Effects of ezetimibe coadministered with simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients

OBJECTIVE: This study assessed the effect of coadministration of ezetimibe and simvastatin on high sensitivity C-reactive protein (hs-CRP) in a large subject cohort (N=1089). METHODS: Data were combined from two nearly identical prospective trials. After dietary stabilization, washout period, and placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.75-6.50 mmol/l and triglycerides (TG) < or =4.0 mmol/l were randomized to one of the following daily treatments for 12 weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the percent change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy cohorts. RESULTS: Ezetimibe coadministered with simvastatin more than doubled the hs-CRP reduction compared to simvastatin monotherapy (-33.3% versus -14.3%, p<0.01). At each individual simvastatin dose level, coadministration therapy exerted significant further incremental hs-CRP reductions compared to simvastatin monotherapy. Similar hs-CRP reductions with coadministered ezetimibe and simvastatin were observed in the major subgroups examined (coronary heart disease, gender, age, baseline LDL-C, and body mass index). CONCLUSION: In this large subject cohort, ezetimibe coadministered with simvastatin significantly reduced hs-CRP, suggesting a possible additional anti-inflammatory/anti-atherosclerotic action of combination therapy compared to simvastatin monotherapy.     

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia. BACKGROUND: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. METHODS: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo. CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.     

Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone.     

依泽替米贝联合辛伐他汀改善冠心病患者血脂水平的疗效

目的：评价依泽替米贝/辛伐他汀联合用药改善冠心病患者血脂水平的疗效.方法：稳定使用辛伐他汀20mg的182例冠心病患者按数字法被随机分为：联合用药组（90例,依泽替米贝10mg＋辛伐他汀20mg）,辛伐他汀组（92例,辛伐他汀40mg）.分别在治疗前,治疗后6周评估病人的低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、总胆固醇/高密度脂蛋白胆固醇比率（TC/HDL-C）、LDL-C＜2.6mmol/L的病人比例等指标.结果：与辛伐他汀组比较,联合用药组LDL-C（-15.9％比-27.6％）、TC（-10.46％比-18.7％）和TC/HDL-C（-9.7％比-19.4％）等指标下降幅度更显著,LDL-C＜2.6 mmol/L的比例（40.2％比74.4％）显著升高,P＜0.05～0.01.两组间不良反应事件发生率差别无显著性.结论：对于单独使用辛伐他汀治疗未能达到推荐低密度脂蛋白胆固醇治疗目标的患者来说,联合依泽替米贝是一种有效的治疗方案.     

Effect of combining psyllium fiber with simvastatin in lowering cholesterol

BACKGROUND: Soluble fiber supplements are recommended to reduce levels of low-density lipoprotein cholesterol (LDL-C). We evaluated the LDL-C-lowering effect of psyllium husk added to low-dose simvastatin therapy. METHODS: In a 12-week blinded placebo-controlled study, patients were randomized to receive 20 mg of simvastatin plus placebo, 10 mg of simvastatin plus placebo, or 10 mg of simvastatin plus 15 g of psyllium (Metamucil) daily. Levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were determined after 4 and 8 weeks of treatment. RESULTS: The study group comprised 68 patients. All treatments were well tolerated, and after 8 weeks the mean LDL-C levels in the group receiving 10 mg of simvastatin plus placebo fell by 55 mg/dL (1.42 mmol/L) from baseline, compared with 63 mg/dL (1.63 mmol/L) in the group receiving 10 mg of simvastatin plus psyllium (P = .03). The mean lowering of LDL-C in the group receiving 20 mg of simvastatin plus placebo was the same as that in the group receiving 10 mg of simvastatin plus psyllium. Similar results were seen for apolipoprotein B and total cholesterol. No significant changes from baseline triglyceride or high-density lipoprotein cholesterol levels occurred. CONCLUSIONS: Dietary psyllium supplementation in patients taking 10 mg of simvastatin is as effective in lowering cholesterol as 20 mg of simvastatin alone. Psyllium soluble fiber should be considered as a safe and well-tolerated dietary supplement option to enhance LDL-C and apolipoprotein B lowering.     

Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals

This study assessed whether the co-administration of ezetimibe and simvastatin would be more effective than simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of <100 mg/dl. Men and women with LDL cholesterol ≥130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: simvastatin 20 mg (n = 253), ezetimibe 10 mg plus simvastatin 10 mg (n = 251), ezetimibe 10 mg plus simvastatin 20 mg (n = 109), and ezetimibe 10 mg plus simvastatin 40 mg (n = 97). In all groups, patients not at goal had their simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (<100 mg/dl) after 5 weeks of treatment. Ezetimibe plus any dose of simvastatin produced greater reductions in LDL cholesterol and allowed more patients to achieve goal after 5 weeks (p <0.001) and at the end of the study (p <0.001) than simvastatin 20 mg alone. At 5 weeks, 75%, 83%, and 87% of patients receiving ezetimibe plus simvastatin 10, 20, and 40 mg had LDL cholesterol <100 mg/dl compared with 46% of patients receiving simvastatin 20 mg. In patients who started on ezetimibe plus simvastatin 10, 20 and 40 mg, 33%, 22%, and 12%, respectively, required simvastatin titration during the study compared with 68% of patients who started on simvastatin 20 mg. The corresponding median simvastatin doses used were 10, 20, 40, and 40 mg, respectively. Ezetimibe plus simvastatin was well tolerated, with an overall safety profile similar to that of simvastatin monotherapy. Thus, through the dual inhibition of cholesterol absorption and synthesis, ezetimibe plus simvastatin allowed more patients to reach LDL cholesterol <100 mg/dl at a lower simvastatin dose and with fewer dose titrations than simvastatin monotherapy.     

Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients

AIM: In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. METHODS: This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30-75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15-30 vs. 45 mg/day; rosiglitazone 2-4 vs. 8 mg/day). RESULTS: LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (-20.8%) than by doubling the dose of simvastatin to 40 mg (-0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. CONCLUSIONS: Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs.     

辛伐他汀对冠心病患者血管内皮细胞功能障碍的治疗作用（英文）

目的：研究辛伐他汀对冠心病患者血管内皮细胞功能障碍的干预作用。方法：90例冠心病患者按LDL-C水平分为三组：辛伐他汀20mg组（37例,LDL-C≥2.5mmol/L）,辛伐他汀10mg组（35例,2.5mmol/L〉LDL-C≥1.8mmol/L）,常规治疗组（18例,LDL-C〈1.8mmol/L,未服辛伐他汀）,疗程均为8周。应用彩色多普勒超声诊断仪测量受试者肱动脉血流介导的舒张功能（FMD）。应用硝酸还原酶法检测受试者一氧化氮（NO）的含量。常规检测血清TC、TG、LDL-C及HDL-C的浓度。结果：8周后,与治疗前比较,辛伐他汀20mg,10mg组TC、TG和LDL-C浓度明显下降（P均〈0.05）,而HDL-C明显升高（P均〈0.05）;辛伐他汀20mg组与10mg组间各指标差异无显著性（P〉0.05）;与常规治疗组比较,辛伐他汀20mg、10 mg组FMD[（6.01±0.49）%比（9.01±0.39）%比（9.01±0.47）%]明显改善（P均〈0.01）、血清NO含量[（38.97±8.89）μmol/L比（47.67±10.89）μmol/L比（45.61±9.09）μmol/L]明显升高（P均〈0.05）,辛伐他汀20mg、10 mg组两组间NO和FMD亦无显著差异（P〉0.05）。结论：辛伐他汀可增加冠心病患者一氧化氮含量,改善血管内皮细胞功能,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白可能有一定关系,但该作用无明显的量效关系,可能独立于降脂作用之外。     

Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia.

AIMS: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of ezetimibe 10 mg/day in patients with primary hypercholesterolemia. METHODS AND RESULTS: Following dietary stabilization, a 2-12-week washout period, and a 4-week, single-blind, placebo lead-in period, 827 patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/l (130 mg/dl) to < or =6.47 mmol/l (250 mg/dl) and triglycerides < or =3.95 mmol/l (350 mg/dl) were randomized 3:1 to receive ezetimibe 10 mg or placebo orally once daily in the morning for 12 weeks. The primary efficacy endpoint was percentage reduction in direct plasma LDL-C. Ezetimibe reduced direct LDL-C by a mean of 17.7% from baseline to endpoint, compared with an increase of 0.8% with placebo (P<0.01). Response to ezetimibe was generally consistent across all subgroups analyzed. Ezetimibe also significantly improved levels of plasma total cholesterol, apolipoprotein B, high-density lipoprotein(2)-cholesterol and lipoprotein(a), and elicited a trend toward lower triglyceride levels. Ezetimibe did not alter the serum concentrations of lipid-soluble vitamins or significantly affect baseline or stimulated cortisol production. Ezetimibe was well tolerated, with a safety profile similar to that of placebo. CONCLUSIONS: Ezetimibe, which significantly reduces LDL-C and favorably affects other lipid variables, may provide a well tolerated and effective new option for lipid management in the future.     

Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels

Data pooled from 21 atorvastatin clinical trials have been analyzed to establish the safety of reducing low density lipoprotein cholesterol (LDL-C) levels below currently recommended minimum targets in hypercholesterolemic patients. Safety data for atorvastatin-treated patients with at least one LDL-C value < or =80 mg/dl (2.1 mmol/l) (n = 319) during treatment (mean LDL-C level throughout treatment was 91 mg/dl [2.4 mmol/l]) were compared to those from all atorvastatin-treated patients (n = 2502) and patients treated with lovastatin, simvastatin or pravastatin (n = 742). The frequency of treatment-associated adverse events (AEs) in the atorvastatin LDL-C < or =80 mg/dl (2.1 mmol/l) subgroup (24%) was comparable to the frequencies observed for all atorvastatin-treated patients (20%) and for patients receiving the other statins (24%). Patient withdrawals due to treatment-associated AEs (constipation, dyspepsia and flatulence being the most common) were consistent and low across treatment groups. No treatment-associated deaths occurred in any group. Safety data for 21 atorvastatin-treated patients with LDL-C < or =50 mg/dl (1.3 mmol/l) were also analyzed and found to be similar to all atorvastatin-treated patients and patients treated with the other statins. While recognizing the short-term nature of the data (all patients who received atorvastatin were treated for < or =1 year and approximately 30% were treated for < or =6 months), this analysis suggests that reducing LDL-C levels below 80 (2.1 mmol/l) or 50 mg/dl (1.3 mmol/l) with atorvastatin does not alter its safety profile, as measured by frequency of AEs, which remains similar to those of other statins.     

依折麦布联合辛伐他汀对冠心病及糖尿病患者的血LDL-C达标和安全性观察

目的 观察依折麦布联合辛伐他汀对冠心病及糖尿病患者血LDL-C达标率和安全性。方法选择血LDL-C未达标的冠心病及糖尿病患者46例,随机分成依折麦布（10mg/d）联合辛伐他汀（20mg/晚）组（联合治疗组）24例和他汀加倍治疗组22例（给予辛伐他汀40mg/晚）。观察两组患者降脂药物治疗后血脂水平变化及第4周、8周、12周时患者血LDL-C达标率、药物不良反应等。结果在降脂治疗第4、8和12周,联合用药组血LDL-C达标率均高于他汀加倍治疗组,第8、12周时两组患者达标率比较有显著统计学差异（P〈0.01）。药物治疗12周时,两组患者血脂水平较治疗前均有改善,血LDL-C和TC水平与同组治疗前比较差异有统计学意义（P〈0.01～0.05）;两组患者药物治疗12周后血LDL-C和TC水平比较亦有显著统计学差异（P〈0.01）。联合用药组患者均能耐受降脂治疗,他汀加倍治疗组中有2例（9.1%）患者因不良反应出现减量或停药。结论依折麦布联合辛伐他汀治疗较单纯加大辛伐他汀剂量治疗更能提高患者血LDL-C达标率,且具有良好耐受性。     

依折麦布联合辛伐他汀对冠心病患者的调脂作用

目的:探讨依折麦布联合辛伐他汀对冠心病患者血脂及炎性因子的调节作用。方法: 选取2011年5月~9月我院收治的冠心病患者60例,随机分为试药组和对照组,每组各30例,试药组采用依折麦布(10 mg/d)联合辛伐他汀(20 mg/d),对照组单独使用辛伐他汀（40 mg/d）。在服药前、用药4周、用药8周时分别测定总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肝功能、肾功能、肌酸激酶(CK)。结果: 与用药前基线水平相比,两组用药4周TC、LDL-C水平均显著下降（P<0.05）,治疗8周均进一步下降（P<0.01）,并且与对照组相比,试药组8周TC、LDL-C下降水平更显著（P<0.05）。两组患者的肝功能、肾功能、CK在用药后均无明显异常。结论: 依折麦布联合辛伐他汀能更有效地降低冠心病患者血脂水平。     

Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study

BACKGROUND: Rosuvastatin (Crestor), a new, highly efficacious statin, has demonstrated dose-dependent low-density lipoprotein cholesterol (LDL-C) reductions of up to 65% in a dose-ranging programme with doses of 1 to 80 mg. DESIGN: A randomized, double-blind multicentre trial compared rosuvastatin with commonly used starting doses of pravastatin and simvastatin to determine relative efficacy in LDL-C reduction and impact on other lipid parameters in primary hypercholesterolaemia. METHODS AND RESULTS: A total of 502 patients (greater-than-or-equal 18 years; LDL-C greater-than-or-equal 4.14 mmol/l [160 mg/dl] and < 6.50 mmol/l [250 mg/dl] and triglycerides less-than-or-equal 4.52 mmol/l [400 mg/dl]) were randomized to 12 weeks of rosuvastatin 5 mg (n = 120) or 10 mg (n = 115), pravastatin 20 mg (n=]137) or simvastatin 20 mg (n = 130). Rosuvastatin 5 and 10 mg reduced LDL-C by 42 and 49%, respectively, compared with 28% for pravastatin (P < 0.001 versus both rosuvastatin doses) and 37% for simvastatin (P < 0.01 versus rosuvastatin 5 mg; P < 0.001 versus 10[?]mg). National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP II) goals were achieved by 87% of rosuvastatin 10[?]mg patients, 71% of rosuvastatin 5[?]mg patients, 53% of pravastatin patients, and 64% of simvastatin patients; similar proportions of patients achieved NCEP ATP III goals. European Atherosclerosis Society (EAS) goals were achieved by 83, 63, 20 and 50% of patients, respectively. All study treatments were well tolerated. CONCLUSIONS: Both doses of rosuvastatin were more effective than pravastatin and simvastatin in meeting NCEP ATP II and EAS LDL-C targets. Rosuvastatin 10 mg was more effective than pravastatin and simvastatin in meeting NCEP ATP III targets.     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

不同剂量辛伐他汀调脂治疗冠心病的疗效及安全性研究

目的　观察冠心病 (CHD)患者中 ,辛伐他汀不同剂量调脂的有效性和安全性。方法　选择确诊为CHD的 114例患者 ,随机 (计算机数字表 )、开放分为辛伐他汀 2 0mg组 (n =5 8)和 10mg组 (n =5 6 ) ,年龄 40～ 86岁 ,平均年龄(6 0 .7± 9.7)岁。均为每晚服药 1次。分别于用药前、用药后第 6、12、2 4周空腹采静脉血清 ,以酶法测定总胆固醇(TC)、低密度脂蛋白胆固醇 (LDL C)、高密度脂蛋白胆固醇 (HDL C)、甘油三酯 (TG)以及肝、肾功能等。结果　 (1)用药第 6周始 ,两组TC和LDL C均比用药前明显下降 ,且一直保持到用药 2 4周末 (P均 <0 .0 5 )。 (2 )第 6、12、2 4周的TC、LDL C水平 ,在 2 0mg组比 10mg组明显低 (P <0 .0 5 )。 (3) 2 4周TC达标率 ,2 0mg组明显高于 10mg组(78.2 %比 5 2 .9% ,P <0 .0 5 )。 (4 )两组间谷丙转氨酶 (ALT)升高等副作用未见明显差异。结论　 2 0mg辛伐他汀能够安全而且更有效地降低TC和LDL C水平 ,使更多的CHD患者的血清胆固醇达到理想标准水平     

Efficacy and safety of ezetimibe/simvastatin co- administered with fenofibrate in mixed hyperlipidemic patients with metabolic syndrome

Background: We compared the lipid-altering effects of ezetimibe/simvastatin (EZE/SIMVA) co-administered with fenofibrate (FENO) in mixed hyperlipidemic patients with (MetS) versus those without MetS. Methods: A total of 611 patients, 20 to 79 years old, with LDL-C 130-220 mg/dL (100-180 mg/dL for patients with type 2 diabetes [T2D]), triglycerides (TG) 150-500 mg/dL, and no history of CHD or other CHD risk equivalent disease (except for T2D), were randomized in a 1:3:3:3 ratio into one of the following four treatments for 12 weeks: placebo; EZE/SIMVA 10/20 mg; FENO 160 mg; or EZE/SIMVA+FENO. MetS status was determined in 607 patients using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), TG, apolipoproteins A-I and B, and C-reactive protein was assessed in these patients with or without MetS. The primary objective was to evaluate the lipid-altering efficacy of EZE/SIMVA+FENO versus FENO monotherapy in the MetS versus non-MetS subgroups. Results: At baseline, patients with MetS had a higher body mass index (BMI) and TG and lower HDL-C. At Week 12, treatment with EZE/SIMVA, FENO, and EZE/SIMVA + FENO led to similar improvements in lipid parameters in patients with MetS compared to those without MetS. Treatment with EZE/SIMVA + FENO and FENO also led to an increase in LDL particle-size pattern after 12 weeks in both subgroups of patients. Conclusions: This post-hoc analysis suggested that co-administration of EZE/SIMVA+FENO had consistent benefits on the lipid profile in mixed hyperlipidemic patients with or without MetS.     

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained ≥3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P<0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of <3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P<0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.     

Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia

This study compared the efficacy and safety of co-administered ezetimibe + simvastatin with atorvastatin monotherapy in adults with hypercholesterolemia. Seven hundred eighty-eight patients were randomized 1:1:1 to 3 treatment groups; each group was force-titrated over four 6-week treatment periods: (1) 10 mg of atorvastatin as the initial dose was titrated to 20, 40, and 80 mg; (2) co-administration of 10 mg of ezetimibe and 10 mg of simvastatin (10/10 mg) was titrated to 10/20, 10/40, and 10/80 mg of ezetimibe + simvastatin; and (3) co-administration of 10/20 mg of ezetimibe + simvastatin was titrated to 10/40 mg (for 2 treatment periods) and 10/80 mg of ezetimibe + simvastatin. Key efficacy measures included percent changes in low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) from baseline to the ends of (1) treatment periods 1 and 2 (for LDL cholesterol) comparing co-administration of 10/20 mg and 10/10 mg of ezetimibe + simvastatin with 10 mg of atorvastatin and (2) treatment period 4 (for LDL cholesterol and HDL cholesterol) comparing co-administration of 10/80 mg of ezetimibe + simvastatin with 80 mg of atorvastatin. Baseline LDL and HDL cholesterol levels were comparable between treatment groups. At the end of treatment period 1, the mean decrease of LDL cholesterol was significantly (p ≤0.001) greater for co-administration of 10/10 mg and 10/20 mg of ezetimibe + simvastatin than for 10 mg of atorvastatin. At the end of treatment period 4 and after comparing maximum doses, co-administration of 10/80 mg of ezetimibe + simvastatin was superior to 80 mg of atorvastatin in the percent LDL cholesterol decrease (−59.4% vs −52.5%, p <0.001) and HDL cholesterol increase (12.3% vs 6.5%; p <0.001). All treatments were well tolerated. Thus, a greater LDL cholesterol decrease and HDL cholesterol increase were attained by treating patients with co-administration of ezetimibe and simvastatin than with atorvastatin.     

Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia

BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) have a high incidence of cardiovascular morbidity and mortality from premature atherosclerosis, and the efficacy of pharmacological therapy has been limited. We evaluated the efficacy, safety, and tolerability of ezetimibe, a novel cholesterol absorption inhibitor, in a multicenter, double-blind, randomized trial of HoFH patients receiving atorvastatin or simvastatin. Methods and Results- Fifty patients with a diagnosis of HoFH on the National Cholesterol Education Program Step 1 or stricter diet and taking open-label atorvastatin 40 mg/d or simvastatin 40 mg/d (statin-40) with (n=25) or without (n=25) concomitant LDL apheresis were randomized to 1 of 3 double-blind treatments: atorvastatin or simvastatin 80 mg/d (statin-80, n=17); ezetimibe 10 mg/d plus atorvastatin or simvastatin 40 mg/d (n=16); or ezetimibe 10 mg/d plus atorvastatin or simvastatin 80 mg/d (n=17) for 12 weeks. The primary end point was mean percentage change in LDL cholesterol (LDL-C) from statin-40 baseline to the end point for patients receiving statins alone (statin-80) versus patients receiving ezetimibe plus atorvastatin or simvastatin at either dose (ezetimibe plus statin-40/80). Ezetimibe plus statin-40/80 significantly reduced LDL-C levels compared with statin-80 (-20.7% versus -6.7%, P=0.007). In the high-dose statin cohorts, ezetimibe plus statin-80 reduced LDL-C by an additional 20.5% (P=0.0001) versus statin-80. Similar significant reductions in LDL-C concentrations were observed for patients with genotype-confirmed HoFH (n=35). Ezetimibe was safe and well tolerated. CONCLUSIONS: Ezetimibe coadministered with atorvastatin or simvastatin in patients with HoFH produced clinically important LDL-C reductions compared with best current therapy. Ezetimibe provides a new, complementary pharmacological approach for this high-risk population.     

匹伐他汀钙治疗老年冠心病患者42例的疗效

目的：观察匹伐他汀钙治疗老年冠心病患者的疗效及安全性。方法：入选82例口服辛伐他汀10～20mg至少一年的老年冠心病患者,入院后随机分为辛伐他汀组（40例：继续服用辛伐他汀）和匹伐他汀组（42例,改为每晚睡前口服匹伐他汀钙1-2mg）,疗程为8周。分别于用药前、用药后2、4、8周检测两组肝功、血脂、磷酸肌酸激酶变化,并进行比较。结果：匹伐他汀钙组总胆固醇（Tc）和低密度脂蛋白-胆固醇（LDL—c）水平的下降与辛伐他汀片10～20mg／d相当[TC（4．31±0．67）mmol／L比（4．32±0．65）mmol／L,LDL—C（2．15±0．56）mmol／L比（2．05±0．78）mmol／L],P均〉0．05。不良反应较轻微,仅辛伐他汀组出现3例谷丙转氨酶、谷草转氨酶水平升高,在治疗4周时其值均明显高于匹伐他汀组（P〈0．05）。结论：匹伐他汀钙对老年冠心病患者疗效及安全性均较好,对肝功损害较轻。