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.     

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.     

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.     

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.     

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.     

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 Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis

Purpose

We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins.

Methods

We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), while secondary outcomes included adverse events and adherence.

Results

Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included in the analysis. Pooled analysis revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence interval [CI] ?1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI ?0.23, 21.26, p = 0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes in term of change in TC (MD 12.45 mg/L, 95%CI 8.14, 16.76, p < 0.00001, and 15.80 mg/dL, 95%CI 5.66, 25.95, p = 0.002, respectively). For all outcomes, there was no statistically significant difference between alternate-day and daily regimens for both fluvastatin and pravastatin (p > 0.05). Both regimens of statins were generally well tolerated with good adherence.

Conclusions

Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG.

     

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.     

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.     

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.     

International noninterventional study of acarbose treatment in patients with type 2 diabetes mellitus

Aim

To obtain data on efficacy, safety and tolerability of acarbose monotherapy or combination therapy during daily-life treatment.

Methods

This prospective, non-controlled, observational study enrolled patients with type 2 diabetes, whose physician decided that acarbose treatment was appropriate, from China, Middle East, Indonesia, Morocco, Pakistan, Philippines, Poland and Taiwan. The observation period included an initial visit and up to three follow-up visits; an extension of 2 years was realized in Pakistan and Poland.

Results

Of 14,574 patients enrolled, 14,418 comprised the intent-to-treat population. At the initial visit, 74.1% of patients had been treated with a glucose-lowering agent. Fasting blood glucose was reduced from 175.2 mg/dL at the initial visit to 133.7 mg/dL at the last visit (mean of 11.3 weeks after initial visit; P < 0.0001). Mean 2-h postprandial blood glucose decreased from 244.7 mg/dL to 172.4 mg/dL (P < 0.0001). HbA1c reduced from 8.4% to 7.4% (P < 0.0001). Glycemic efficacy was maintained over the 2-year extension period. There were 432 adverse events in 293 patients (2.03%), mainly gastrointestinal. Physicians assessed efficacy as “very good”/“good” in 85.1% of patients, and were “very satisfied”/“satisfied” with acarbose therapy in 94.3% of cases.

Conclusion

Acarbose therapy was efficacious and well tolerated in daily life in patients with type 2 diabetes.     

Moderate alcohol consumption and safety of lovastatin and warfarin among men: the post-coronary artery bypass graft trial

Purpose

Although moderate drinking has been associated with lower mortality among patients with coronary heart disease, its safety among patients taking common cardiac medications is unknown.

Subjects and methods

We studied 1244 men enrolled in the Post-Coronary Artery Bypass Graft (CABG) Trial who had undergone previous coronary bypass surgery. Participants were randomly assigned to lovastatin in low (mean 4 mg) or high (mean 76 mg) doses and to low-dose warfarin (mean international normalized ratio [INR] 1.4, goal INR <2.0) or placebo in a factorial design. Participants underwent routine measurement of alanine aminotransferase (ALT) and INR levels every 6 to 12 weeks for 4 to 5 years. We categorized weekly alcohol intake as abstention (<1 drink), light (1-6 drinks), moderate (7-13 drinks), and heavier (≥14 drinks).

Results

During follow-up, 66% of men taking warfarin had an INR of 2.0 or higher, and 7% of men had an ALT of 80 IU/L or higher. Maximum INR (P = .72) and ALT (P = .51) levels did not differ across categories of alcohol intake. The risks of an INR of 2.0 or higher were 67%, 66%, 68%, and 61% among non-, light, moderate, and heavier drinkers (P = .86), respectively. The corresponding risks of an ALT of 80 IU/L or more were 8%, 10%, 9%, and 6% (P = .70), respectively.

Conclusion

Moderate drinking did not adversely influence the safety of low-dose warfarin or even high-dose lovastatin among men in this randomized trial, as measured by INR and ALT levels.     

Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week,double-blind,randomized Phase 3 trial

Background

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.

Methods

In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events ≥ 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.

Results

Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001). At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients, respectively).

Conclusions

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.     

Lipoprotein (a) and venous thromboembolism in adults: a meta-analysis

Background

Lipoprotein (a) [Lp(a)], a low-density lipoprotein particle linked to apolipoprotein (a), has been recently demonstrated to be an independent risk factor for arterial vascular diseases. However, despite increasing evidence of the association between high Lp(a) and arterial thrombotic diseases, few and conflicting results on the association between high Lp(a) levels and venous thromboembolism have been obtained. The aim of this article is to systematically examine the published data on the association between high Lp(a) levels and venous thromboembolism.

Methods

A systematic search of all publications listed in the electronic databases (Medline, EMBASE, Web of Science, and The Cochrane Library) up to November 2006, using keywords in combination both as MeSH terms and text words, was conducted.

Results

Six case-control studies were included, incorporating 1826 cases of venous thromboembolism and 1074 controls. The summary odds ratios of included case-control studies under a fixed-effects model showed a statistically significant association between Lp(a) levels >300 mg/L and venous thromboembolism: 1.87, 95% confidence interval (CI), 1.51-2.30; P <.0001. Furthermore, a random-effects model, which accounts for the interstudy variation, yielded a similar estimate of increased risk (odds ratio [OR] 1.77; 95% CI, 1.14-2.75; P = .01).

Conclusions

The present meta-analysis shows a significant association between high Lp(a) levels and the occurrence of venous thromboembolism in adults. Indeed, the detection of Lp(a) could be of clinical relevance for venous thromboembolism, especially among patients with absence of traditional and thrombophilic risk factors.     

The Effect of a Hypertension Self-Management Intervention on Diabetes and Cholesterol Control

Background

Most patient chronic disease self-management interventions target single-disease outcomes. We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin (HbA_1c) and low-density lipoprotein cholesterol (LDL-C).

Methods

We evaluated patients from the Veterans Study to Improve the Control of Hypertension, a 2-year randomized controlled trial. Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care. Although the study focused on hypertension self-management, we compared changes in HbA_1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period. Changes in these laboratory values over time were compared between the 2 treatment groups using linear mixed-effects models.

Results

For the patients with diabetes, the hypertension self-management intervention resulted in a 0.46% reduction in HbA_1c over 2 years compared with usual care (95% confidence interval, 0.04%-0.89%; P = .03). For LDL-C, there was a minimal 0.9 mg/dL between-group difference that was not statistically significant (95% confidence interval, −7.3-5.6 mg/dL; P = .79).

Conclusions

There was a significant effect of the self-management intervention on the unintended target of HbA_1c,but not LDL-C. Chronic disease self-management interventions might have “spill-over” effects on patients' comorbid chronic conditions.     

Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease

The lipid-lowering effects of rosuvastatin and atorvastatin were determined across their dose ranges in a 6-week, randomized, double-blind trial. Three hundred seventy-four hypercholesterolemic patients with fasting low-density lipoprotein (LDL) cholesterol > or =160 but <250 mg/dl (> or =4.14 but <6.47 mmol/L) and fasting triglycerides <400 mg/dl (<4.52 mmol/L) and without active arterial disease within 3 months of entry received once-daily rosuvastatin (5, 10, 20, 40, or 80 mg [n = 209]) or atorvastatin (10, 20, 40, or 80 mg [n = 165]). The percentage decrease in plasma LDL cholesterol versus dose was log-linear for each drug, ranging from -46.6% to -61.9% for rosuvastatin 10 and 80 mg, compared with -38.2% to -53.5% for atorvastatin 10 and 80 mg. The dose curve for rosuvastatin yielded an 8.4% greater decrease in LDL cholesterol compared with atorvastatin at any given dose (p <0.001). Similarly greater decreases were observed for rosuvastatin across the dose range in total cholesterol (-4.9%), non-high-density lipoprotein (non-HDL) cholesterol (-7.0%), apolipoprotein B (-6.3%), and related ratios versus atorvastatin (all p <0.001). Because dose responses for HDL cholesterol, triglycerides, and apolipoprotein A-I were non-log-linear and nonparallel between the 2 drugs, percentage changes from baseline were compared at each dose. Significantly greater increases for rosuvastatin compared with atorvastatin were observed for HDL cholesterol at 40 and 80 mg, and for apolipoprotein A-I at 80 mg. Significantly greater triglyceride decreases were seen at 80 mg with atorvastatin over rosuvastatin. Both rosuvastatin and atorvastatin were well tolerated over 6 weeks.     

Efficacy and Safety of Rosuvastatin 5 mg in Combination with Fenofibric Acid 135 mg in Patients with Mixed Dyslipidemia – A Phase 3 Study

Background

Patients with mixed dyslipidemia characterized by elevated low-density lipoprotein cholesterol (LDL-C), elevated triglycerides (TG), and reduced high-density lipoprotein cholesterol (HDL-C) often require combination therapy to improve multiple lipid and nonlipid parameters. This phase 3, multicenter, randomized, double-blind study evaluated the efficacy and safety of rosuvastatin 5 mg coadministered with fenofibric acid 135 mg in patients with mixed dyslipidemia.

Methods

A total of 760 patients with TG?≥?150 mg/dL, HDL-C <40 mg/dL (<50 mg/dL for women), and LDL-C?≥?130 mg/dL were randomized for a 12-week treatment period to rosuvastatin 5 mg, fenofibric acid 135 mg, or rosuvastatin 5 mg + fenofibric acid 135 mg. The primary efficacy comparisons were mean percentage changes in HDL-C and TG (rosuvastatin + fenofibric acid vs. rosuvastatin monotherapy), and LDL-C (rosuvastatin + fenofibric acid vs. fenofibric acid monotherapy).

Results

Treatment with rosuvastatin + fenofibric acid resulted in statistically significant greater improvements in HDL-C (23.0% vs. 12.4%; P?P?P?Conclusion In conclusion, rosuvastatin 5 mg + fenofibric acid 135 mg resulted in comprehensive improvements in the lipid profile of patients with mixed dyslipidemia without unanticipated adverse events.