Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II

Background

National Cholestesrol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of <100 mg/dL. This target can be difficult to attain with diet and current therapy.

Methods

In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks.

Results

At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of <70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides ≥200 mg/dL) met LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity.

Conclusion

Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.     

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial

Background

This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease.

Methods

After a 6-week dietary lead-in period, patients with LDL-C levels ≥160 and <250 mg/dL and triglyceride levels ≤400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128).

Results

At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P < .001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P < .01], 47% [P < .001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P < .01], 59% [P < .001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P < .01). Effects of the 2 agents on triglycerides were similar.

Conclusions

Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.     

More Western hypercholesterolemic patients achieve Japan Atherosclerosis Society LDL-C goals with rosuvastatin therapy than with atorvastatin, pravastatin, or simvastatin therapy.

BACKGROUND: Data from Western comparative trials suggest that rosuvastatin is more effective than atorvastatin, simvastatin, and pravastatin in helping hypercholesterolemic patients achieve US and European lipid-lowering guidelines. The purpose of this analysis was to assess the comparative efficacy of rosuvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to levels recommended by the Japan Atherosclerosis Society (JAS). METHODS AND RESULTS: A post hoc analysis of data from 6 randomized, double-blind, active-controlled trials was conducted to evaluate the relative efficacy of rosuvastatin and comparator statins in helping patients achieve the LDL-C goals established by the JAS. The first 5 trials, prospectively designed for pooling, were originally conducted to compare the effects of rosuvastatin with either atorvastatin, simvastatin, or pravastatin in reducing lipid levels and helping patients achieve the LDL-C goals established by the National Cholesterol Education Program. The 6th trial was conducted with similar objectives, but in patients with heterozygous familial hypercholesterolemia (HeFH). Data from 2,139 hypercholesterolemic patients in the first 5 trials were pooled for analysis: rosuvastatin 5 mg (n=390) or 10 mg (n=389) vs atorvastatin 10 mg (n=393); rosuvastatin 5 mg (n=240) or 10 mg (n=226) vs simvastatin 20 mg (n=249) or pravastatin 20 mg (n=252). In the studies with atorvastatin as the comparator, JAS-defined LDL-C goals were reached by 67.2% of the rosuvastatin 5-mg group, 82.3% of the rosuvastatin 10-mg group, and 58.0% of the atorvastatin 10-mg group (p<0.001 for both rosuvastatin groups vs atorvastatin) at 12 weeks. Similarly, in the trials with pravastatin and simvastatin as comparators, the JAS LDL-C goals were reached by 77.5% of the rosuvastatin 5-mg group, 86.7% of the rosuvastatin 10-mg group, 45.2% of the pravastatin 20-mg group and 65.5% of the simvastatin 20-mg group (p<0.001 for both rosuvastatin groups vs pravastatin and simvastatin). In the trial of HeFH patients (n=433 for rosuvastatin, n=187 for atorvastatin), 31.9% of patients treated with rosuvastatin 20 mg achieved JAS LDL-C goals, compared with 17.6% of patients treated with atorvastatin 20 mg (p<0.001). CONCLUSIONS: Rosuvastatin has demonstrated clinical superiority over atorvastatin, pravastatin, and simvastatin in reducing LDL-C levels and in enabling patients to reach goals established by the JAS.     

Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial

AIM: The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. METHODS: The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. RESULTS: LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. CONCLUSIONS: Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS.     

Comparison of the efficacy and safety of rosuvastatin versus atorvastatin,simvastatin, and pravastatin across doses (STELLAR* Trial)

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.     

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.     

Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome

The metabolic syndrome (MS) is a constellation of coronary risk factors. Atherogenic dyslipidemia is an important factor in cardiovascular risk in these patients, and treatment of atherogenic dyslipidemia has been identified as an important goal of therapy in patients with MS. This post hoc analysis of data from a 6-week, randomized, open-label, parallel-group, comparative trial (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin [STELLAR]) assessed the effects of rosuvastatin 10, 20, and 40 mg, atorvastatin 10, 20, 40, and 80 mg, simvastatin 10, 20, 40, and 80 mg, and pravastatin 10, 20, and 40 mg on plasma lipids in hypercholesterolemic patients (low-density lipoprotein cholesterol >/=160 and <250 mg/dl; triglycerides <400 mg/dl) who had >/=3 of the 5 National Cholesterol Education Program Adult Treatment Panel III criteria for MS (body mass index >30 kg/m(2) substituted for waist circumference). Of 2,268 patients, 811 met criteria for MS. Percent reductions in low-density lipoprotein cholesterol ranged from 20% in the pravastatin 10-mg group to 55% in the rosuvastatin 40-mg group. In patients with MS, triglyceride reductions were 22% to 34% with rosuvastatin, 23% to 33% with atorvastatin, 15% to 23% with simvastatin, and 12% to 15% with pravastatin. High-density lipoprotein cholesterol increased by 8% to 11% with rosuvastatin, 5% to 9% with atorvastatin, 8% to 10% with simvastatin, and 3% to 7% with pravastatin. Rosuvastatin, atorvastatin, simvastatin, and pravastatin treatment had favorable effects in hypercholesterolemic patients on the atherogenic dyslipidemia associated with MS. Rosuvastatin had the most favorable effect on the atherogenic lipid profile of MS overall.     

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.     

Effects of switching statins on lipid and apolipoprotein ratios in the MERCURY I study

BACKGROUND: Lipid ratios are clinically useful markers of coronary artery disease (CAD) risk. The effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on lipid ratios were investigated in the Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY (MERCURY) I trial. METHODS: This trial was conducted in 3140 hypercholesterolemic patients with CAD, atherosclerosis, type 2 diabetes mellitus, or a 20% 10-year risk for CAD. Patients were randomized to rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks; all patients except those receiving rosuvastatin 10 mg either were switched to rosuvastatin 10 or 20 mg or remained on initial treatment for 8 more weeks. RESULTS: At 8 weeks, reductions in total cholesterol (TC):high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol:HDL-C, non-HDL-C:HDL-C, and apolipoprotein (apo) B:apo A-I ratios with rosuvastatin 10 mg were significantly greater than those with atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, and pravastatin 40 mg (P<0.0001 for all). At week 16, switching to rosuvastatin 10 mg from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg and to rosuvastatin 20 mg from atorvastatin 20 mg produced significantly greater reductions in all lipid ratios (P< or =0.0001 for all). Switching to rosuvastatin 10 mg from atorvastatin 20 mg produced significantly greater reductions in TC:HDL-C (P<0.025) and apo B:apo A-I (P<0.01). CONCLUSIONS: Rosuvastatin 10 mg reduces lipid ratios more than equivalent and higher doses of other statins; switching to equal or lower doses of rosuvastatin produces significantly improved reductions in lipid ratios.     

Rosuvastatin is cost-effective in treating patients to low-density lipoprotein-cholesterol goals compared with atorvastatin, pravastatin and simvastatin: analysis of the STELLAR trial.

BACKGROUND: Rosuvastatin calcium (CRESTOR) has demonstrated superior efficacy in reducing low-density lipoprotein cholesterol (LDL-C). However, healthcare providers and authorities require information on its cost-effectiveness in the treatment of dyslipidaemia. DESIGN: A retrospective pharmacoeconomic analysis was performed using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. The cost-effectiveness of rosuvastatin 10-40 mg was compared with atorvastatin 10-80 mg, pravastatin 10-40 mg and both branded and generic simvastatin 10-80 mg in achieving Third Joint European Task Force LDL-C goals in patients with hypercholesterolaemia. METHODS: The analysis was conducted from the perspective of the UK National Health Service, using clinical data from the STELLAR trial and drug acquisition costs. Cost-effectiveness was compared using incremental cost-effectiveness ratios (ICERs), with sensitivity analyses applied to both efficacy and cost parameters. RESULTS: In terms of patients achieving goal, rosuvastatin 10 mg dominated (was more effective at equal or lower cost) atorvastatin 10 and 20 mg, pravastatin 20 and 40 mg, branded simvastatin 10-80 mg and generic simvastatin 40 and 80 mg. Where rosuvastatin 10 mg did not dominate, ICERs ranged from 36 pounds sterling to 162 pounds sterling per extra patient to goal. Rosuvastatin 20 and 40 mg were cost-effective compared with milligram-equivalent and higher doses of other branded statins. Sensitivity analyses showed that the results were robust to variations in both statin efficacy and price. CONCLUSION: In patients with hypercholesterolaemia, rosuvastatin is a cost-effective statin option in treating to LDL-C goals.     

The effects of atorvastatin and rosuvastatin on oxidative stress in diabetic patients

Aim

Diabetes is associated with abnormalities in lipid profile and increased oxidative stress. Statins are preferred agents in diabetic patients due to their antioxidant and LDL-C lowering effects. This study is designed to compare the effects of atorvastatin and rosuvastatin on low density lipoprotein cholesterol (LDL-C), lipid hydroperoxide (LOOH), total oxidant status (TOS) and total antioxidant capacity (TAC) in diabetic patients with hyperlipidemia.

Materials and methods

Sixty two patients who have type 2 diabetes mellitus with serum LDL levels more than 100 mg/dL were randomly assigned to receive atorvastatin 20 mg (n = 31) or rosuvastatin 10 mg (n = 31). Blood tests were performed at the beginning of the study and after three months.

Results

There were no statistically significant differences in the pre- and after treatment levels of the LDL-C between groups. TAC values were increased in both groups and statistically significant in the former group (p = 0.007). There was no diferrence between the change percentages ((after treatment TAC − pretreatment TAC) / pretreatment level) of TAC between two treatment groups. The effects of two drugs on the other oxidative parameters were not significantly different.

Conclusion

Both atorvastatin and rosuvastatin may be helpful in reducing increased oxidative stress in diabetic patients with hyperlipidemia.     

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.     

A comparative evaluation of safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia

AIM:

To evaluate and compare the safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia.

MATERIALS AND METHODS:

This open-label, randomized, parallel group, comparative, prospective study of 12-weeks duration included 60 patients of type-2 diabetes with dyslipidemia having good glycemic control with fixed dose combination of tablet glimepiride + metformin and divided into three groups of twenty each. Group-1 patients have received tablet rosuvastatin 10 mg once daily, group-2 received tablet atorvastatin 10 mg once daily, and group-3 received tablet simvastatin 10 mg once daily for 12 weeks each. The levels of serum cholesterol, serum triglyceride, LDL, VLDL, and HDL were assessed at baseline and at the end of 12 weeks.

RESULTS:

The mean serum cholesterol, serum triglyceride, LDLc, and VLDLc levels were significantly reduced on therapy (P<0.001). Simultaneously, the mean levels of HDL were highly significantly increased (P<0.001) after therapy for 12 weeks with rosuvastatin, atorvastatin, and simvastatin. Reduction of LDL levels in rosuvastatin group was statistically significant when compared with those of simvastatin group (P< 0.05) but was statistically nonsignificant when compared with atorvastatin group (P> 0.05). Conclusion: 10 mg of rosuvastatin was comparable to 10 mg of atorvastatin and more efficacious than 10 mg simvastatin in reducing LDL levels after 12 weeks of therapy in patients of type 2 diabetes mellitus with dyslipidemia.     

Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia

Background

Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease. In addition to fenofibrate, there is some evidence that atorvastatin may have a hypouricemic action, but the underlying mechanisms remain speculative.

Methods

This randomized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia. A total of 180 patients were enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or simvastatin. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained for creatinine, sodium, and uric acid determinations.

Results

Baseline serum uric acid levels correlated positively with the body mass index, serum insulin, creatinine, and triglyceride levels and inversely with serum HDL cholesterol levels. Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels. However, only atorvastatin reduced serum uric acid levels (from 5.6 ± 1.7 to 4.9 ± 1.5 mg/dL, P < .0001) by augmenting its urinary fractional excretion (from 10.4% ± 7.9% to 12.0% ± 7.4%, P < .01). In a multivariate logistic regression analysis, the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables, including lipid parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P = .008).

Conclusions

Atorvastatin (but not simvastatin) significantly lowered serum uric acid levels. This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia.     

Comparison of the dose-response relationships of 2 lipid-lowering agents: a Bayesian meta-analysis

Background

Comparing the dose-response of a new drug to that of a previously studied drug can aid in understanding their relative potencies. Two dose-finding studies addressed the effect of a new drug, rosuvastatin, on its ability to decrease low-density lipoprotein cholesterol (LDL-C) levels. One of these studies included 2 doses of atorvastatin, and substantial additional information is available in the literature about the effect of atorvastatin on LDL-C level lowering.

Methods

The 2 dose-finding studies of rosuvastatin considered otherwise healthy patients who had hypercholesterolemia. Comparable studies of atorvastatin were identified via a MEDLINE search in December 1999. Multiple reviewer consensus identified 15 of 41 studies on atorvastatin published since 1996 that met these selection criteria: reporting of LDL-C level change from baseline at least 6 weeks after treatment initiation, doses administered, and treatment group sizes. Eligible populations had clinical evidence of hypercholesterolemia. We excluded studies with patients who had severe illness or a previous history of transplantation. Data extraction of the mean, sample sizes, and SDs (or CIs) by dose was carried out independently by multiple reviewers. We combined the results from the various studies with Bayesian hierarchical modeling and analyzed them with Markov chain Monte Carlo techniques.

Results

Combining this study and literature results substantially increased the power to compare the dose-response relationships of rosuvastatin and atorvastatin. Rosuvastatin reduced LDL-C level by an estimated 10 to 17 percentage points more than atorvastatin when both were given at the same dose. Approximately one quarter of the dose of rosuvastatin achieved about the same magnitude of LDL-C level reduction as atorvastatin at dosages as high as 80 mg. This finding does not imply a 4-fold difference in efficacy overall and specifically does not describe the results at higher dosage levels.

Conclusions

Bayesian meta-analysis of results from related studies allows the comparison of the dose-response relationships of 2 drugs, better estimates of a particular dose-response relationship within an individual study, and the expression of relative benefits (of dose and drug) in terms of probabilities. Explicitly comparing a study’s results with historical data using Bayesian meta-analysis allows clinicians to view the study in the larger context of medical research.     

Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS)

Background

Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins.

Methods

A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome.

Results

Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs −0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs −1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, ≥40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3× the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin).

Conclusions

Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3× the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.     

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.     

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.     

Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease (from the IRIS Trial)

In a large randomized trial of statin therapy in patients of South-Asian origin with hypercholesterolemia, 740 patients in the United States and Canada received 6 weeks of treatment with rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg. A total of 485 patients (66%) were categorized as being at high risk of coronary heart disease and had a National Cholesterol Education Program Adult Treatment Panel III treatment goal of low-density lipoprotein (LDL) cholesterol <100 mg/dl (<2.6 mmol/L). LDL cholesterol decreased by 45% with rosuvastatin 10 mg versus 40% with atorvastatin 10 mg (p = 0.0023) and by 50% with rosuvastatin 20 mg versus 47% with atorvastatin 20 mg (p = NS). National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol goal achievement rates in high-risk patients (all patients) were 76% (79%) and 88% (89%) with rosuvastatin 10 and 20 mg, respectively, compared with 70% (76%) and 81% (85%) with atorvastatin 10 and 20 mg, respectively. Rosuvastatin and atorvastatin were well tolerated. There were no clinically relevant differences between statins in adverse events or incidence of creatine kinase >10 times the upper limit of normal, alanine aminotransferase >3 times the upper limit of normal on 2 consecutive occasions, or proteinuria or hematuria over the relatively short duration of treatment. In conclusion, statin therapy was well tolerated and effective in decreasing LDL cholesterol in patients of South-Asian origin, with the 10- and 20-mg doses of rosuvastatin and atorvastatin allowing most patients to reach recommended LDL cholesterol goals.     

Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction – A pilot study

Objective

Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI).

Methods

Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with ¹²³⁻I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and ²⁰¹⁻thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR−AAI) × 100/AAR (%)].

Results

Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (−37.6% ± 17.2%) and atorvastatin (−32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (−53.3% ± 48.8% versus −13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01).

Conclusion

Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with increasing CoQ10/LDL-C.Clinical trial registration: URL http://www.umin.ac.jp/ctr/index.htm Unique Identifier: UMIN000003893.