组AngⅡ与RANTES表达的相关分析显示,RANTES的表达与血浆的AngⅡ水平呈显著正相关(r=0.409,P＜0.01).结论 辛伐他汀下调高胆固醇血症患者单个核细胞RANTES表达的增高,高胆固醇血症患者单个核细胞RANTES表达的增高与血浆AngⅡ水平的增高有关.     

Fluvastatin/fenofibrate vs. simvastatin/ezetimibe in patients with metabolic syndrome: different effects on LDL-profiles

Background  Patients with metabolic syndrome (MS) and type 2 diabetes (T2DM) show increased risk for coronary artery disease. Lipoprotein metabolism is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) and predominance of atherogenic small, dense low-density lipoprotein (sdLDL), while low-density lipoprotein (LDL) cholesterol is only slightly elevated.
Methods  Multicentre, randomized, open-label cross-over study investigating the effect of combination of fluvastatin/fenofibrate (80/200 mg) (F&F) on LDL-subfractions compared with combination of simvastatin/ezetimibe (20/10 mg) (S&E) in patients with MS/T2DM.
Results  Seventy-five patients were randomized, 69 completed the study and LDL-subfractions of 56 patients were analysed. Thirty-eight out of 56 patients (68%) showed a profile dominated by sdLDL. In these, TG and total cholesterol (TC) were elevated compared with non-sdLDL patients. In all patients, reduction of TC and LDL cholesterol (LDL-C) by S&E was stronger than by F&F. The increase of HDL-C was stronger with S&E in the non-sdLDL group, whereas in the sdLDL group, there was no difference between treatments. In non-sdLDL patients, there was no effect on TG or LDL-radius. However, in the sdLDL group, F&F was more effective in reducing TG and increased LDL radius, whereas S&E reduced LDL radius even further.
Conclusions  S&E is more efficient in reducing TC and LDL-C. This is also true for HDL-C increase in non-sdLDL patients. However, in patients with sdLDL, F&F was more efficient in reducing TG and increasing LDL radius.     

辛伐他汀对高胆固醇血症患者动脉弹性的影响

目的探讨辛伐他汀对高胆固醇血症患者动脉弹性的影响。方法采用动脉弹性功能测定仪检测52例高胆固醇血症患者使用辛伐他汀前和使用4周后大动脉弹性（C1）、小动脉弹性（C2）和血浆总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）。结果用药4周后，TC和LDL-C均较用药前明显下降（均为P〈0．01），C1和C2较用药前明显升高（均为P〈0．01）。结论辛伐他汀可明显降低高胆固醇血症患者TC和LDL-C，同时显著改善动脉弹性。     

Comparison of the lipid-modifying efficacy and safety profiles of ezetimibe coadministered with simvastatin in older versus younger patients with primary hypercholesterolemia: a post Hoc analysis of subpopulations from three pooled clinical trials

BACKGROUND: Despite the need for effective and well-tolerated lipid-lowering therapies for primary hypercholesterolemia in older patients, there is a relative paucity of published data on such treatments in this population. OBJECTIVE: We conducted a post hoc analysis to examine the lipid-modifying efficacy and safety profile of simvastatin (SIMVA) monotherapy, and the coadministration of ezetimibe (EZE) and SIMVA (EZE/SIMVA) in older (ie, aged>or=65 years) versus younger (ie, aged<65 years) patients with primary hypercholesterolemia. METHODS: We analyzed pooled data from 3 previously published, similarly designed, randomized, double-blind, placebo-controlled studies in patients with primary hypercholesterolemia. After a 6- to 8-week washout, a 4-week dietary stabilization period, and a 4-week placebo run-in period, patients with low-density lipoprotein cholesterol (LDL-C) of 145 to 250 mg/dL were randomized to EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo for 12 weeks. In this post hoc analysis, the percent change from baseline to week 12 in LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein B (apo B), triglycerides (TG), and high-sensitivity C-reactive protein (hs-CRP) for EZE/SIMVA (pooled across doses) versus SIMVA alone (pooled across doses) was compared between older and younger patients with primary hypercholesterolemia. Tolerability was assessed by adverse event reports and laboratory and vital signs assessments throughout the study. RESULTS: A total of 3083 patients aged 20 to 87 years were included in the 3 studies (2320 were aged<65 years and 763 were aged>or=65 years). Baseline lipid values and patient characteristics were similar among all treatment groups for patients aged<65 years versus those aged>or=65 years except that there was a higher percentage of females (62% vs 50%) and patients with hypertension (46% vs 29%) in the older versus younger subgroup (both, P<0.001). EZE/SIMVA was associated with greater improvements than SIMVA alone in LDL-C, non-HDL-C, apo B, TG, and hs-CRP (all, P<0.001); these effects did not appear to differ between the older and younger sub-groups (all, P=NS). Changes in HDL-C did not differ significantly between the EZE/SIMVA and SIMVA groups. More patients receiving EZE/SIMVA than SIMVA monotherapy achieved the target LDL-C level<100 mg/dL (P<0.001), regardless of age subgroup (77% vs 41% for patients aged<65 years and 85% vs 48% for patients aged>or=65 years). In the younger sub-group, the incidence of creatinine phosphokinase (CK) elevations>or=10x the upper limit of normal (ULN) was or=10x ULN were reported. In younger patients, the incidence of consecutive alanine amino-transferase or aspartate aminotransferase levels>or=3x ULN was 0% for placebo and EZE, <1% for SIMVA, and 2% for EZE/SIMVA; in older patients, it was 1% for placebo and EZE, <1% for SIMVA, and 0% for EZE/SIMVA. CONCLUSION: This post hoc analysis of pooled data from 3 previously published large clinical trials suggests that EZE/SIMVA was well tolerated and associated with improved lipid profiles in both older and younger patients with primary hypercholesterolemia.     

Effects of orlistat, simvastatin, and orlistat + simvastatin in obese patients with hypercholesterolemia: a randomized, open-label trial

Background: Many obese patients have comorbidities that worsen their prognoses, particularly if hypercholesterolemia is present. In these patients, dietary restrictions are not sufficient to reduce hypercholesterolemia and lose body weight.Objective: This 1-year, single-center, randomized, open-label study assessed the effects of diet and exercise plus treatment with orlistat, simvastatin, and orlistat + simvastatin on lipid profile, body composition, and blood pressure in obese patients with hypercholesterolemia.Methods: Obese, normotensive patients with hypercholesterolemia aged > 45 years were eligible. Patients were prescribed a restricted-calorie diet and were randomized to receive orlistat 120 mg TID (group O), Simvastatin 20 mg/d (group S), or orlistat 120 mg TID plus simvastatin 20 mg/d (group OS) for 1 year. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels; body mass index (BMI); waist-circumference reduction (WCR); body weight loss (BWL); and diastolic blood pressure (DBF) and systolic blood pressure (SBP) were measured at baseline and after 6 months and 1 year of treatment.Results: We enrolled 87 patients (45 women, 42 men; mean age, 55 years). Four patients dropped out due to nontransient adverse events. After 1 year of treatment, significant improvements were found in all measured parameters in all treatment groups versus baseline values, except for HDL-C in group O. Significant between-group differences at 1 year included the following: TC, LDL-C, and TG levels and BMI, WCR, and BWL were significantly decreased in group OS versus groups O and S; DBP was significantly decreased in group OS versus group O; SBP and DBF were significantly decreased in group OS versus group S. HDL-C was significantly increased in group OS but not in groups O and S. Five patients in group O and 1 patient in group OS experienced transient gastrointestinal adverse events.Conclusions: In this study population, all 3 treatments produced significant improvements in most measured parameters from baseline. The combination treatment showed significantly greater reductions in serum TC and LDL-C levels, BMI, WCR, and BWL than with either orlistat or simvastatin alone. Small but significant differences in blood pressure were found with combination treatment.     

Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment

Background and objective: One of the problems associated with reaching the low‐density lipoprotein cholesterol (LDL‐C) target during statin treatment is the emergence of laboratory or clinical side effects. The aim of our study was to evaluate the prevalence of statin‐associated adverse events in diabetic and non‐diabetic patients affected by polygenic hypercholesterolemia or combined hyperlipidemia and the efficacy and tolerability of treatment with ezetimibe/simvastatin 10/10 mg/day on the same subjects experiencing the adverse events. Methods: Consecutively enrolment of patients affected by polygenic hypercholesterolemia or combined hyperlipidemia with or without type 2 diabetes mellitus. Each Centre used any of the available statins on the basis of current clinical judgement and monitored enrolled patients for adverse events during the following 2 years. Those patients with moderate adverse events suspended the current statin therapy for 1 month (washout period), and then were shifted to treatment with ezetimibe/simvastatin 10/10 mg/day and again monitored for adverse events in the following 6 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, total cholesterol, LDL‐C, high‐density lipoprotein cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine phosphokinase and monitored adverse events such as asthenia and myalgia. Results and discussion: All 1170 Caucasian patients affected by polygenic hypercholesterolemia obtained a significant reduction in LDL‐C during the observation period (P < 0·05), while those with combined hyperlipidemia also showed a reduction in TG plasma level (P < 0·05) and a significant increase in HDL‐C (P < 0·05). Patients affected by polygenic hypercholesterolemia experiencing adverse event under statin treatment obtained a significantly lower reduction than those tolerating the treatment (P < 0·001). The prevalence of adverse events under statin treatment was 4·9% in non‐diabetic patients with polygenic hypercholesterolemia, 8·6% in those with combined hyperlipidemia, 7·1% in diabetic patients with polygenic hypercholesterolemia and 7·6% in those with combined hyperlipidemia. Six months after the shift to treatment with ezetimibe/simvastatin 10/10 mg, all patients experienced a significant improvement in LDL‐C, TG and HDL‐C plasma level. No adverse event was registered during the ezetimibe/simvastatin 10/10 mg treatment period. It seems that previous side effects observed with statins did not re‐appear with the administration of ezetimibe/simvastatin 10/10 mg/day. Conclusions: The efficacy and adverse effect profile of the ezetimibe and simvastatin combination appear to be good for both diabetic and non‐diabetic patients, and in both conditions.     

Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia

We assessed pooled safety and lipid-regulating efficacy data from four similarly designed trials of ezetimibe coadministered with statins in 2382 patients with primary hypercholesterolemia. Patients were randomised to one of the following double-blind treatments for 12 weeks: placebo; ezetimibe 10 mg; statin; or statin + ezetimibe. Statin doses tested were 10, 20, 40 mg/day (atorvastatin, simvastatin, pravastatin or lovastatin) or 80 mg/day (atorvastatin, simvastatin). Treatment with ezetimibe + statin led to significantly greater reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and increases in HDL-C, compared to statin alone. At each statin dose, treatment with ezetimibe + statin led to a greater LDL-C reduction compared to the next highest statin monotherapy dose. Ezetimibe + statin had a safety profile similar to statin monotherapy. Coadministration of ezetimibe + statin offers a well-tolerated, highly efficacious new treatment strategy for patients with hypercholesterolemia.     

Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation.

Low density lipoprotein (LDL) apheresis is a treatment option for patients with severe hypercholesterolemia not adequately responding to drug treatment who have developed coronary heart disease. We regularly treated 18 patients with immunoadsorption, 8 with heparin induced extracorporeal LDL precipitation (HELP) and 8 with dextran sulfate adsorption for a mean of 4.6 +/- 2.6 years. The effects on LDL cholesterol, high density lipoprotein (HDL) cholesterol, and lipoprotein (a) were comparable among all 3 techniques. Twelve patients were treated for longer than 5 years and 18 patients for longer than 3 years. The evaluation of coronary angiograms (23 patients) revealed a definite regression of coronary lesions in 3 patients; in all other patients, there was a halt in progression. Three patients suffered a sudden cardiac death and 1 patient a nonfatal myocardial infarction due to the occlusion of a coronary bypass. In 9 of 11 patients, no atherosclerotic lesions developed in the coronary bypasses. No severe side effect of either procedure was observed. In conclusion, aggressive lipid lowering by LDL apheresis can stabilize coronary atherosclerosis in most patients.     

Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease

This randomised, double-blind, placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe (EZE) co-administered with ongoing atorvastatin (ATV) therapy in 450 hypercholesterolemic patients with coronary heart disease (CHD) who had not achieved their low-density lipoprotein cholesterol (LDL-C) goal < or =2.60 mmol/l while on a stable dose of ATV 10 or 20 mg/day for > or =6 weeks. After a 4-week diet/baseline active run-in period, patients with LDL-C >2.60 mmol/l and < or =4.20 mmol/l were stratified by ATV dose and randomised (1 : 1) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV. Significantly more patients achieved an LDL-C goal < or =2.6 mmol/l with EZE than PBO (81.3 vs. 21.8%; p < or = 0.001). Compared to PBO, co-administration of EZE with ongoing ATV led to significantly (p < or = 0.001) greater reductions in LDL-C, total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B; HDL-C was significantly (p < or = 0.05) increased. Co-administration of EZE and ATV was well tolerated, with an overall safety profile similar to ATV alone.     

家族性高胆固醇血症患者二例的LDLR基因复合杂合新突变分析

目的 探讨2例临床确诊的湖北籍FH患者的LDLR基因突变状况,为FH的基因诊断提供依据.方法 收集2例临床确诊的FH患者及其父母血脂检测指标等临床资料,通过PCR扩增LDLR基因的1～18个外显子和内含子区域,再将扩增产物进行正、反双向核苷酸序列分析,并与GenBank中LDLR基因的正常序列对比找出突变后,结合FH先证者的临床表型证实致病突变的类型.结果 氧化酶法测定1号、2号FH先证者血浆TC,分别为12.79、11.98 mmol/L;经核苷酸序列分析,其ApoB100基因涵盖的3 500～3 531区域均未见突变;LDLR基因均为复合杂合突变,1号FH先证者LDLR基因第4外显子的665位碱基G>T为杂合错义突变,且该突变为新的点突变,第9内含子的1 358+32位碱基C>T突变也为新的点突变,并均由其父母遗传.2号先证者第9外显子1 257位碱基C>A突变导致终止密码子提前出现,但其核苷酸改变与比利时报道的C>G不同,第13外显子检测到1 879位碱基G>A杂合错义突变,且分别来源于其父母.结论 2例FH先证者均存在LDLR基因复合杂合突变,1号FH先证者的第4外显子665位碱基G>T和第9内含子1 358+32位碱基C>T、2号FH先证者的第9外显子1 257位碱基C>A突变均为新突变,这可能是导致FH的分子机制.

Abstract：

Objective To determine LDLR gene mutation in 2 clinically diagnosed FH patients from Hubei province and provide basis for gene diagnosis of FH.Methods Clinical data of 2 FH patients and their parents were collected.The promoter region and exon 1 to exon 18 region of LDLR gene were amplified through PCR and the amplified products were analyzed by forward and reverse DNA sequencing.The mutations were identified after comparison with LDLR gene sequence in GenBank.The pathogenic gene mutations were confirmed according to both genotype and phenotype of FH probands.Results The levels of plasma TC of two probands were 12.79 and 11.98 mmol/L.respectively.No gene mutations were detected in region 3 500 to 3 531 of ApoB100. The mutations of LDLR gene were compound heterozygous mutations. The novel mutation 665G > T detected in the exon 4 of No. 1 proband's LDLR gene was heterozygous missense mutation. The novel mutation 1 358 +32C > T was detected in the exon 9 of No. 1 proband's LDLR gene.The mutations 665G > T ( paternal origin) and 1 358 + 32C > T ( maternal origin) were inherited from the parents. A novel mutation 1 257 C > A was detected in the exon 9 of No. 2 proband's LDLR gene, resulting the presence of a premature termination codon, which was different from 1 257 C > G reported in Belgium.Another heterozygous missense mutation 1 879 G > A was detected in exon 13. They were derived from paternal origin and maternal origin, respectively. Conclusions There are three novel gene mutations:665G >T, 1 358 +32C > T, 1 257C > A found in two probands with compound heterozygous mutations in LDLR respectively. They maybe play a potential role in FH pathogensis.