Effects of switching statins on achievement of lipid goals: measuring effective reductions in cholesterol using rosuvastatin therapy (MERCURY I) study

Background

In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients.

Methods

Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis.

Results

Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P < .05), simvastatin 20 mg (86% vs 72%, P < .0001), and pravastatin 40 mg (88% vs 66%, P < .0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P < .01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks.

Conclusions

We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

The achievement of target cholesterol level differs between coronary heart disease and diabetic patients

Background

Guidelines recommend that LDL-C level should be < 100 mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

Objective

To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

Methods

The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n = 54,261), CHD (n = 24,083) or DM and CHD (n = 15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level < 100 mg/dl and its association with demographic and clinical parameters were analyzed.

Results

The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p < 0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C > 7% or missing its measurements had a negative predictive value.

Conclusions

The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.     

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.     

Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST-elevation acute coronary syndromes treated with dalteparin: a GUSTO IV substudy

Background

In acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity.

Methods

The Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST-elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours.

Results

The median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4-7.8 ng/L, P <.001; 4.4-8.7 mg/L, P <.001; 3.3-3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups.

Conclusions

In non-ST-elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.     

Comparison of the effect of simvastatin versus simvastatin/ezetimibe versus rosuvastatin on markers of inflammation and oxidative stress in subjects with hypercholesterolemia

Objectives

Statins may exhibit anti-inflammatory and antioxidant effects. Whether different statins at equivalent doses or the combination of low-dose statin with ezetimibe have comparable anti-inflammatory and antioxidant effects is unknown. The aim of this study was to compare the effects of simvastatin, simvastatin/ezetimibe or rosuvastatin at equivalent low-density lipoprotein cholesterol lowering doses on inflammation and oxidative stress indices in subjects with hypercholesterolemia.

Methods

This was a pre-specified analysis of a prospective, randomized, open-label, blinded endpoint (PROBE) study. We enrolled one hundred and fifty three (n = 153) hypercholesterolemic subjects who were randomized to receive simvastatin 40 mg or simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg daily. Plasma 8-Epi prostaglandin F2 alpha (8-epiPGF2a), oxidized LDL (oxLDL) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity and mass were measured at baseline and following 12 weeks of treatment.

Results

A significant reduction in plasma 8-isoprostane and oxLDL levels was observed in all treatment groups [by 10%, 8% and 6% (p < 0.05 compared with baseline) and 41%, 40% and 39% (p < 0.001 compared with baseline) in simvastatin, simvastatin/ezetimibe and rosuvastatin groups, respectively]. In all treatment groups a significant reduction in total plasma Lp-PLA₂ activity and mass was observed (by 36%, 31% and 38% and 36%, 32% and 32% for simvastatin, simvastatin/ezetimibe and rosuvastatin, respectively, p < 0.001 compared with baseline). No intergroup differences were observed.

Conclusions

Simvastatin 40 mg, simvastatin/ezetimibe 10/10 mg and rosuvastatin 10 mg significantly reduced 8-epiPGF2a, oxLDL and Lp-PLA₂ activity and mass to a similar extent.     

Safety and effectiveness of the association ezetimibe-statin (E-S) versus high dose rosuvastatin after acute coronary syndrome: The SAFE-ES study

Background

Statin therapy is a cornerstone therapy for secondary prevention after acute coronary syndrome (ACS). However, the use of these drugs can be limited by side effects, mainly muscular pain. Ezetimibe is a newer lipid-lowering agent, with fewer side effects.

Aims

The present study was designed to compare a commercially available association of ezetimibe and simvastatin (E-S) to high dose Rosuvastatin on cholesterol and muscular enzyme levels and occurrence of muscular pain.

Methods

All consecutive ACS statin-naïve patients with LDL cholesterol (LDL-C) > 100 mg/dL randomly received either high dose statin (Rosuvastatin 20 mg) or E-S 10/40-mg. All patients had one-month follow-up with biological testing and clinical examination. We compared the two groups on the biological efficiency and incidence of muscular pain.

Results

One hundred and twenty-eight patients were randomized; 64 received E-S and 64 Rosuvastatin. In the two groups, the lowering of LDL-C level (Δ = 51%) at one month was significant (P < 0.01) without any difference in the rate of lowering on LDL-C or HDL-C suggesting that E-S is as effective as high dose Rosuvastatin (P = 0.77 and P = 0.99). The rate of patients reaching the objective of LDL-C < 100 mg/dL (45%) and LDL-C < 70 mg/dL (51%) was not different in the two clusters (P = 0.65). Incidence of muscular pain was 15% higher in patients treated with Rosuvastatin (P = 0.01) without any difference on CPK level (P = 0.6).

Conclusion

Using an association of E-S in an effective alternative strategy to high dose Rosuvastatin with a lower incidence of muscular pain, which might impact adherence to medication after ACS.     

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention

Background

Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain.

Methods

The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG ≥126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 ± 1.2 years.

Results

The average patient age was 62 ± 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM , 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P = .04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG ≥109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P = .002) remained independent predictors of mortality.

Conclusions

Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.     

Use of a treatment optimization algorithm involving statin-ezetimibe combination aids in achievement of guideline-based low-density lipoprotein targets in patients with dyslipidemia at high vascular risk Guideline-based Undertaking to Improve Dyslipidemia Management in Canada (GUIDANC)

Background

Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease.

Methods and Results

In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits (P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement.

Conclusions

Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management.     

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.     

Impact of statin therapy on LDL and non-HDL cholesterol levels in subjects with heterozygous familial hypercholesterolaemia

Background and aimsCardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins.Methods and resultsAmong primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included.LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects.ConclusionAccording to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.     

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.     

Cost of care distribution in atrial fibrillation patients: the COCAF study

Background

Atrial fibrillation (AF) currently represents a major economic burden for society. Very few studies have been performed to evaluate the cost of care for AF patients. This study is a large prospective survey designed to analyze the different cost drivers in the treatment of these patients. This survey, named Cost of Care in Atrial Fibrillation (COCAF), evaluated the cost of care for patients with AF treated by cardiologists in general office practice.

Methods

A group of 671 patients was recruited by 82 cardiologists distributed in all regions of France. The mean age of the patients was 69 years, and 64% were male. The mean follow-up was 329 ± 120 days. The costs of care were analyzed from the health care payer and the societal perspectives.

Results

During the follow-up period, 21 patients (3.13%) died and 210 (31.3%) patients were hospitalized. The number of hospitalizations and deaths was significantly higher in the group of persistent or permanent AF (PEAF) patients, as compared to paroxysmal AF (PAAF) patients. Hospitalizations were much more frequent in the PEAF group (127) than in the PAAF group (83, P < .05). Deaths were also much more frequent in the PEAF group (17) as compared to the PAAF group (4, P < .001). From the societal perspective, the first cost driver was hospitalizations (52%), followed by drugs (23%), consultations (9%), further investigations (8%), loss of work (6%), and paramedical procedures (2%). In multivariate analysis the following parameters were significantly associated with higher costs: heart failure (P < .04), coronary artery disease (P < .001), use of class III antiarrhythmic drugs (P < .002), hypertension (P < .002) and metabolic disease (P < .001).

Conclusions

This prospective survey shows that hospitalizations represent the major cost driver in the treatment of AF patients. Outpatient care programs must be proposed to AF patients in order to avoid readmissions and to reduce the cost of treatment.