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.     

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of 相似文献   

Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial

OBJECTIVES: The aim of this research was to compare relative efficacy of different statin regimens in achieving the dual goals of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) reduction. BACKGROUND: While secondary prevention guidelines for statin therapy suggest lowering LDL-C levels <70 mg/dl, we have recently shown that clinical outcomes are improved when CRP levels are also lowered <2 mg/l. METHODS: We addressed the relative efficacy of pravastatin 40 mg and atorvastatin 80 mg daily to reduce LDL-C and CRP among 3,745 acute coronary syndrome patients. RESULTS: A total of 1,018 participants (27.1%) achieved the dual goals of LDL-C <70 mg/dl and CRP <2 mg/l. After adjustment for age, gender, smoking, diabetes, hypertension, obesity, and HDL-C, these individuals had a 28% lower risk of recurrent myocardial infarction or vascular death (relative risk = 0.72; 95% confidence interval 0.52 to 0.99). Of those who achieved dual goals, 80.6% received atorvastatin 80 mg, while 19.4% received pravastatin 40 mg (p < 0.001). Only 11% allocated pravastatin and 44% allocated atorvastatin achieved the goals of LDL-C <70 mg/dl and CRP <2 mg/l, and only 5.8% allocated pravastatin 40 mg and 26.1% allocated atorvastatin 80 mg reached the even lower goals of LDL-C <70 mg/dl and CRP <1 mg/l. The correlation coefficient for CRP measured at 30 days and at end of study was 0.61 (p < 0.001), a value almost identical to that for LDL-C over the same follow-up period (r = 0.62, p < 0.001). CONCLUSIONS: While atorvastatin 80 mg was superior to pravastatin 40 mg in terms of achieving the dual goals of aggressive LDL-C and CRP reduction, neither agent brought the majority of patients below thresholds needed to maximize patient benefit.     

Discovery Belux: comparison of rosuvastatin with atorvastatin in hypercholesterolaemia

METHODS: Discovery Belux is an open-label, multicentre, randomised, phase IIIb, parallel group study comparing the efficacy of rosuvastatin (RSV) and atorvastatin (ATV) on changes in lipid levels and the achievement of European Atherosclerosis Society (EAS) lipid goals. Patients (> or = 18 years) with primary hypercholesterolaemia, with a low-density lipoprotein (LDL-C) level > 120 mg/dl (on treatment) or > 135 mg/dl (naive subjects), and with a statin indication, were randomised to receive RSV 10 mg/day or ATV 10 mg/day for 12 weeks. Patients not at goal after 12 weeks and receiving ATV 10 were further switched to RSV 10 mg for another 12 weeks. Patients not at goal with RSV 10 mg were further titrated to RSV 20 mg. RESULTS: 938 patients were randomised to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving RSV 10 compared with ATV 10 achieved EAS LDL-C target goal (< 115 mg/dl) (85% vs. 67%). LDL-C was reduced by 47% and total cholesterol (TC) by 33% with RSV 10.This was 38% and 27% for ATV 10, respectively. After 24 weeks, an additional 57% of patients initially taking RSV 10 and uncontrolled, reached the target with RSV 20. In the patient group, initially taking ATV 10 and uncontrolled, 65% reached the target with RSV 10 after 24 weeks. Both treatments were well tolerated with a similar incidence of adverse events. In addition, a health economic analysis was performed. As RSV 10 is available at a lower cost in Belgium and as it is more effective, compared to ATV 10, it appeared to be the option of choice from a cost-effectiveness perspective. CONCLUSIONS: Rosuvastatin 10 mg treatment is significantly more effective than atorvastatin 10 mg at achieving European LDL-C goals, at lowering LDL-C and TC. These results were obtained with a similar safety profile. From a cost-effectiveness perspective RSV 10 is the preferred therapeutic option in comparison with ATV 10. Uptitration of uncontrolled patients to RSV 20 mg and switch from ATV 10 to RSV 10 allowed significantly more patients to reach the LDL-C and TC target goal.     

Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study

AIMS: To investigate whether selecting the starting dose of atorvastatin according to baseline and target (<2.6 mmol/L) LDL-cholesterol (LDL-C) values would allow high-risk subjects to achieve target LDL-C concentration within 12 weeks, with the initial dose or a single uptitration. METHODS AND RESULTS: Twelve-week, prospective, open-label trial that enrolled 2117 high-risk subjects (statin-free [SF] or statin-treated [ST]). Subjects with LDL-C >2.6 mmol/L (100mg/dL) but 相似文献   

Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH)

BACKGROUND: Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. METHODS AND RESULTS: We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C 相似文献   

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

OBJECTIVE: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. BACKGROUND: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. METHODS: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. RESULTS: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. CONCLUSIONS: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).     

Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study

OBJECTIVES: This study sought to determine if an aggressive, focused low-density lipoprotein cholesterol (LDL-C)-lowering strategy was superior to usual care for coronary heart disease (CHD) patients enrolled in health maintenance organization or Veterans Administration settings. BACKGROUND: Statin therapy benefits are well established. No prospective, randomized studies have tested strategies to optimize these benefits in a "real-world" setting. METHODS: A total of 2,442 CHD patients with hyperlipidemia were randomized to either an aggressive treatment arm using atorvastatin or usual care and followed for 51.5 months on average. Atorvastatin-group patients were titrated to LDL-C goals of <80 mg/dl (2.1 mmol/l) or a maximum atorvastatin dose of 80 mg/day. Usual-care patients received any treatment deemed appropriate by their regular physicians. End point assessments were complete in 958 atorvastatin-group and 941 usual-care patients. Partial assessments occurred in 259 patients in the atorvastatin group and 284 patients in the usual care group who did not complete four years of study participation because of adverse events, withdrawn consent, or follow-up loss. The primary efficacy parameter was time to first cardiovascular event. RESULTS: A total of 289 (23.7%) patients in the atorvastatin group compared with 333 (27.7%) patients in the usual care group experienced a primary outcome (hazard ratio, 0.83; 95% confidence interval 0.71 to 0.97, p = 0.02). This reduction in morbidity was largely due to fewer non-fatal myocardial infarctions (4.3% vs. 7.7%, p = 0.0002). Levels of LDL-C were reduced more (34.3% vs. 23.3%, p < 0.0001) and National Cholesterol Education Program goals (LDL-C <100 mg/dl) more likely met at end-of-study visits (72.4% vs. 40.0%) in patients receiving atorvastatin compared with those receiving usual care. CONCLUSIONS: An aggressive, focused statin therapy management strategy outperformed usual care in health maintenance organization and Veterans Administration clinic patients with CHD.     

Efficacy and safety of atorvastatin and pravastatin in patients with hypercholesterolemia

This 1-year, double-blind, active-controlled, multicenter study compared the efficacy and safety of atorvastatin to pravastatin and evaluated their ability to achieve target low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. Patients were stratified to risk factor groups based upon European Atherosclerosis Society (EAS) guidelines before randomization to atorvastatin 10 or 20 mg or pravastatin 20 or 40 mg once daily. Target LDL-C levels for patients with mild/moderate risk and severe risk were <130 mg/dl (3.4 mmol/l) and <115 mg/dl (3.0 mmol/l), respectively. If needed to achieve target levels both drugs were uptitrated within the approved dose range. Mean changes from LDL-C levels were 39% for atorvastatin patients compared to 29% for pravastatin-treated patients (p<0.0001). The number of patient responders (those reaching LDL-C goals) was higher (p<0.0001) for atorvastatin patients (91% at any study visit and 51% at the last study visit) than for pravastatin patients (48% and 20%, respectively). The daily atorvastatin dose used by most patients after the titration phase was 10 mg and the respective pravastatin dose was 40 mg. Both drugs were well-tolerated and had similar adverse event profiles. Atorvastatin, in the approved dose range, will allow a greater number of patients to reach established LDL-C treatment goals with single drug therapy.     

Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: results of the POLARIS study

POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients (n=871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for 26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks. Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and health economics. Mean LDL-C levels were reduced significantly more with rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (-56% versus -52%, p<0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8 weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%, p<0.01). Significant differences in the change from baseline in high-density lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I levels (+4.2 versus -0.5) were observed between rosuvastatin and atorvastatin (all p<0.05). Both treatments were well tolerated. Based on a US analysis, rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid-lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk patients with hypercholesterolemia.     

Rosuvastatin is cost-effective compared with atorvastatin in reaching cholesterol goals

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of coronary heart disease. The introduction of a highly efficacious new statin, rosuvastatin, may enable more patients to be treated to LDL-C goal within a fixed budget. OBJECTIVES: To compare the cost-effectiveness of rosuvastatin 10 mg and atorvastatin 10 mg in lowering LDL-C and achieving guideline goals after 12 weeks of treatment. The LDL-C goals were those recommended by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and the Third Joint European Task Force. METHODS: The analysis was performed on pooled data from three clinical trials. Efficacy was measured as the percent reduction in LDL-C and the proportion of patients who reached guideline LDL-C goals following the first 12 weeks of treatment, prior to dose titration. Costs comprised drug acquisition costs only. The cost-effectiveness measures were cost per 1% reduction in LDL-C and cost per patient treated to their LDL-C goal. RESULTS: Treatment with rosuvastatin 10 mg costs 1.85 per 1% reduction in LDL-C, compared with 2.37 per 1% reduction with atorvastatin 10 mg. The average costs per patient treated to the European LDL-C goals were 130.18 for rosuvastatin 10 mg and 242.44 for atorvastatin 10 mg. Treating to NCEP ATP III goals costs 115 per patient treated with rosuvastatin 10 mg vs. 163 per patient treated with atorvastatin 10 mg. CONCLUSIONS: Rosuvastatin has the same acquisition costs as and is more efficacious than atorvastatin in lowering LDL-C and treating patients to target LDL-C levels.     

Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients

We compared the effects of five different statins (atorvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin) on the lipid, lipoprotein, and apolipoprotein (apo) A-I-containing high-density lipoprotein (HDL) subpopulation profiles of 86 coronary heart disease (CHD) patients. Patients with established CHD, and low density lipoprotein (LDL) cholesterol (C)>130 mg/dl, and triglyceride (TG)<400 mg/dl, were treated with atorvastatin 20, 40, and 80 mg/day and one of the other four statins at 20, 40, and when available 80 mg/day in increasing doses (4 weeks of each dose) in a randomized crossover fashion. There was an 8-week placebo controlled washout period between different drug treatments. All five statins on each dose resulted in significant reductions in total- and LDL-C compared to placebo treatment. There were also decreases in plasma TG and increases in HDL-C and apoA-I concentrations, but not all treatments changed these parameters significantly. Each statin except fluvastatin improved the HDL subpopulation profile by increasing the concentrations of the large, cholesterol-rich, LpA-I alpha-1 and prealpha-1 HDL subpopulations. CHD patients have significantly lower concentration of the large, LpA-I alpha-1 HDL particles compared to controls. Our data indicate that statins which are the most effective in lowering LDL-C and TG are also the most effective agents in modifying the HDL subpopulation profile in CHD patients towards the patterns found in healthy individuals. The order of efficacy of statins in increasing alpha-1 HDL subpopulation was: atorvastatin, simvastatin, pravastatin, lovastatin and fluvastatin.     

A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDL-cholesterol

Lowering of serum cholesterol levels by pharmacologic intervention with statins reduces the incidence of cardiovascular events in subjects with and without atherosclerotic manifestations. In an 8-week, randomized, double-blind study we compared the efficacy and safety of the new compound atorvastatin for reducing LDL-cholesterol (LDL-C) with placebo in an Asian patient cohort. Patients with LDL-C between 160 mg/dl and 250 mg/dl were randomly assigned to treatment with 10 mg atorvastatin or placebo once daily for 8 weeks. At the end of weeks 4 and 8 of the randomized phase, the serum concentrations of lipid parameters as well as safety parameters were determined. Fifty-four patients (32 males and 22 females) were enrolled. Twenty-six patients were assigned to the treatment group. The primary end-point, LDL-C, was reduced by 40% and 42% after 4 and 8 weeks of treatment in the atorvastatin treated patients (p<0.001). The reductions in total cholesterol and triglycerides were up to 31% and 23%, respectively. The HDL-C levels increased up to 11% (p=0.043). There were no significant adverse events. Transient increases in CPK levels (10 times) without myalgia were identified in 1 patient. Atorvastatin, 10 mg/day produced significant reductions in LDL-C, total cholesterol and triglycerides and an elevation of HDL-C levels when used as an adjunct to diet in hyperlipidemic patients. The majority of the clinical effects could be attained by week 4. The overall safety profile of atorvastatin was similar to that of placebo. Atorvastatin was considered to be well tolerated in this patient cohort.     

Randomized evaluation of atorvastatin in patients with coronary heart disease: a serial intravascular ultrasound study.

BACKGROUND: It is unclear whether a marked reduction of low-density lipoprotein-cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild hypercholesterolemia leads to less progression of atherosclerosis. METHODS AND RESULTS: Patients with CHD and hypercholesterolemia (100相似文献   

Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects

The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subspecies were examined in a randomized, placebo-controlled fashion over 36 weeks in 97 patients with coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels of >130 mg/dl and compared directly with the effects of fluvastatin (n = 28), pravastatin (n = 22), lovastatin (n = 24), and simvastatin (n = 25). The effects of placebo and 40 mg/day of each statin were also examined in subjects with CHD with subjects in the fasting state and in the fed state 4 hours after a meal rich in saturated fat and cholesterol and compared with results in age- and gender-matched control subjects. At all doses tested in the fasting and fed states, atorvastatin was significantly (p <0.01) more effective in lowering LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol than all other statins, and significantly (p <0.05) more effective than all statins, except for simvastatin, in lowering triglyceride and remnant lipoprotein (RLP) cholesterol. At 40 mg/day in the fasting state, atorvastatin was significantly (p <0.01) more effective than all statins, except for lovastatin and simvastatin, in lowering cholesterol levels in small LDL, and was significantly (p <0.05) more effective than all statins, except for simvastatin, in increasing cholesterol in large HDL and in lowering LDL particle numbers. Our data indicate that atorvastatin was the most effective statin tested in lowering cholesterol in LDL, non-HDL, and RLP in the fasting and fed states, and getting patients with CHD to established goals, with fluvastatin, pravastatin, lovastatin, and simvastatin having about 33%, 50%, 60%, and 85% of the efficacy of atorvastatin, respectively, at the same dose in the same patients.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.     

Time as a variable with niacin extended-release/lovastatin vs. atorvastatin and simvastatin

Time may be an important variable when evaluating the efficacy of lipid-altering drugs. In this analysis of the Advicor Versus Other Cholesterol-Modulating Agents Trial Evaluation, niacin extended-release/lovastatin 1000/40 mg was as effective as atorvastatin 10 mg and more effective than simvastatin (both 10 mg and 20 mg) in achieving low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals. The titration schedule for this study included the initiation of niacin-extended release/lovastatin 500/20 mg once a day for 4 weeks, titrated to the starting dose of 1000/40 mg after 4 weeks, and then titrated to the final dose of 2000/40 mg. The titration schedule for both atorvastatin and simvastatin was 10 mg per day for 8 weeks and then titrated to 40 mg per day. Using this schedule, 50% of niacin extended-release/lovastatin and atorvastatin patients reached low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals within approximately 7 weeks, compared with simvastatin, in which 50% reached both treatment goals in 13-14 weeks. These time differences may have potential clinical relevance in reducing coronary heart disease risk.     

A comparative study with rosuvastatin in subjects with metabolic syndrome: results of the COMETS study.

AIMS: The efficacy and safety of rosuvastatin, atorvastatin, and placebo were compared in patients with the metabolic syndrome. METHODS AND RESULTS: Patients with the metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/L (130 mg/dL) and multiple risk factors conferring a 10-year coronary heart disease risk score of >10% were randomized (2:2:1) to receive rosuvastatin 10 mg, atorvastatin 10 mg, or placebo for 6 weeks. Subsequently, the rosuvastatin 10 mg and placebo groups received rosuvastatin 20 mg and the atorvastatin 10 mg group received atorvastatin 20 mg for 6 weeks. LDL-C was reduced significantly more in patients receiving rosuvastatin 10 mg when compared with those receiving atorvastatin 10 mg at 6 weeks [intention-to-treat (ITT) population by randomized treatment: 41.7 vs. 35.7%, P < 0.001; ITT population by as-allocated treatment: 42.7 vs. 36.6%, P < 0.001]. Significant LDL-C reductions were also observed in patients receiving rosuvastatin when compared with those receiving atorvastatin at 12 weeks (48.9 vs. 42.5%, P < 0.001). More patients achieved LDL-C goals with rosuvastatin when compared with atorvastatin. Rosuvastatin increased high-density lipoprotein cholesterol significantly more than atorvastatin. Treatments were well tolerated. CONCLUSION: At equivalent doses, rosuvastatin had a significantly greater effect than atorvastatin in lowering LDL-C and improving the lipid profile and was well tolerated in patients with the metabolic syndrome.     

不同调脂方案对冠心病患者C反应蛋白和CD40配体的影响

目的 观察在冠状动脉狭窄50%～70%的冠心病患者中应用阿托伐他汀和依折麦布联合治疗调脂作用和安全性,及其对C-反应蛋白(CRP)、CD40配体(CD40L)的影响. 方法选取冠状动脉狭窄50%～70%的冠心病患者42例,均未植入支架,分为他汀组19例(40 mg阿托伐他汀)和联合治疗组(10 mg阿托伐他汀+10 mg依折麦布)23例.在服药前、用药4周、用药12周测定总胆固醇(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、CRP和CD40L. 结果 (1)他汀组和联合治疗组均在4周时患者的TC、LDL-C降低,12周时他汀组的LDL-C为(1.94±0.49)mmol/L,联合治疗组为(1.92±0.54)mmol/L,两组差异无统计学意义;(2)他汀组和联合治疗组患者肝功能、肾功能、肌酸激酶用药后无明显升高;(3)两组CRP在12周时较基线均有降低,他汀组CD40L降低. 结论单用他汀治疗和联合治疗降脂疗效无差异.两种治疗均未引起患者肝、肾功能和肌酸激酶异常.40 mg阿托伐他汀治疗可降低患者CRP、CD40L.     

Reaching recommended lipid and blood pressure targets with amlodipine/atorvastatin combination in patients with coronary heart disease

The effects of combined atorvastatin and amlodipine on blood pressure (BP) and low-density lipoprotein (LDL) cholesterol levels were investigated in 134 patients with documented coronary heart disease treated for 1 year. BP at baseline was 128 +/- 15/79 +/- 9 mm Hg and was controlled by the treating physician; no calcium channel blockers were allowed. Baseline means for plasma cholesterol were 6.4 +/- 1.1 mmol/L (147 +/- 39 mg/dl), triglycerides 2.0 +/- 0.9 mmol/L (177 +/- 88 mg/dl), LDL cholesterol 4.4 +/- 1.0 mmol/L (170 +/- 39 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 +/- 12 mg/dl). Patients were all given atorvastatin 10 mg, then increased to 80 mg if the LDL cholesterol was <2.5 mmol/L (100 mg/dl). At 3 months, patients were randomized to amlodipine 10 mg or placebo. Plasma LDL cholesterol was decreased by 50%, and the LDL cholesterol target of <2.5 mmol/L was achieved in 81% of the patients. BP targets were achieved in 69% of the atorvastatin + placebo group, versus 96% in the atorvastatin + amlodipine group (p = 0.0002). With use of combination atorvastatin + amlodipine at doses ranging from 10 to 80 mg and 5 to 10 mg, respectively, recommended therapeutic goals were reached in most select subjects with coronary artery disease who were concomitantly receiving aspirin and antihypertensive therapy.