Rosuvastatin reduces intima-media thickness in hypercholesterolemic subjects with asymptomatic carotid artery disease: the Asymptomatic Carotid Atherosclerotic Disease in Manfredonia (ACADIM) Study

Background: An increase in carotid intima-media thickness (CIMT) represents an early phase of the atherosclerotic process. The aim of this study was to evaluate whether a reduction in CIMT could be seen with only 16 weeks of treatment with rosuvastatin (10 mg/day). Methods/results: Sixty-six participants of the ACADIM Study with hypercholesterolemia and carotid atherosclerosis at baseline carotid ultrasound investigation (CUI) were examined, with repeat CUI after 16 weeks of treatment. Demographic and lifestyle data were collected, as well as physical examination and fasting venous blood samples. Total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides decreased significantly (p < 0.0001), while high density lipoprotein cholesterol (HDL-C) increased significantly (p < 0.0001) during the intervention. The mean decrease in IMT of the right and left common carotid arteries (CCAs) was 0.35 and 0.38 mm, respectively (p < 0.05 for each). Age and lipid profile parameters were significant predictors of change in CIMT in linear regression analyses after adjustment for established atherosclerosis risk factors. Conclusions: Treatment with rosuvastatin in adults with evidence of subclinical atherosclerosis significantly reduced the CIMT of both CCAs, as well as improving lipid and lipoprotein levels.     

Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy*

SUMMARY

Objective: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial.

Methods: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5?mg, 10?mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12.

Results: Rosuvastatin 5?mg and 10?mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (?p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5?mg and 10?mg, respectively, vs. –0.5% for placebo; p < 0.001), as did Apo A-I levels (?p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported.

Conclusions: Rosuvastatin 5?mg or 10?mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.     

The Effect of Short-term Lipid Lowering with Atorvastatin on Carotid Artery Intima Media Thickness in Patients with Peripheral Vascular Disease: A Pilot Study

Summary

The effect of rapid lipid lowering (with 20?mg/day of atorvastatin) on common carotid artery intima media thickness (IMT) in patients (n = 12) with peripheral vascular disease was studied. Fasting blood samples and IMT measurements were carried out at baseline and repeated after 8 weeks’ treatment. Total cholesterol decreased significantly by 27% (p < 0.0005) and low-density lipoprotein (LDL) cholesterol by 41% (p < 0.001). The rapid reduction in lipid profiles was mirrored by a significant (p < 0.001) reduction of 15.3% in common carotid artery IMT.     

The effects of rosuvastatin alone or in combination with fenofibrate or omega 3 fatty acids on inflammation and oxidative stress in patients with mixed dyslipidemia

Objective: Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia.

Methods: Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group RΩ). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment.

Results: Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RΩ, respectively). This decrease was greater in the R and RF groups compared with the RΩ combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RΩ groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2α levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RΩ groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RΩ, respectively). No significant changes were observed in PON activities in all treatment groups.

Conclusion: The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia.     

The effect of 24 months of combination statin and extended-release niacin on carotid intima‐media thickness: ARBITER 3

ABSTRACT

Objective: The ARBITER 2 trial showed that extended-release niacin (ERN) when added to statin monotherapy slowed the progression of carotid atherosclerosis over 12 months. Whether longer treatment with ERN would have a greater effect on carotid intima.media thickness (CIMT) is unknown.

Research design and methods: We examined the long-term effects of ERN on high density lipoprotein (HDL-C) cholesterol and CIMT during 12.24 months treatment with ERN in ARBITER 2 participants who were either continued or were crossed over (from placebo) to ERN 1000?mg daily.

Main outcome measures: Among 149 subjects completing ARBITER 2, 130 (88%) enrolled in ARBITER 3. The prespecified primary endpoints were the within-group change in CIMT and HDL.C in patients receiving placebo for 12 months (n = 71), ERN for 12 months (comprised of subjects from ERN treatment during ARBITER 2 (n = 78) and those crossed over to ERN from placebo after ARBITER 2 (n = 47)), and ERN for 24 months spanning ARBITER 2 and 3 (n = 57). Five subjects discontinued the study due to flushing side effects. The study was completed by 104 subjects (47 crossed over from placebo; 57 with ERN continued from ARBITER 2).

Results: HDL.C increased in the ERN group from 39.5 ± 6.7 to 48.6 ± 13.3?mg/dl (p < 0.001) along with modest reductions in LDL.C and TG. Among 125 participants treated with ERN for 12 months, there was a net regression of CIMT of. 0.027 ± 0.011?mm (p < 0.001 vs. placebo). Among 57 participants treated with ERN for 24 months, there was additional significant regression of CIMT of. 0.041 ± 0.021?mm (p = 0.001 vs. placebo). Controlling for changes in LDL and triglycerides, only changes in HDL.C were independently associated with regression of CIMT (b =. 0.25; p = 0.001).

Conclusion: When added to statin therapy, ERN significantly increases HDL.C and induces atherosclerosis regression measured by CIMT over 24 months. Limitations to this study include its open-label design and the inability to relate CIMT effects to clinical outcomes.     

Attainment of optional low-density lipoprotein cholesterol goal of less than 70 mg/dl and impact on prognosis of very high risk stable coronary patients: a 3-year follow-up

Objectives: We aimed to investigate the proportion of very high-risk patients with coronary heart disease (CHD) who achieve the optional low-density lipoprotein cholesterol (LDL-C) target of < 70 mg/dl (1.8 mmol/liter), the factors that influence the success rate and the impact on their prognosis.

Research design and methods: We enrolled 1337 consecutive patients with stable CHD. Fasting lipids were determined and all cardiovascular events were recorded during a median follow-up of 33 months.

Results: The majority (86.5%) of patients were taking lipid-lowering medication (95.5% statins), but only 50.6% had LDL-C levels of < 100 mg/dl (2.6 mmol/liter). In total, 941 (70.4%) patients were considered very high risk and only 15.1% of them had LDL-C levels of < 70 mg/dl. Τhe use of intensive lipid-lowering medication was associated with 12-fold (95% CI 6.98 – 20.76; p < 0.001) higher possibility in achieving LDL-C levels of < 70 mg/dl. Attainment of LDL-C levels of < 70 mg/dl by patients at very high risk were independent predictors of all cardiovascular events (HR = 0.34, 95% CI 0.17 – 0.70; p = 0.003).

Conclusions: The vast majority of very high-risk patients do not achieve the optional LDL-C goal; this is mainly due to the suboptimal uptitration of statin dose and is translated into loss of clinical benefits.     

LDL‐C/HDL‐C ratio in subjects with cardiovascular disease and a low HDL‐C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study

ABSTRACT

Background: The ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL‐C/HDL‐C) is a reliable predictor of cardiovascular risk. Low HDL‐C levels in patients with coronary artery disease are associated with a high risk for cardiovascular events.

Objectives: This study compared the effects of rosuvastatin and atorvastatin on the LDL‐C/HDL‐C ratio in patients with cardiovascular disease and low HDL‐C.

Methods: Patients aged 40–80 years with established cardiovascular disease and HDL‐C < 1.0?mmol/L (< 40?mg/dL) entered a 6‐week dietary run-in period, before randomisation to open-label treatment with rosuvastatin 10?mg (n = 230) or atorvastatin 20?mg (n = 231) for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20?mg or atorvastatin 40?mg, and after 12 weeks to rosuvastatin 40?mg or atorvastatin 80?mg. Serum lipid parameters were measured at baseline and 6, 12 and 18 weeks.

Results: After 6 weeks of treatment, mean percentage change from baseline in LDL‐C/HDL‐C ratio was –47.0% in the rosuvastatin group and –41.9% in the atorvastatin group (?p < 0.05 for between-group comparison). After 12 and 18 weeks of treatment, change from baseline was –53.0% and –57.3%, respectively, for rosuvastatin, compared with –47.9% and –49.6%, respectively, for atorvastatin (?p < 0.01 and p < 0.001, respectively, for between-group comparison). Rosuvastatin also reduced LDL‐C, total cholesterol and non-HDL‐C significantly more than atorvastatin at all three time points, and significantly improved total cholesterol/HDL‐C and apolipoprotein B/A‐I ratios.

Conclusions: Rosuvastatin 10, 20 and 40?mg is significantly more effective than atorvastatin 20, 40 and 80?mg, respectively, in improving the LDL‐C/HDL‐C ratio in patients with cardiovascular disease and low HDL‐C. Further studies are required to clarify the benefits of rosuvastatin for reduction of cardiovascular risk.     

Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients

ABSTRACT

Objective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.

Research design and methods: Double-blind, multicenter, 6‐week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10?mg/day), the next highest (10/40 or 20?mg/day), and maximum doses (10/80 or 40?mg/day).

Results: At all doses and across doses, ezetimibe/simvastatin reduced LDL‐C levels significantly more (52–61%) than rosuvastatin (46–57%; p ≤ 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p ≤ 0.005) attained LDL‐C levels < 70?mg/dL (1.8?mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (?p < 0.001), non-high-density lipoprotein cholesterol (?p < 0.001), lipid ratios (?p ≤ 0.003), and apolipoprotein B (?p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (?p = 0.004) and next highest (?p = 0.006) doses, and across all doses (?p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10?mg versus 10/20?mg/day (?p = 0.004) and 40?mg versus 10/80?mg/day (?p < 0.001).

Conclusion: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL‐C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies.     

The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL‐C Value – an Evaluation of Rosuvastatin therapY compared with atorvastatin

ABSTRACT

Background: International guidelines emphasize the need to achieve recommended low-density lipoprotein cholesterol (LDL‐C) levels in order to reduce morbidity and mortality associated with coronary heart disease (CHD). However, many patients with hypercholesterolemia fail to achieve LDL‐C goals on treatment.

Objective: The primary objective was to compare the efficacy of rosuvastatin and atorvastatin for enabling patients to achieve National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL‐C goals. Secondary objectives were European LDL‐C goal achievement, changes in the lipid profile, and safety.

Research design and methods: This 12‐week, multicenter, multinational, randomized, open-label trial compared the efficacy and safety of rosuvastatin 10?mg with atorvastatin 10?mg in statin-naïve and switched patients with primary hypercholesterolemia from Brazil, Colombia, Mexico, Portugal, and Venezuela.

Results: A total of 1124 patients with similar baseline characteristics were randomized to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving rosuvastatin 10?mg compared with atorvastatin 10?mg achieved NCEP ATP III LDL‐C goals (71.2% vs 61.4%, p < 0.001), 1998 European LDL‐C goals (73.5% vs 59.2%, p < 0.001) and 2003 European LDL‐C goals (58.9% vs 44.6%, p < 0.001). Rosuvastatin treatment was associated with significant reductions in LDL‐C and total cholesterol (TC) and, in statin-naïve patients, a significant increase in high-density lipoprotein cholesterol (HDL‐C) compared with atorvastatin treatment. Both treatments were well tolerated with a similar incidence of adverse events. Clinically significant elevations in creatinine, creatine kinase or hepatic transaminases were low and similar between treatment groups.

Conclusions: Rosuvastatin 10?mg is significantly more effective at achieving NCEP ATP III and European LDL‐C goals, lowering LDL‐C and TC in both naïve and switched patients and increasing HDL‐C in naïve patients than atorvastatin 10?mg, with a similar safety and tolerability profile. This study also provides evidence regarding the comparative effects of rosuvastatin versus atorvastatin in Latin American and Portuguese populations.     

Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002)

SUMMARY

This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p?<?0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio?=?2.45, p?<?0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the post-menopausal status (hazard ratio?=?0.26, p?<?0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio?=?1.17, p?<?0.05); hypertension increased the risk for an adverse event (hazard ratio?=?3.02, p?<?0.05) and a 1?mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio?=?1.04, p?<?0.05).

With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH.     

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

ABSTRACT

Objective: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity.

Methods: We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study – RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40–80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL?C) < 1.0?mmol/L (< 40?mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10?mg or atorvastatin 20?mg daily for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20?mg or atorvastatin 40?mg and after 12 weeks to rosuvastatin 40?mg or atorvastatin 80?mg daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks.

Results: After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39?U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84?U/L, p = 0.77). The difference between groups did not reach significance (?p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (?p = 0.0001) and similar increases in HDL?C after 6 weeks [0.06?mmol/L (2.32?mg/dL) vs. 0.05?mmol/L (1.93?mg/dL)] and after 18 weeks [0.10?mmol/L (3.87?mg/dL) vs. 0.10?mmol/L (3.87?mg/dL)].

Conclusions: Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin.     

氯吡格雷联合阿托伐他汀钙治疗高血压合并颈动脉粥样硬化的疗效观察

目的探讨氯吡格雷联合阿托伐他汀钙治疗高血压合并颈动脉粥样硬化的临床疗效。方法选取2011年1月—2014年12月江阴市中医院收治的高血压合并颈动脉粥样硬化患者120例,随机分为对照组和治疗组,每组各60例。对照组在常规治疗的基础上口服阿托伐他汀钙片20 mg/次,1次/d。治疗组在对照组的基础上口服硫酸氢氯吡格雷片75 mg/次,1次/d。两组均连续治疗3个月。比较两组患者治疗前后的临床疗效,血压,血脂指标总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),颈动脉粥样硬化斑块面积和厚度,颈动脉粥样硬化斑块分级的变化。结果治疗后,治疗组的总有效率(93.3%)明显高于对照组(70.0%),两组比较差异有统计学意义(P0.05);治疗后,两组患者的收缩压和舒张压均较治疗前明显降低,差异具有统计学意义(P0.05);治疗组治疗后的收缩压和舒张压均较对照组治疗后显著降低,差异有统计学意义(P0.05);治疗后,两组的TC、TG、HDL-C、LDL-C均较治疗前显著改善,差异具有统计学意义(P0.05);治疗组治疗后的TC、TG、HDL-C、LDL-C均较对照组治疗后显著改善,差异具有统计学意义(P0.05);两组患者治疗后颈动脉粥样硬化斑块面积、厚度较治疗前均明显变小,差异有统计学意义(P0.05);治疗组治疗后的颈动脉粥样硬化斑块面积和厚度均较对照组治疗后显著改善,差异具有统计学意义(P0.05);治疗后,两组的颈动脉动脉粥样斑块均有改善,治疗前后比较差异具有统计学意义(P0.05);且治疗组治疗后颈动脉动脉粥样斑块较对照组治疗后有所改善,且差异具有统计学意义(P0.05)。结论氯吡格雷联合阿托伐他汀钙治疗高血压合并颈动脉粥样硬化具有较好的临床疗效,能够有效减轻动脉粥样硬化,改善血压血脂,并稳定粥样斑块。     

Impact of adjunctive thiazolidinedione therapy on blood lipid levels and glycemic control in patients with type 2 diabetes

SUMMARY

Objective: This study was undertaken to assess the effect of pioglitazone hydrochloride and rosiglitazone maleate on blood lipid levels and glycemic control when these drugs are used as adjunctive therapy in type 2 diabetes.

Research design and methods: Patients with type 2 diabetes receiving metformin and/or sulfonylurea (n?=?829) were evaluated in this national, multicenter, retrospective study. Medical records from 318 endocrinology practices in the USA were randomly selected and screened for study inclusion. Data related to patient demographics and laboratory data were extracted from medical records and analyzed for primary and secondary outcomes.

Main outcome measures: The primary study outcome was the mean change in plasma triglyceride (TG) levels. Secondary outcome measures included mean changes in total cholesterol (TChol), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations and hemoglobin A1C levels.

Results:With pioglitazone, TG levels declined by a mean of 51.5?mg/dl (P?<?0.001), HDL-C levels rose by 3.3?mg/dl (P?<?0.001), and no change was seen in LDL-C or TChol. Treatment with rosiglitazone was associated with no significant change in TG levels and a 1.5?mg/dl mean increase in HDL-C (P?<?0.001). Furthermore, rosiglitazone therapy was associated with an 8?mg/dl mean increase in TChol (P?<?0.001), and a 5.8?mg/dl mean increase in LDL-C (P?<?0.001). Hemoglobin A1C levels were significantly reduced by approximately 1% within thiazolidinedione (TZD) cohorts (P?<?0.001), but were not significantly different between study groups (P?=?0.257).

Conclusions: Results from this study suggest that pioglitazone has a more favorable effect on lipid profiles of patients with type 2 diabetes compared with rosiglitazone. In particular, differences were observed in TG and LDL-C levels. Both TZDs were equivalent at reducing hemoglobin A1C levels. These differences in lipid effects may have an impact on cardiovascular outcomes. The full clinical importance of these lipid alterations must be further assessed in prospective trials.     

Efficacy and Safety of Rosuvastatin and Fenofibric Acid Combination Therapy versus Simvastatin Monotherapy in Patients with Hypercholesterolemia and Hypertriglyceridemia

Objectives

To evaluate the efficacy and safety of fixed-dose combinations of rosuvastatin and fenofibric acid (rosuvastatin/fenofibric acid) compared with simvastatin in patients with high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG).

Background

Combination therapy with a statin and a fibrate is one of the treatment options to manage multiple lipid abnormalities in patients with hypercholesterolemia and elevated TGs.

Methods

In this randomized, double-blind study, patients (n=474) with LDL-C ≥160 mg/dL and ≤240 mg/dL and TG ≥150 mg/dL and <400 mg/dL were treated for 8 weeks with simvastatin 40 mg, rosuvastatin/fenofibric acid 5 mg/135 mg, rosuvastatin/fenofibric acid 10 mg/135 mg, or rosuvastatin/fenofibric acid 20 mg/135 mg. Primary and secondary variables were mean percent changes in LDL-C comparing rosuvastatin/fenofibric acid 20 mg/135 mg with simvastatin 40 mg and rosuvastatin/fenofibric acid 10 mg/135 mg and rosuvastatin/fenofibric acid 5 mg/135 mg with simvastatin 40 mg, respectively. Additional efficacy variables included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (Apo) B, HDL-C, TG, and high-sensitivity C-reactive protein (hsCRP). Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests.

Results

Significantly greater reductions in LDL-C levels from baseline values were observed with the combination of rosuvastatin/fenofibric acid 20 mg/135 mg (?47.2%, p < 0.001), rosuvastatin/fenofibric acid 10 mg/135 mg (?46.0%, p < 0.001), and rosuvastatin/fenofibric acid 5 mg/135 mg (?38.9%, p = 0.007) than with simvastatin 40 mg (?32.8%). Significant (p ≤ 0.04 for all comparisons) improvements in non-HDL-C, ApoB, HDL-C, TG, and hsCRP levels were also observed with each of the rosuvastatin/fenofibric acid doses as compared with simvastatin 40 mg. Treatment-related AEs and discontinuations due to AEs were similar across groups. The incidence of serious AEs was 0% with simvastatin 40 mg, 3.4% with rosuvastatin/fenofibric acid 5 mg/135 mg, 0.8% with rosuvastatin/fenofibric acid 10 mg/135 mg, and 2.5% with rosuvastatin/fenofibric acid 20 mg/135 mg. No cases of rhabdomyolysis or drug-related myopathy were reported.

Conclusion

In patients with high LDL-C and TG levels, combination treatment with rosuvastatin/fenofibric acid was well tolerated, and each of the rosuvastatin/fenofibric acid doses produced greater reductions in LDL-C and improvements in other efficacy parameters, compared with simvastatin 40 mg.     

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis

ABSTRACT

Background: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals.

Objective: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL‐C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice.

Results: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10?mg achieved the 2003 European LDL‐C goals compared with those who received atorvastatin 10?mg or simvastatin 20?mg (?p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10?mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10?mg (?p < 0.001).

Conclusions: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL‐C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.     

Pharmacodynamic interaction between ezetimibe and rosuvastatin

SUMMARY

Background: Ezetimibe is a lipid-lowering drug indicated for the treatment of hypercholesterolemia as co-administration with HMG-CoA reductase inhibitors (statins) or as monotherapy. The primary objectives of this study were to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and the new statin rosuvastatin. A secondary objective was to examine the potential for a pharmacokinetic interaction between ezetimibe and rosuvastatin.

Methods: This was a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study in healthy hypercholesterolemic subjects (untreated low-density lipoprotein cholesterol [LDL-C] ≥ 130?mg/dL [3.37?mmol/L]). After the outpatient screening and NCEP Step I diet stabilization periods, 40 subjects were randomized to one of the 4 following treatments: rosuvastatin 10?mg plus ezetimibe 10?mg (n = 12); rosuvastatin 10?mg plus placebo (matching ezetimibe 10?mg) (n = 12); ezetimibe 10?mg plus placebo (matching ezetimibe 10?mg) (n = 8); or placebo (2 tablets, matching ezetimibe 10?mg) (n = 8). All study treatments were administered once daily in the morning for 14 days as part of a 16-day inpatient confinement period. Fasting serum lipids were assessed pre-dose on days 1 (baseline), 7, and 14 by direct quantitative assay methods. Safety was evaluated by monitoring laboratory tests and recording adverse events. Blood samples were collected for ezetimibe and rosuvastatin pharmacokinetic evaluation prior to the first and last dose and at frequent intervals after the last dose (day 14) of study treatment. Plasma ezetimibe, total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and rosuvastatin concentrations were determined by validated liquid chromatography with tandem mass spectrometric detection (LC–MS/MS) assay methods.

Results: All active treatments caused statistically significant (?p ≤ 0.02) decreases in LDL-C concentration versus placebo from baseline to day 14. The co-administration of ezetimibe and rosuvastatin caused a significantly (?p < 0.01) greater reduction in LDL-C and total cholesterol than either drug alone. In this 2-week inpatient study with restricted physical activity there was no apparent effect of any treatment on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The co-administration of ezetimibe and rosuvastatin caused a significantly (?p < 0.01) greater percentage reduction in mean LDL-C (–61.4%) than rosuvastatin alone (–44.9%), with a mean incremental reduction of –16.4% (95%CI –26.3 to –6.53). Reported side effects were generally mild, nonspecific, and similar among treatment groups. There were no significant increases or changes in clinical laboratory tests, particularly those assessing muscle and liver function. There was no significant pharmacokinetic drug interaction between ezetimibe and rosuvastatin.

Conclusions: Co-administration of ezetimibe 10?mg with rosuvastatin 10?mg daily caused a significant incremental reduction in LDL-C compared with rosuvastatin alone. Moreover, co-administering ezetimibe and rosuvastatin was well tolerated in patients with hypercholesterolemia.     

Efficacy and safety of extended-release fluvastatin in Turkish patients with hypercholesterol­aemia: TULiPS (Turkish Lipid Study)

ABSTRACT

Objective: The efficacy and safety of extended-release fluvastatin (fluvastatin XL), 80?mg once daily, was assessed in Turkish patients with primary hypercholesterolaemia (low-density lipoprotein cholesterol (LDL?C) 3.37–5.70?mmol/l and triglyceride (TG) <?4.52?mmol/l).

Research design: in this open-label, prospective, multi-centre study, 154 patients were given fluvastatin XL 80?mg once daily and lipid levels were assessed after 2 and 12 weeks.

Results: Fluvastatin XL 80?mg once daily significantly reduced LDL?C levels by 38.8 and 38.1% at weeks 2 (n = 140) and 12 (n = 116), respectively (?p < 0.001 vs. baseline). Treatment with fluvastatin XL for 2 and 12 weeks significantly reduced total cholesterol levels by 30.2 and 27.4%, respectively (?p < 0.001 vs. baseline) and reduced TG levels by 14.9 and 7.5%, respectively (?p < 0.001 vs. baseline). Following stratification by risk factors for coronary heart disease (CHD) according to the National Cholesterol Education Program Adult Treatment Panel iii guidelines, 87.3% of patients with ≥?2 risk factors, and 67.4% of patients with existing CHD or CHD risk equivalents achieved target LDL?C levels (<?3.37?mmol/l and <?2.59?mmol/l, respectively) with fluvastatin XL. Fluvastatin XL reduced high-density lipoprotein cholesterol by 8.9 and 4.7% at weeks 2 and 12 weeks, respectively. fluvastatin XL 80?mg once daily was generally well-tolerated.

Conclusions: This open-label study indicates fluvastatin XL 80?mg once daily is an effective and well-tolerated lipid-lowering therapy for the reduction of CHD risk in Turkish patients.     

Atorvastatin affects C-reactive protein levels in patients with coronary artery disease

SUMMARY

Background: Elevated levels of C-reactive protein (CRP) are considered to be one of the indicators of poor prognosis in coronary artery disease (CAD). The aim of this study was to evaluate anti-inflammatory effects of atorvastatin in patients with CAD by measuring serum CRP levels.

Methods: After measuring the baseline levels of CRP and lipid fractions, the patients were divided into two groups. In Group A (n?=?46), atorvastatin (20?mg/day) was administered in addition to classic antianginal treatment (beta-blocker, nitrate and aspirin). In Group B (n?=?32), the usual antianginal treatment was continued. Following 4 weeks of treatment the same measurements were repeated.

Results: In Group A, CRP decreased from 20.3?mg/dl (95% CI, 9-31.8) to 10.8?mg/dl (95% CI, 2.7-18.9) (p?<?0.001). In Group B, CRP decreased from 17?mg/dl (95% CI, 13.1-21) to 12.8?mg/dl (95% CI, 9.7-15.9) (p?<?0.01). The decrease in group A was more than in group B (p?=?0.003).

Conclusions: In patients with CAD, atorvastatin exerted an anti-inflammatory effect represented by decreasing CRP levels. This effect was independent of the change in low density lipoprotein cholesterol (LDL-C) or high density lipoprotein cholesterol (HDL-C) levels.     

Effect of rimonabant,micronised fenofibrate and their combination on cardiometabolic risk factors in overweight/obese patients: a pilot study

Objective: To assess the effect of rimonabant, micronised fenofibrate and their combination on anthropometric and metabolic parameters in overweight/obese patients with dyslipidaemia. Methods: All patients (n = 30) received a hypocaloric diet (～ 600 kcal/day deficit) and were randomly allocated to receive open-label rimonabant (R) 20 mg/day (n = 10), micronised fenofibrate (F) 200 mg/day (n = 10) or rimonabant 20 mg/day plus fenofibrate 200 mg/day (RF) (n = 10). Anthropometric and metabolic parameters were assessed at baseline and 3 months after treatment initiation. Results: Compared with baseline similar significant reductions in body weight, body mass index and waist circumference were observed in the R (–6, –5 and –5%, respectively; p < 0.01) and RF group (–5% for all, p < 0.05), while improvements in these parameters were smaller in the F group (–2, –2.5 and –2%, respectively; p < 0.05). Triglycerides were reduced by 18% in the R group (p = NS), by 39% in the F group (p < 0.001) and by 46% in the RF group (p < 0.05). Importantly, combination treatment resulted in a 42% increase in high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05), while HDL-C was not significantly altered in the two monotherapy groups. Subsequently, a more pronounced increase in apolipoprotein A-I (ApoA-I) levels (+25%) was observed in the RF group compared with changes in both monotherapy groups (p < 0.0001 vs R and p < 0.005 vs F group). Low-density lipoprotein cholesterol (LDL-C) levels were not significantly altered in any group. Apolipoprotein B (apoB) levels were reduced in all groups and this reduction was significantly more pronounced in the RF group (p < 0.05 vs baseline as well as p < 0.005 and p < 0.01 for RF vs R and F groups, respectively). ApoB/apoA-I ratio decreased by 3% with R (p = NS), by 18% with F (p < 0.05) and by 40% with RF treatment (p < 0.01). Total cholesterol to HDL-C ratio decreased by 20% with F (p < 0.0001) and by 33% with RF therapy (p < 0.005), while it was not significantly altered in R group. Conclusion: The combination of rimonabant and fenofibrate may further improve metabolic parameters in overweight/obese patients with dyslipidaemia compared with each monotherapy. This improvement is particularly pronounced for HDL-C levels.     

Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy

OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial. METHODS: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5 mg, 10 mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12. RESULTS: Rosuvastatin 5 mg and 10 mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5 mg and 10 mg, respectively, vs. -0.5% for placebo; p < 0.001), as did Apo A-I levels (p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported. CONCLUSIONS: Rosuvastatin 5 mg or 10 mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.