Achieving National Cholesterol Education Program Research Articles

Efficacy and safety of rosuvastatin versus atorvastatin in high-risk Chinese patients with hypercholesterolemia: a randomized, double-blind, active-controlled study

Objective: To evaluate and compare the efficacy and safety of rosuvastatin versus atorvastatin in a high-risk Chinese population with hypercholesterolemia.Research design and methods: This 6 week, prospective, multicenter, double-blind, three-arm, parallel-group, active-controlled study randomized adult Chinese patients (low-density lipoprotein cholesterol [LDL-C] ≥ 130–<250 mg/dL statin-naive and ≥100–<160 mg/dL in statin treated) to receive rosuvastatin (5 mg or 10 mg) or atorvastatin 10 mg. Patients not achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL-C targets in the randomized phase were administered rosuvastatin 10 mg and 20 mg in the open-label phase.Results: In total 414 patients (mean age: 59.5 ± 9.51 years, 59.4% females, mean LDL-C: 4.242 ± 0.676 mmol/L (rosuvastatin 5 mg), 4.13 ± 0.682 mmol/L (rosuvastatin 10 mg) and 4.213 ± 0.662 mmol/L (atorvastatin 10 mg) were analyzed. Compared with atorvastatin 10 mg, rosuvastatin 5 mg (−41.70% vs. −38.67%, p = .132) and rosuvastatin 10 mg showed greater LDL-C reduction (−46.28% vs. −38.67%, p = .0002). LDL-C target achievement rates with rosuvastatin 5 mg, rosuvastatin 10 mg and atorvastatin 10 mg were 61.0%, 79.1% and 58.3% in the randomized phase. In the open-label phase, LDL-C target achievement occurred in >40% with both doses of rosuvastatin. The rate of ≥1 adverse event was similar with rosuvastatin 5 mg (12.4%), 10 mg (11.7%) and atorvastatin 10 mg (8.9%).Conclusion: Rosuvastatin 5 mg demonstrated non-inferiority and rosuvastatin 10 mg demonstrated superiority to atorvastatin 10 mg for lowering LDL-C in high-risk Chinese patients with dyslipidemia, which was maintained through the open-label phase.Clinical trial registration: NCT00683618.

The Cost Effectiveness of Statin Therapies in Spain in 2010, after the Introduction of Generics and Reference Prices

HMG-CoA reductase inhibitors (statins) are the first-line drugs for use in the reduction of low-density lipoprotein cholesterol (LDL-C) levels and prevention of coronary heart disease (CHD) in patients with hypercholesterolemia. Generic statins could change the cost effectiveness of statin therapies in Spain, and more population groups could be included in the recommendations for reduction of cholesterol levels based on cost effectiveness. The objectives of this study were: (i) to assess the cost effectiveness of available statins for the reduction of LDL-C levels in Spain in 2010, after the introduction of generics and reference prices; (ii) to assess the cost effectiveness of combination therapy using a statin plus cholestyramine or ezetimibe; and (iii) to estimate the mean cost per patient to achieve National Cholesterol Education Program (Adult Treatment Panel-III) therapeutic objectives. The following treatments were evaluated: rosuvastatin 5-20 mg/day; atorvastatin, simvastatin, and pravastatin 10-40 mg/day; lovastatin and fluvastatin 20-80 mg/day; and combination therapy with a statin plus either cholestyramine 12-24 g/day or ezetimibe 10 mg/day. The cost effectiveness was evaluated in terms of cost per percentage point reduction in LDL-C, comparing the annual treatment costs with the effectiveness in reducing LDL-C. Treatment costs included those for medications (2010 wholesale prices), control measures, and treatment of adverse drug effects. The effectiveness of statins was estimated by developing a meta-analysis of clinical trials published between 1993 and 2005 that met several inclusion criteria. Average and incremental cost-effectiveness ratios were calculated to assess the efficiency of individual statin and combination therapies in reducing LDL-C levels. The effectiveness in terms of percentage reduction in LDL-C ranged from 19% for pravastatin 10 mg/day to 55% for atorvastatin 80 mg/day. Annual treatment costs ranged from Euro 189.7 for simvastatin 10 mg/day to Euro 759.3 for atorvastatin 80 mg/day. The cost-effectiveness ratios, in terms of cost per percentage point reduction in LDL-C, were: Euro 6 for simvastatin, Euro 10-12 for rosuvastatin, Euro 10 for lovastatin, Euro 13-16 for atorvastatin, Euro 13-14 for fluvastatin, and Euro 14-20 for pravastatin. Rosuvastatin + ezetimibe, simvastatin + ezetimibe, and atorvastatin + ezetimibe were the most cost-effective combination therapies for reducing LDL-C levels. Rosuvastatin was the most cost-effective statin for achieving the LDL-C therapeutic goal in patients at high risk for CHD, with a mean cost per patient of Euro 516. Simvastatin was the most cost-effective statin to achieve the LDL-C goal in patients with moderate or low CHD risk, with a cost per patient of Euro 217 and Euro 190, respectively. Rosuvastatin should be the first-choice agent in patients with high CHD risk, while simvastatin should be the first choice in patients with moderate or low risk. The addition of ezetimibe to rosuvastatin, simvastatin, or atorvastatin should be the preferred combination therapies when greater LDL-C reductions are required. The cost effectiveness of all statin therapies has increased in Spain after the introduction of generic statins and reference prices.

Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia

Aims: To demonstrate the equivalence of pitavastatin compared with the most commonly used doses of atorvastatin in the reduction of LDL-C in primary hypercholesterolemia or combined dyslipidemia. Secondary objectives included the comparison of pitavastatin against the most commonly used doses of atorvastatin in achieving National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and European Atherosclerosis Society (EAS) LDL-C goals, changes in other lipid parameters and safety. Method: An 18-to 20-week, prospective, randomized, double-blind,double-dummy, controlled trial assessing noninferiority of presumed equipotent doses of pitavastatin and atorvastatin in 821 patients with primary hypercholesterolemia or combined dyslipidemia. After a 6- to 8-week dietary lead-in period, randomized patients received one of four treatment regimens for 12 weeks. Two groups received pitavastatin (2 mg/day) or atorvastatin (10 mg/day) and two groups received pitavastatin (2 mg/day) or atorvastatin (10 mg/day) for 4 weeks followed by forced titration to pitavastatin (4 mg/day) or atorvastatin (20 mg/day). Results: The primary efficacy analysis showed pitavastatin was comparable to atorvastatin in percent change of LDL-C from baseline to endpoint (week 12 or last observation carried forward). The majority of patients achieved NCEP and EAS LDL-C goals at all doses, and more patients reached NCEP targets at the higher doses (pitavastatin: 78%; atorvastatin: 71%) than at the lower doses (pitavastatin: 57%; atorvastatin: 66%). There were some interesting differences between treatments in the other lipid parameters but none were statistically significant. Adverse event profiles were similar in all groups, with no apparent dose-related adverse events. Conclusion: Pitavastatin is equivalent to atorvastatin in reducing LDL-C in primary hypercholesterolemia or combined dyslipidemia, in both the lower-dose (pitavastatin 2 mgvs atorvastatin 10 mg) and higher-dose (pitavastatin 4 mg vs atorvastatin 20 mg) comparisons. Pitavastatin can be considered an effective, first-line therapy for these patients and offers an alternative, simple treatment regimen in the long-term care of primary hypercholesterolemia and combined dyslipidemia.

Benefits of the MEDPED treatment support program for patients with familial hypercholesterolemia

Patients with heterozygous familial hypercholesterolemia (FH) patients often have difficultly achieving National Cholesterol Education Program (NCEP) goals. Herein we present an evaluation of a centrally located, nationwide treatment support program that remotely attempted to educate and guide FH patients by monitoring their serum low-density lipoprotein (LDL) cholesterol levels and giving appropriate treatment recommendations through mail contact. All subjects were FH patients registered with the Make Early Diagnosis to Prevent Early Deaths (MEDPED) program. In this descriptive evaluation, we compared self-reported lipid levels in 386 FH patients participating in our treatment support program with 295 non-participants who had responded to questionnaires. Participants were recruited into the treatment support program if they had not reached their LDL cholesterol goal after at least 1 year of follow-up and were unable to receive specialized lipid care due to location. Participants who continued for a longer term in the treatment support program achieved greater total cholesterol reductions (14%) than the comparison group (7%, P=.004). Reductions in total and LDL cholesterol were highly correlated with more aggressive use of statin medications (P <.0001). These results demonstrate the potential benefits and limitations of a centralized program operating remotely to encourage appropriate treatment of severe hypercholesterolemia.

Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial

To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease (CAD). Prospective, multicentre, randomized, double-blind, placebo-controlled trial conducted in three Middle Eastern countries. Patients with known CAD, who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol (LDL-C) concentrations of 2.6 to 4.1 mmol/l, were randomized to receive daily coadministration of ezetimibe 10 mg or placebo. The primary outcome was percentage reduction of LDL-C after 6 weeks of randomization. Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C level and safety and tolerability. We enrolled 144 patients of whom 120 had blood available for final analysis. The coadministration of ezetimibe with ongoing simvastatin therapy resulted in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy (-26.7 versus -9.1%, respectively; total additional reduction of 17.6%, P < 0.0001). More patients in the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group (70 versus 33%, respectively; P = 0.0001). The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy. When coadministered with simvastatin therapy, ezetimibe resulted in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels. This was achieved safely and with excellent tolerability.

Effectiveness of a Fenofibrate 145‐mg Nanoparticle Tablet Formulation Compared with the Standard 160‐mg Tablet in Patients with Coronary Heart Disease and Dyslipidemia

To compare the effectiveness of a fenofibrate 145-mg nanoparticle tablet formulation with the standard 160-mg tablet in patients with dyslipidemia and coronary heart disease. Retrospective medical record review. Outpatient university-affiliated cardiology clinic. One hundred thirty patients with dyslipidemia and coronary heart disease treated for a minimum of 6 months with fenofibrate 160 mg/day (with or without 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor [statin] therapy) who were then switched to a minimum of 3 months of treatment with fenofibrate 145 mg/day. Low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride levels were compared during treatment with each formulation. In patients not taking statins, statistically significant reductions of 4.6% and 2.3%, respectively, were noted in mean triglyceride and LDL levels after the switch to fenofibrate 145 mg/day. In patients taking statins, statistically significant reductions of 5.1% and 2.8%, respectively, were observed in mean triglyceride and LDL levels. In total, a larger proportion of patients had 10% or greater improvement in LDL (14/130 [11%]) and triglyceride (32/130 [25%]) levels compared with the proportion of patients who had 10% or greater worsening in LDL (3/130 [2%]) and triglyceride (9/130 [7%]) levels, and a net additional 14 patients (11%) achieved National Cholesterol Education Program (NCEP) lipid panel targets after the switch to fenofibrate 145 mg/day. Mean HDL level was not significantly different after the switch to fenofibrate 145 mg/day. Safety parameters of fenofibrate 145-mg/day therapy were not examined, although fenofibrate 160 mg/day is generally well tolerated. Eleven percent of the patients in our study had improvements in their lipid profiles that resulted in achievement of NCEP lipid panel targets after treatment with the 145-mg nanoparticle formulation of fenofibrate. This improvement in lipid levels may have been related to increased bioavailability of the 145-mg formulation. However, the exact mechanism of the improvement in lipid levels is unknown.

Effects of fluvastatin extended-release (80 mg) alone and in combination with ezetimibe (10 mg) on low-density lipoprotein cholesterol and inflammatory parameters in patients with primary hypercholesterolemia: A 12-week, multicenter, randomized, open-label, parallel-group study

Background: Combining lipid-lowering agents with complementary mechanisms of action can provide greater cholesterol reductions than using either agent alone, improving achievement of target low-density lipoprotein cholesterol (LDL-C) levels. Objectives: The aim of this study was to assess the effects of fluvastatin extended-release (XL) 80 mg/d administered alone or combined with ezetimibe 10 mg/d on plasma lipid levels and inflammatory parameters in patients with primary hypercholesterolemia. The tol-erability of both regimens was also evaluated. Methods: In this multicenter, randomized, open-label, parallel-group study, patients with hypercholesterolemia were randomized in a 1:1 ratio to receive fluvastatin XL 80 mg/d alone or in combination with ezetimibe 10 mg/d for 12 weeks. The primary end point was the percentage change from baseline to week 12 in LDL-C level with fluvastatin XL + ezetimibe combination therapy compared with fluvastatin XL alone. Plasma concentrations of inflammatory biomarkers were measured at baseline and week 12. Proportions of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals were calculated. Tolerability was assessed by the monitoring and recording of all adverse events (AEs) and laboratory values. Results: A total of 82 patients were enrolled (mean [SD] age, 50.0 [12.0] years; 44% male; 100% white; mean [SD] weight, 73.5 [14.9] kg; combination group, 38 patients; monotherapy group, 44). Fluvastatin XL + ezetimibe and fluvastatin XL monotherapy were associated with significant decreases from baseline in mean LDL-C level (by 49.9% and 35.2%, respectively; between-group difference, P < 0.001). Fluvastatin XL + ezetimibe was associated with significantly greater reductions from baseline than fluvastatin XL monotherapy in total cholesterol (38.2% vs 27.5% P < 0.001), triglycerides (21% vs 3.8% P = 0.02) and apolipoprotein B (34.8% vs 22.5% P < 0.001). NCEP ATP III LDL-C goals were achieved by 87% of patients receiving fluvastatin XL + ezetimibe and 67% of patients receiving fluvastatin XL monotherapy (between-group difference, P = 0.042). The combination was associated with significantly lowered high-sensitivity C-reactive protein (hs-CRP) levels in patients with high baseline hs-CRP (>2 mg/L; P < 0.02), >1 cardiovascular risk factor (P < 0.05), or hypertension ( P = 0.015); both regimens were associated with significantly reduced plasma levels of interleukin-1B. No significant between-group differences in the incidences of AEs were found. Most AEs were mild or moderate in intensity. Headache was the most common AE, occurring in 5/44 (11.4%) patients in the fluvastatin XL group and 2/38 (5.3%) patients in the fluvastatin XL + ezetimibe group. One serious AE (convulsive crisis) occurred in a patient receiving fluvastatin XL + ezetimibe, but was not suspected to be related to study medication. Conclusion: Fluvastatin XL in combination with ezetimibe was found to be well-tolerated and effective, allowing the majority (87%) of these patients with primary hypercholesterolemia to achieve current treatment goals, and reduced hs-CRP levels in patients at higher cardiovascular risk.

Long-Term Efficacy and Safety of Rosuvastatin 40 mg in Patients With Severe Hypercholesterolemia

Patients with elevated low-density lipoprotein (LDL) cholesteral levels are at high risk of cardiovascular events but are often undertreated and fail to achieve lipid goals. This open-label, noncomparative, multicenter study assessed efficacy and safety of rosuvastatin 40 mg for < or =96 weeks in 1,380 patients with severe hypercholesterolemia, including heterozygous familial hypercholesterolemia. Patients > or =18 years old with fasting LDL cholesterol > or =190 and < or =260 mg/dl and triglycerides <400 mg/dl entered a 6-week dietary lead-in, before receiving rosuvastatin 40 mg for 48 weeks. An optional additional 48-week treatment period followed. The initial period had 2 primary end points: percentage of patients achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL cholesterol goals at 12 weeks, and long-term safety, assessed during 48 weeks by incidence and severity of adverse events (AEs) and abnormal laboratory values. Safety was the primary end point in the extension period. At 12 weeks, 83% of patients achieved NCEP ATP III LDL cholesterol goals, which were maintained during 48 and 96 weeks (81% and 84%, respectively). At 48 weeks, rosuvastatin 40 mg reduced LDL cholesterol from baseline by 52% and increased high-density lipoprotein (HDL) cholesterol by 11% (both p <0.0001). At 96 weeks, LDL cholesterol was reduced by 54% and HDL cholesterol increased by 13%. Rosuvastatin 40 mg was well tolerated during 96 weeks. The overall pattern and incidence of AEs and abnormal laboratory values were consistent with the published safety profile of rosuvastatin and higher doses of other statins. In conclusion, long-term treatment with rosuvastatin 40 mg is safe and effective in patients with severe hypercholesterolemia.

Efficacy and tolerability of fixed-dose combination of simvastatin plus ezetimibe in patients with primary hypercholesterolemia: Results of a multicentric trial from India

To compare the efficacy and safety of fixed-dose combination (FDC) of simvastatin and ezetimibe vs simvastatin monotherapy in Indian patients with primary hypercholesterolemia. This multicentric, double-blind, comparative, study conducted in India enrolled 230 patients with hypercholesterolemia (baseline low-density lipoprotein cholesterol [LDL-C] >120 mg/dL for patients on previous hypolipidemic drugs or >135 mg/dL for naïve subjects) were randomly assigned to receive either simvastatin (10 mg/day) or simvastatin (10 mg) plus ezetimibe (10 mg) FDC for 12 weeks. The primary efficacy endpoint was the mean percentage change in LDL-C from baseline to 12 weeks of therapy for simvastatin monotherapy vs simvastatin plus ezetimibe FDC. Secondary efficacy endpoints were mean percentage of changes in total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) from baseline to end of treatment, as well as proportion of patients achieving National Cholesterol Education Program Adult Treatment Panel III target LDL-C levels in each risk category. At the end of 12 weeks, the mean percentage reduction from baseline in LDL-C (-33.7%) was significantly greater with simvastatin and ezetimibe FDC compared to simvastatin alone (-26.28%, P < 0.05). Significantly greater percentage of patients (88%, P < 0.001) attained National Cholesterol Education Program Adult Treatment Panel III LDL-C target levels following ezetimibe/simvastatin treatment compared to simvastatin monotherapy (71%). Reductions in TG were significantly greater with ezetimibe/simvastatin than simvastatin (P < 0.001). Increases in HDL-C, and reduction in TC were similar between treatment groups. Safety and tolerability profiles were comparable for both treatments. Fixed-dose combination of simvastatin and ezetimibe provides a more effective means for reducing LDL cholesterol levels in Indian patients with hypercholesterolemia than simvastatin monotherapy without compromising the safety and tolerability profile.

Gender Differences in Adhering to National Guidelines in a Community Lipid Clinic

The aggressive treatment of hypercholesterolemia improves morbidity and mortality in patients with a history of cardiovascular disease irrespective of gender. Electronically tracked data on 4324 patients enrolled in a community lipid clinic were analyzed for gender differences in lipid values and adherence to national guidelines in lipid management. Women were older, more likely to be diabetic and/or hypertensive, and have a family history of coronary heart disease. Women also had higher initial total cholesterol, low-density lipoprotein, and triglyceride levels and were more likely to be at goal at entry for high-density lipoprotein. Men were more likely to have coronary heart disease and lower high-density lipoprotein and were more likely to be at goal at entry for triglyceride level. There were no gender differences in low-density lipoprotein at goal at entry or rate of current smoking. All lipid parameters appeared better with age, irrespective of gender. More men than women reached goal for their low-density lipoprotein (61.5% vs 51.7%) and triglyceride (36.9% vs 25.1%) levels, whereas more women than men reached goal for their high-density lipoprotein (33.1% vs 22.2%). The authors conclude that there are significant gender differences in lipid values at entry to a community lipid clinic and in achieving National Cholesterol Education Program targets following the initiation of therapy. A possible gender-independent survivorship effect exists for low-density lipoprotein and high-density lipoprotein.

Comparison of Efficacy and Safety of Rosuvastatin Versus Atorvastatin in African-American Patients in a Six-Week Trial

The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterol > or = 160 and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.

Cost-Effectiveness of Rosuvastatin Compared with Other Statins from a Managed Care Perspective

The objective of this study was to identify the most cost-effective statin or combination of statins, from the perspective of a managed care payer. A decision-analytic model compared the cost-effectiveness of titration to goal with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in patients with elevated low-density lipoprotein cholesterol (LDL-C). Effectiveness measures included the percentage change from baseline LDL-C and high-density lipoprotein cholesterol (HDL-C), and the percentage of patients achieving National Cholesterol Education Program (NCEP) Second Adult Treatment Panel (ATP II) LDL-C goals. Direct medical costs were calculated based on drug, physician, and laboratory resource use, multiplied by wholesale acquisition costs for drugs and the 2005 Medicare reimbursement rates for services. A Monte Carlo simulation tested the sensitivity of results to model efficacy inputs. In the base-case analysis, rosuvastatin dominated atorvastatin, pravastatin, and simvastatin. Generic lovastatin dominated fluvastatin. The incremental (absolute) reduction in LDL-C, increase in HDL-C, and increase in patients to goal with rosuvastatin compared with lovastatin were 16%, 3%, and 27%, respectively. Incremental costs per additional 1% reduction in LDL-C, 1% increase in HDL-C, and patient to goal with rosuvastatin versus lovastatin were $8, $41, and $436, respectively. A wide variety of assumptions were assessed and Monte Carlo sensitivity analyses were conducted. Findings were most sensitive to the cost of lovastatin. Rosuvastatin dominates atorvastatin, pravastatin, and simvastatin because it is more effective and less costly, and it may be considered cost-effective compared with generic lovastatin. The most cost-effective two-statin formulary contained lovastatin and rosuvastatin.

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

ABSTRACTBackground: International guidelines emphasize the need to achieve recommended low-density lipoprotein cholesterol (LDL‐C) levels in order to reduce morbidity and mortality associated with coronary heart disease (CHD). However, many patients with hypercholesterolemia fail to achieve LDL‐C goals on treatment.Objective: The primary objective was to compare the efficacy of rosuvastatin and atorvastatin for enabling patients to achieve National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL‐C goals. Secondary objectives were European LDL‐C goal achievement, changes in the lipid profile, and safety.Research design and methods: This 12‐week, multicenter, multinational, randomized, open-label trial compared the efficacy and safety of rosuvastatin 10 mg with atorvastatin 10 mg in statin-naïve and switched patients with primary hypercholesterolemia from Brazil, Colombia, Mexico, Portugal, and Venezuela.Results: A total of 1124 patients with similar baseline characteristics were randomized to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving rosuvastatin 10 mg compared with atorvastatin 10 mg achieved NCEP ATP III LDL‐C goals (71.2% vs 61.4%, p < 0.001), 1998 European LDL‐C goals (73.5% vs 59.2%, p < 0.001) and 2003 European LDL‐C goals (58.9% vs 44.6%, p < 0.001). Rosuvastatin treatment was associated with significant reductions in LDL‐C and total cholesterol (TC) and, in statin-naïve patients, a significant increase in high-density lipoprotein cholesterol (HDL‐C) compared with atorvastatin treatment. Both treatments were well tolerated with a similar incidence of adverse events. Clinically significant elevations in creatinine, creatine kinase or hepatic transaminases were low and similar between treatment groups.Conclusions: Rosuvastatin 10 mg is significantly more effective at achieving NCEP ATP III and European LDL‐C goals, lowering LDL‐C and TC in both naïve and switched patients and increasing HDL‐C in naïve patients than atorvastatin 10 mg, with a similar safety and tolerability profile. This study also provides evidence regarding the comparative effects of rosuvastatin versus atorvastatin in Latin American and Portuguese populations.

Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids in postmenopausal women with primary hypercholesterolemia

Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and 30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo). Each active treatment decreased non-HDL cholesterol compared with placebo ( P < .01). Coadministration treatment was more effective than either monotherapy in reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared with raloxifene, but was not significantly different when compared with simvastatin. Coadministration therapy increased HDL cholesterol and apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a) occurred with any active treatment. Raloxifene, simvastatin, and the coadministration therapy were generally well tolerated with clinical adverse effects similar to placebo. No woman had clinically significant elevated liver function tests requiring drug discontinuation. Further data on safety and lipid-lowering effects are needed before raloxifene and statin coadministration may be considered as therapeutic interventions for treating postmenopausal women to achieve National Cholesterol Education Program–Adult Treatment Panel III treatment guidelines.

Cost Effectiveness of Rosuvastatin in Treating Patients to Low-Density Lipoprotein Cholesterol Goals Compared With Atorvastatin, Pravastatin, and Simvastatin (a US Analysis of the STELLAR Trial)

Statin therapy decreases low-density lipoprotein cholesterol levels and the risk of coronary heart disease but has a considerable short-term effect on health care budgets. The cost effectiveness of rosuvastatin (Crestor) has been compared with those of atorvastatin, pravastatin, and simvastatin in lowering low-density lipoprotein cholesterol levels and achieving National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The analysis was conducted from the perspective of health care payers in the United States. Clinical data were obtained from the Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) trial. Drug costs were based on wholesale acquisition costs. Cost effectiveness was assessed with the net monetary benefit approach and a 1-year time horizon. Rosuvastatin at 10 mg, the recommended starting dose, was the most cost-effective statin over a large range of "willingness-to-pay" values for a unit of clinical effect (i.e., a 1% decrease in low-density lipoprotein cholesterol or a patient achieving the goal).

Achieving National Cholesterol Education Program Goals in Coronary Artery Disease

National Cholesterol Education Program (NCEP) guidelines recommend low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL for patients with coronary artery disease (CAD) and lipid-lowering therapy if LDL-C remains >100-130 mg/dL after dietary intervention. Studies consistently report that the majority of CAD patients do not achieve NCEP goals in clinical practice; we sought to determine if our practice fared better. We performed a retrospective chart review of 600 CAD patients followed by cardiologists. The mean age was 69, and 66% of patients were male. Of persons with a cardiology clinic lipid profile (60%), most (76%) achieved an LDL-C <100 mg/dL; however, only 61% were treated to the NCEP secondary goal of non-HDL-C <130 mg/dL. Of patients not at an LDL-C goal, 81% were on lipid-lowering therapy, but only 18% were on maximal statin doses and 6% on combination therapy. We concluded that the majority of CAD patients have had recent lipid measurements and are treated according to NCEP guidelines, but many patients remain on suboptimal therapy.

Rosuvastatin: a review of its use in the management of dyslipidemia.

Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment, rosuvastatin was significantly (all p < 0.05) more effective at milligram equivalent dosages than atorvastatin, pravastatin, and simvastatin in improving the overall lipid profiles of patients with hypercholesterolemia (intent-to-treat analyses). Moreover, overall a significantly (all p < 0.001) higher proportion of patients achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein-cholesterol (LDL-C) goals with rosuvastatin 10 mg/day than with therapeutic starting dosages of these other statins after 12 weeks' treatment in pooled analyses. Rosuvastatin treatment for up to 52 weeks was generally well tolerated in patients with dyslipidemias in clinical trials. The most commonly reported treatment-related adverse events were myalgia, constipation, asthenia, abdominal pain, and nausea; these were mostly transient and mild. The incidence of proteinuria or microscopic hematuria with rosuvastatin 10 or 20 mg/day was <1% versus <1.5% with rosuvastatin 40 mg/day; these events were mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. Importantly, very few patients experienced elevations in serum creatine phosphokinase (CPK) levels of over [corrected] 10-fold the upper limit of normal (0.2-0.4% of patients) or treatment-related myopathy (<or=0.1%) [i.e. muscle aches or weakness plus the same elevated serum CPK levels] at dosages of 5-40 mg/day. In conclusion, rosuvastatin treatment effectively and rapidly improves the lipid profile in patients with a broad spectrum of dyslipidemias. In those with hypercholesterolemia (including high-risk patients), rosuvastatin was more efficacious than and generally as well tolerated as atorvastatin, simvastatin, and pravastatin, with significantly more rosuvastatin recipients achieving their NCEP ATP III target LDL-C levels. Thus, rosuvastatin has emerged as a valuable choice for first-line treatment in the management of low- to high-risk patients requiring lipid-lowering drug therapy.

Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged ≥18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for ≥6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of −25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides −14.0%) compared with LDL cholesterol −3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides −2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.

Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels

Apolipoprotein B has been shown to be a better predictor of coronary heart disease than low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol may also be a better parameter for coronary heart disease risk assessment and as a target for therapy. Data from the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) were used to assess the correlation between lipid and apolipoprotein B levels before and after lipid-lowering therapy and to examine the effects of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on lipids and apolipoprotein B. The 54-week study randomized 3,916 hypercholesterolemic patients to atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin, initiated at recommended starting doses with titrations as needed at weeks 6, 12, and 18 to achieve National Cholesterol Education Program LDL targets. Compared with LDL cholesterol, non-HDL cholesterol correlated better with apolipoprotein B levels at baseline (r = 0.914, p <0.0001) and at week 54 (r = 0.938, p <0.0001), and the correlation was strong across all baseline triglyceride strata. At starting doses, atorvastatin (10 mg) lowered non-HDL cholesterol by 33.3% compared with 26.6% with simvastatin (10 mg), 24.1% with lovastatin (20 mg), 17.2% with fluvastatin (20 mg), and 17.0% with pravastatin (10 mg). Atorvastatin also provided greater reductions in non-HDL cholesterol after dose titration, and a greater percentage of patients taking atorvastatin achieved non-HDL cholesterol targets. Baseline triglyceride did not affect non-HDL cholesterol reductions with any of the 5 hydroxymethylglutaryl coenzyme A reductase inhibitors. Fewer patients achieved non-HDL cholesterol targets than LDL cholesterol targets, particularly among high-risk patients, implying that if non-HDL cholesterol was used as a target for treatment, more patients would need to be treated more aggressively than National Cholesterol Education Program guidelines require.

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

Background Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. Methods and Results We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C ≤160 mg/dL [4.1 mmol/L] if <2 CHD risk factors and LDL-C ≤130 mg/dL [3.4 mmol/L] if ≥2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C ≤100 mg/dL (2.6 mmol/L) with 10 mg and 60% reached this target with up to 20 mg of atorvastatin. With maximal titration to the LDL-C target, up to and including 80 mg atorvastatin, 87% of women without CVD and 80% of women with established CVD achieved LDL-C targets. The presence of mixed dyslipidemia with obesity did not affect the frequency of achieving LDL-C targets. Conclusion: Atorvastatin is very effective in achieving National Cholesterol Education Program Adult Treatment Panel II target concentrations for LDL-C in the majority of women with established CVD or CVD risk factors. (Am Heart J 2001;141: 949-56.)