Rosuvastatin

Abstract

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 5–40mg 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 10-fold the upper limit of normal (0.2–0.4% of patients) or treatment-related myopathy (≤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.

Pharmacodynamic Properties

Rosuvastatin is a single enantiomeric hydroxy acid that is administered as the calcium salt. The drug has a relatively low lipophilicity. Rosuvastatin has a high affinity for the active site of HMG-CoA reductase activity. In in vitro and in vivo studies, rosuvastatin typically inhibits HMG-CoA reductase and cholesterol synthesis to a significantly greater extent than other statins. Rosuvastatin is selectively taken up by hepatic cells in vitro and in vivo, with minimal uptake by nonhepatic cells. Rosuvastatin has a high affinity for the predominantly hepatic organic anion transport protein C. Rosuvastatin increases clearance of plasma low-density lipoprotein-cholesterol (LDL-C) by upregulation of hepatic LDL-C receptors and affects LDL production by decreasing hepatic production of very low-density lipoprotein. In healthy volunteers, rosuvastatin 10 mg/day reduced serum LDL-C (44.2%), total cholesterol (31.8%), triglycerides (22.7%), and apolipoprotein (Apo) B (35.3%). Rosuvastatin was equally effective in lowering serum LDL-C following morning or evening administration. Non-lipid-lowering effects, such as improvements in endothelial function, anti-inflammatory effects, vasculo-protective and cardio/cerebro-protective effects, and improvements in neural function have been reported in in vivo and in vitro studies.

Pharmacokinetic Properties

The Pharmacokinetic properties of rosuvastatin are dose-proportional, with little or no accumulation after repeated administration. Maximum rosuvastatin plasma concentrations of 19–25 μg/L are reached 3–5 hours after administration of a single oral dose of rosuvastatin 40mg in healthy volunteers. The absolute bioavailability of rosuvastatin is approximately 20%. Food decreases the rate of rosuvastatin absorption by 20%, but the extent of absorption remains unchanged. At steady state, the mean volume of distribution of rosuvastatin is approximately 134L. Rosuvastatin is reversibly bound to plasma proteins (88%). Rosuvastatin undergoes very limited metabolism (≈10% of radiolabelled drug recovered as metabolites from urine), with metabolism primarily occurring via cytochrome P450 (CYP) 2C9. N-desmethyl rosuvastatin is the major metabolite. Rosuvastatin undergoes predominantly biliary excretion, with 90% of a single oral dose of radioactive rosuvastatin recovered in the feces (92% as the parent compound). The plasma elimination half-life of rosuvastatin after a single oral dose of rosuvastatin 40mg is 18 24 hours. There were no clinically relevant changes in the pharmacokinetics of rosuvastatin with differences in patient age or gender, time of administration, or mild to moderate renal impairment. However, plasma concentrations of rosuvastatin were increased in patients with severe renal impairment. Rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve values were increased in patients with mild to moderate hepatic impairment. Coadministration of rosuvastatin and ketoconazole, erythromycin, itraconazole (inhibitors of CYP3A4), fenofibrate, fluconazole (metabolized by CYP2C9 and CYP2C19), or digoxin had no clinically relevant effect on the pharmacokinetics of rosuvastatin. Coadministration of rosuvastatin and warfarin increased the International Normalized Ratio. Concomitant rosuvastatin plus cyclosporine or gemfibrozil resulted in a clinically relevant increase in systemic exposure to rosuvastatin. Administration of antacid 2 hours after rosuvastatin avoided clinically relevant decreases in plasma concentrations of rosuvastatin. Administration of contraceptives (ethinyl estradiol and norgestrel) and rosuvastatin increased the plasma concentrations of ethinyl estradiol and norgestrel by 26% and 34%.

Therapeutic Efficacy

Treatment with oral rosuvastatin 5–40mg once daily effectively and rapidly improved lipid profiles across a broad spectrum of patients with dyslipidemias in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks’ duration. In well-designed trials of 6–12 weeks’ duration in patients with hypercholesterolemia, rosuvastatin (5 and 10 mg/day) recipients achieved significantly (all p < 0.05) greater improvements in plasma LDL-C and total cholesterol levels than those receiving atorvastatin 10 mg/day, pravastatin 20 mg/day or simvastatin 20 mg/day, according to primary endpoint intent-to-treat analyses. All other aspects of the lipid profile improved to the same or a greater extent with rosuvastatin treatment than with these other statins, including increases in plasma high-density lipoprotein-cholesterol (HDL-C) levels and reductions in plasma Apo B, triglycerides, and non-HDL-C levels. As assessed in individual trials and pooled analyses, these improvements were in turn reflected in significantly greater improvements in lipid ratios of atherogenic to non-atherogenic lipid components (e. g. LDL-C: HDL-C, non-HDL-C: HDL-C, Apo B: Apo A1 ratios) with rosuvastatin treatment relative to other statins. Notably, rosuvastatin treatment proved effective, irrespective of the patient’s age, gender, postmenopausal status, and/or the presence of type 2 diabetes mellitus with or without metabolic syndrome, hypertension, atherosclerosis, and/or obesity. Pooled analyses indicated that overall a significantly (all p < 0.001) higher proportion of patients achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL-C goals with rosuvastatin 10 mg/day than with therapeutic starting dosages of other statins after 12 weeks’ treatment, with 80% of rosuvastatin 10 mg/day recipients achieving their goals. Rosuvastatin 10 mg/day was significantly (all p < 0.05) more effective than simvastatin 20 mg/day or pravastatin 20 mg/day based on individual NCEP ATP III goals: LDL-C target <100 mg/dL 63%, 22%, and 5% of patients achieved target, respectively; LDL-C target <130 mg/ dL 89%, 74%, and 40%; and LDL-C target <160 mg/dL 99%, 90%, and 88%. Relative to atorvastatin 10 mg/day recipients, significantly more rosuvastatin 10 mg/day recipients achieved their target of <100 mg/dL (60% vs 19% in the atorvastatin group; p < 0.05), although response rates were not statistically different in those with targets of <130 mg/dL (88% vs 80%) or <160 mg/dL (96% vs 91%). Results of the STELLAR (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin) trial confirmed data from these pooled analyses. In the 16-week MERCURY I (Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY) trial, patients who switched from previous statin treatment to rosuvastatin 10 mg/day achieved significantly (all p < 0.0001) greater reductions in plasma LDL-C than those who continued to receive atorvastatin 10 mg/day (46.2% vs 38.5% reduction), simvastatin 20 mg/day (45.6% vs 37.4%) or pravastatin 40 mg/day (46.6% vs 32.4%). Improvements in lipid parameters that were observed after switching to rosuvastatin were generally reflected in significantly (all p ≤ 0.0001) greater reductions in lipid ratios for LDL-C: HDL-C, non-HDL-C: HDL-C, and Apo B: Apo A1. Furthermore, significantly more patients who switched to rosuvastatin 10 mg/day at 8 weeks achieved NCEP ATP III LDL-C targets than those who remained on existing treatment. In difficult-to-treat patient populations, such as those with type 2 diabetes with mixed dyslipidemia, combining rosuvastatin with fenofibrate enhanced reductions in plasma triglyceride levels versus rosuvastatin monotherapy. However, combining rosuvastatin 40 mg/day with niacin extended-release (ER) 1 g/day had no additional benefit in terms of reduction in atherogenic lipid parameters to those achieved with the equivalent dosage of rosuvastatin monotherapy in patients with Fredrickson type IIb or IV hyperlipidemia, although mean plasma HDL-C levels increased by a significantly greater extent with rosuvastatin 10 mg/day plus niacin ER 2 g/ day than with rosuvastatin 40 mg/day monotherapy (11% vs 24%; p < 0.001).

Tolerability

Rosuvastatin was generally well tolerated in clinical trials of up to 1 year’s duration, with tolerability data based on pooled analyses and extension phases of these trials. Overall, in clinical trials the most commonly reported adverse events possibly or probably related to rosuvastatin treatment were myalgia, constipation, asthenia, abdominal pain, and nausea (incidence not reported). Most adverse events were of mild intensity and transient, with 3.7% of 10 275 rosuvastatin recipients discontinuing treatment because of a drug-related adverse event. No rosuvastatin-related deaths occurred during participation in clinical trials. A few rosuvastatin recipients have developed proteinuria (<1% of patients receiving rosuvastatin 10 or 20 mg/day and <1.5% of 40 mg/day recipients) and microscopic hematuria, with these effects generally being mild, mostly transient, possibly tubular in origin, and not associated with acute or progressive deterioration in renal function. There was usually no change or a decrease in mean serum creatinine levels from baseline with rosuvastatin 10–40 mg/day treatment for up to 96 weeks. Notably, in controlled clinical trials with rosuvastatin 5–40 mg/day, 0.2–0.4% of patients experienced elevations in serum creatine phosphokinase (CPK) levels of over 10-fold the upper limit of normal, whereas ≤0.1% of recipients experienced treatment-related myopathy (i. e. muscle aches or weakness plus elevated serum CPK levels of over 10-fold the upper limit of normal); these incidences were similar to those reported with other statins. In clinical trials, rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria occurred with rosuvastatin treatment at the higher-than-recommended 80mg dose. Overall, rosuvastatin 10–40 mg/day had a similar tolerability profile to that of atorvastatin 10–80 mg/day, simvastatin 10–80 mg/day, or pravastatin 10–40 mg/day in controlled clinical trials (nature and incidence of adverse events not reported), with 2.9%, 3.2%, 2.5%, and 2.5% of recipients, respectively, discontinuing treatment because of a treatment-related adverse event. As with rosuvastatin 10 or 20 mg/day, less than 1% of patients experienced a positive dipstick test for proteinuria at the final visit with atorvastatin 10–80 mg/day, simvastatin 10–80 mg/day, and pravastatin 10–40 mg/day, with a numerically higher incidence (<1.5%) in those receiving rosuvastatin 40 mg/day. In addition, rare cases (0.2% of patients) of clinically relevant elevations in serum ALT levels have occurred with rosuvastatin ≤80 mg/day, atorvastatin ≤80 mg/day, simvastatin ≤80 mg/ day, or pravastatin ≤40 mg/day. Rosuvastatin (40 mg/day) was as well tolerated as niacin ER (2 g/day) monotherapy in patients with mixed dyslipidemia, with numerically fewer rosuvastatin (n = 46) than niacin ER recipients (n = 72) experiencing treatment-related adverse events (28.3% vs 59.7%). The most common treatment-related adverse events in the rosuvastatin and niacin ER monotherapy groups were flushing (0% vs 43.1%), pruritus (0% vs 13.9%), rash (0% vs 6.9%), paresthesia (0% vs 2.8%), and myalgia (6.5% vs 1.4%). Limited data also indicate that rosuvastatin (5 or 10 mg/day) plus fenofibrate (201 mg/day) combination therapy was as well tolerated as treatment with the same dosages of the individual agents in a 24-week study.

Dosage and Administration

Rosuvastatin is indicated for the treatment of patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson type IIa and IIb) as an adjunct to diet. The recommended dosage is 5–40mg once daily. Rosuvastatin 40 mg/day should only be administered to patients unable to achieve LDL-C goals with 20 mg/day. The drug may be taken without regard to food, with the dosage individualized based on the patient’s response, LDL-C goal, presence of other comorbid conditions, and/or whether the individual is receiving concomitantly administered drugs. Rosuvastatin is also indicated in patients with elevated triglyceride levels (Fredrickson type IV) as an adjunct to diet (recommended dosages not reported in US prescribing information), and in those with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments such as LDL apheresis. Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy. Liver function tests should be performed before treatment commences and at key timepoints throughout the treatment. Dosage reduction should be considered for those receiving rosuvastatin 40 mg/day with persistent unexplained proteinuria. Rosuvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases, and in pregnant women and breastfeeding mothers.     

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

Background

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.

Objectives

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.

Methods

The following treatments were evaluated: rosuvastatin 5–20mg/day; atorvastatin, simvastatin, and pravastatin 10–40mg/day; lovastatin and fluvastatin 20–80mg/day; and combination therapy with a statin plus either cholestyramine 12–24g/day or ezetimibe 10mg/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.

Results

The effectiveness in terms of percentage reduction in LDL-C ranged from 19% for pravastatin 10mg/day to 55% for atorvastatin 80mg/day. Annual treatment costs ranged from €189.7 for simvastatin 10mg/day to €759.3 for atorvastatin 80mg/day. The cost-effectiveness ratios, in terms of cost per percentage point reduction in LDL-C, were: €6 for simvastatin, €10–12 for rosuvastatin, €10 for lovastatin, €13–16 for atorvastatin, €13–14 for fluvastatin, and €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 €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 €217 and €190, respectively.

Conclusion

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.     

Effect of Atorvastatin Versus Rosuvastatin on Levels of Serum Lipids,Inflammatory Markers and Adiponectin in Patients with Hypercholesterolemia

Purpose  To compare the short-term effect of treatment with atorvastatin and rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. Methods  Sixty-nine patients with hypercholesterolemia were randomly assigned to receive 10 mg/day of atorvastatin or rosuvastatin for 12 weeks. Inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9), and endothelin (ET-1), plasminogen activator inhibitor type 1 (PAI-1) and plasma tissue plasminogen activator (tPA), adiponectin, and lipid profiles were measured before and after statin therapy. Results  Atorvastatin and rosuvastatin both lowered levels of hs-CRP, MMP-9, PAI-1, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) from baseline values, with rosuvastatin lowering TC and LDL-C to a greater extent than atorvastatin (P < 0.05). Adiponectin level increase was 15% higher than that at baseline with atorvastatin (P > 0.05) but 67% higher with rosuvastatin (P < 0.05). Conclusions  Therapy with both statins not only significantly improved lipid profiles but also decreased levels of vascular biomarkers hs-CRP, MMP-9, and PAI-1; however, only rosuvastatin increased serum adiponectin levels significantly in patients with hypercholesterolemia, which could imply a beneficial effect in coronary artery disease.     

阿托伐他汀与瑞舒伐他汀对冠心病患者的疗效与安全性对比观察

目的:对比分析阿托伐他汀与瑞舒伐他汀在冠心病患者中应用的疗效与安全性。方法:回顾性分析127例冠心病患者的临床资料,根据调脂药物的种类分为2组:阿托伐他汀组44例,基本用量20 mg·d^-1,用药(7.6±1.9)个月;瑞舒伐他汀组83例,基本用量10 mg·d^-1,用药(7.9±2.1)个月。分别统计治疗前、治疗后1,2,4,8,12周及末次复查时血脂水平,并记录药物不良反应。结果:患者接受药物治疗1周时各指标较治疗前均无明显变化(P>0.05);治疗2周时,两组TG、TC及LDL-C水平均较治疗前降低(P<0.05),但组间差异无统计学意义(P>0.05);药物治疗4,8,12周时,两组TG、TC及LDL-C较治疗前降低(P<0.05),瑞舒伐他汀组LDL-C水平低于阿托伐他汀组,而LDL-C的降幅和血脂达标率均高于阿托伐他汀组,差异均有统计学意义(P<0.05)。至末次复查,两组TG、TC及LDL-C均较基线水平显著降低(P<0.05),阿托伐他汀组LDL-C的降幅低于瑞舒伐他汀组(P<0.05)。两组共发生药物相关性不良反应9例,其中阿托伐他汀组4例(9.1%),瑞舒伐他汀组5例(6.0%),两组差异无统计学意义(P>0.05)。结论:瑞舒伐他汀和阿托伐他汀均于用药2周时表现出较好的调脂疗效,10 mg·d^-1瑞舒伐他汀的调脂疗效优于20 mg·d^-1阿托伐他汀,两药不良反应发生率均较低,安全性无明显差异。     

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

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.     

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

BACKGROUND: The ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL-C/HDL-C) is a reliable predictor of cardiovascular risk. Low HDL-C levels in patients with coronary artery disease are associated with a high risk for cardiovascular events. OBJECTIVES: This study compared the effects of rosuvastatin and atorvastatin on the LDL-C/HDL-C. METHODS: Patients aged 40-80 years with established cardiovascular disease and HDL-C < 1.0 mmol/L (< 40 mg/dL) entered as a 6-week dietary run-in period, before randomisation to open-label treatment with rosuvastatin 10 mg (n = 230) or atorvastatin 20 mg (n = 231) for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg, and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg. Serum lipid parameters were measured at baseline and 6, 12 and 18 weeks. RESULTS: After 6 weeks of treatment, mean percentage change from baseline in LDL-C/HDL-C ratio was -47.0% in the rosuvastatin group and -41.9% in the atorvastatin group (p < 0.05 for between-group comparison). After 12 and 18 weeks of treatment, change from baseline was -53.0% and -57.3%, respectively, for rosucastatin, compared with -47.9% and -49.6%, respectively, for atorvastatin (p < 0.01 and p < 0.001, respectively, for between-group comparison). Rosuvastatin also reduced LDL-C, total cholesterol/HDL-C significantly more than atorvastatin at all three time points, and significantly improved total cholesterol/HDL-C and apolipoprotein B/A-I ratios. CONCLUSIONS: Rosuvastatin 10, 20 and 40 mg is significantly more effective than atorvastatin 20, 40 and 80 mg, respectively, in improving the LDL-C/HDL-C ratio in patients with cardiovascular disease and low HDL-C. Further studies are required to clarify the benefits of rosuvastatin for reduction of cardiovascular risk.     

Cost-Effectiveness Analysis of Cholesterol-Lowering Therapies in Spain

OBJECTIVE: To assess the cost efficacy of atorvastatin, simvastatin, lovastatin, fluvastatin, pravastatin, and colestyramine in the reduction of low-density lipoprotein-cholesterol (LDL-C) levels and the cost per patient to achieve the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) therapeutic objectives in Spain. METHOD: The following treatments were evaluated: atorvastatin, simvastatin, and pravastatin 10-40 mg/day; lovastatin and fluvastatin 20-80 mg/day; and colestyramine 12-24 g/day. The cost effectiveness of these treatments was evaluated, in terms of cost per percentage of LDL-C reduction, by comparing annual treatment costs versus the efficacy of LDL-C reduction. Treatment costs included medication costs (2003 wholesale prices), control measures, and the treatment of adverse affects. The efficacy of HMG-CoA reductase inhibitors (statins) was obtained from a meta-analysis of results obtained from clinical trials published between 1993 and 2003 that met the following criteria: monotherapy; >16 weeks of treatment; randomized allocation of individuals to the intervention and comparator groups; dietary treatment for > or =3 months before administration of medication; and double-blind measurement of outcomes. Average and incremental cost-effectiveness ratios were calculated to assess the efficiency of cholesterol-lowering treatments. RESULTS: Efficacy, in terms of percentage of LDL-C reduction, ranged from 10% for colestyramine 12 g/day to 49% for atorvastatin 40 mg/day. Total annual treatment costs ranged from euro 321 for fluvastatin 20 mg/day to euro 1151 for atorvastatin 40 mg/day. Cost-effectiveness ratios, in terms of cost per percentage of LDL-C reduced, were: euro 11-23 for atorvastatin; euro 12-21 for simvastatin; euro 14-22 for lovastatin; euro 15-24 for fluvastatin; euro 21-42 for pravastatin; and euro 35-46 for colestyramine. Atorvastatin 10 mg/day was the most cost-effective treatment, followed by simvastatin 10 mg/day, lovastatin 20 mg/day, and fluvastatin 20 mg/day. Atorvastatin was the most cost-effective treatment in the achievement of the NCEP ATP III LDL-C reduction objectives in patients with high (<100 mg/dL) and moderate (<130 mg/dL) risk of coronary heart disease (CHD), with a cost per patient of euro 747 and euro 405 per year, respectively. Fluvastatin was the most cost-effective treatment in the achievement of the NCEP ATPIII therapeutic objective in patients with low-risk of CHD (LDL-C <160 mg/dL), with a cost per patient of euro 321. CONCLUSION: Atorvastatin 10 mg/day was the most cost-effective cholesterol-lowering drug, followed by simvastatin 10 mg/day, lovastatin 20 mg/day, and fluvastatin 20 mg/day. The preferred statin should be atorvastatin in patients with moderate-to-high CHD risk and fluvastatin in patients with low risk for CHD.     

瑞舒伐他汀钙治疗原发性高胆固醇血症的有效性和安全性II期临床试验

目的:评价不同起始剂量的瑞舒伐他汀钙治疗原发性高胆固醇血症患者的有效性和安全性.方法:采用多中心、随机、双盲、双模拟、阳性药平行对照临床试验设计,经4周安慰剂导入和饮食控制期后筛选出符合入选条件的患者进入为期8周的不同起始剂量的药物(分别给予瑞舒伐他汀钙5或10 mg、或阿托伐他汀钙10 mg)治疗期.治疗至第4周末时,如患者的低密度脂蛋白胆固醇(LDL-C)≥3.12 mmol/L(120 mg/dl),则所服药物剂量加倍.结果:治疗8周后,各组LDL-C水平均较基线时明显下降(P＜0.05),且瑞舒伐他汀钙10 mg组与阿托伐他汀钙10 mg组间的差异有统计学意义(P＜0.05).以相差5个百分点为非劣效判断标准,发现瑞舒伐他汀钙5和10 mg两组降低LDL-C水平的疗效均不劣于阿托伐他汀钙10 mg组.结论:瑞舒伐他汀钙5和10 mg治疗在中国人群中的降脂疗效与阿托伐他汀10 mg相当,均具有良好的安全性和耐受性.     

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

BACKGROUND: International guidelines emphasize the need to achieve recommended low-density lipoprotein cholesterol (LDL-C) levels in order to reduce morbidity and mortality associated with coronary heart disease (CHD). However, many patients with hypercholesterolemia fail to achieve LDL-C goals on treatment. OBJECTIVE: The primary objective was to compare the efficacy of rosuvastatin and atorvastatin for enabling patients to achieve National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals. Secondary objectives were European LDL-C goal achievement, changes in the lipid profile, and safety. RESEARCH DESIGN AND METHODS: This 12-week, multicenter, multinational, randomized, open-label trial compared the efficacy and safety of rosuvastatin 10 mg with atorvastatin 10 mg in statin-na?ve 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-na?ve 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 na?ve and switched patients and increasing HDL-C in na?ve patients than atorvastatin 10mg, 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.     

Fenofibric Acid

? Fenofibric acid activates peroxisome proliferator-activated receptor α to modify fatty acid and lipid metabolism. Fenofibric acid is the first member of the fibric acid derivatives (fibrates) class approved for use as combination therapy with HMG-CoA reductase inhibitors (statins). ? In three randomized, double-blind, multicenter, phase III trials in adult patients with mixed dyslipidemia, up to 12 weeks’ treatment with once-daily fenofibric acid 135 mg plus a low- or moderate-dose statin (atorvastatin 20 or 40 mg, rosuvastatin 10 or 20 mg, or simvastatin 20 or 40 mg) improved high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels to a significantly greater extent than statin monotherapy, and improved low-density lipoprotein cholesterol (LDL-C) levels to a significantly greater extent than fenofibric acid monotherapy. ? In a 52-week, open-label, multicenter, extension study, HDL-C, TG, and LDL-C levels continued to improve, or were maintained, during combination therapy with once-daily fenofibric acid 135 mg plus a moderate-dose statin (atorvastatin 40 mg, rosuvastatin 20 mg, or simvastatin 40 mg). ? Once-daily fenofibric acid 135 mg plus a statin was generally as well tolerated as monotherapy with fenofibric acid 135 mg/day or the corresponding statin dosage in the three phase III trials in patients with mixed dyslipidemia. The incidence of adverse events was similar between the combination therapy group and both monotherapy groups. ? In the extension trial, once-daily fenofibric acid 135 mg plus a moderate-dose statin (atorvastatin 40 mg, rosuvastatin 20 mg, or simvastatin 40 mg) for up to 52 weeks was generally well tolerated.     

Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia

BACKGROUND: Hypercholesterolaemia is a risk factor for coronary heart disease (CHD). Clinical studies have shown that lowering elevated serum total cholesterol (TC) levels, and particularly low density lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary morbidity and deaths, whereas high serum levels of high density lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic dosage range from 5-20 mg/day. Atorvastatin is an HMG-CoA reductase inhibitor which across its dosage range (10-80 mg/day) has shown significantly greater lipid-lowering effects than all previously marketed statins. OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of policosanol with atorvastatin in older patients with type II hypercholesterolaemia. PATIENTS AND METHODS: This randomised, single-blind, parallel-group study was conducted in older patients (60-80 years) with type II hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet, 75 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. An interim and final check-up were performed at 4 and 8 weeks, respectively, after treatment was initiated. RESULTS: At 4 (p < 0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline; corresponding values for atorvastatin were 28.4 and 29.8%. At study completion, policosanol significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were well tolerated. At study completion, atorvastatin mildly, but significantly (p < 0.05) increased creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced AST and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values, however, remained within normal limits. Three atorvastatin but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01). CONCLUSIONS: This study shows that policosanol (10 mg/day) administered for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing serum LDL-C and TC levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-C levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides. Policosanol was better tolerated than atorvastatin as revealed by patient withdrawal analysis and overall frequency of adverse events. Nevertheless, further studies must be conducted in larger sample sizes and using dose-titration methods to achieve target lipid levels in order to reach wider conclusions.     

LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results*

ABSTRACT

Objective: The effectiveness of statin therapy in a real life setting may differ from that in clinical trials, as physicians make non-randomised treatment decisions for patients with less uniform and possibly different characteristics. We therefore performed a study to compare the effectiveness of different statins and doses in routine clinical practice with respect to total serum cholesterol and LDL-cholesterol (LDL-C) reduction and goal attainment according to European guidelines on the prevention of cardiovascular disease (CVD).

Research design and methods: Naive statin users starting treatment in 2003 and 2004 with LDL-C measurements at baseline and between 30 and 365 days after start of treatment were extracted from the PHARMO database. During treatment with their initial statin dose LDL-C reduction and attainment of cholesterol goals were compared between different statins and doses.

Results: Of 2303 identified naive patients, approximately 30% were allocated to the high CVD-risk group. Average LDL-C reductions were 48%, 42%, 39%, and 32% at mean doses of 11 mg rosuvastatin, 17 mg atorvastatin, 22 mg simvastatin and 35 mg pravastatin, respectively. The proportion of patients attaining cholesterol goals was 75% for rosuvastatin, 68% for atorvastatin, 56% for simvastatin, and 42% for pravastatin. Dose comparisons showed greater LDL-C reduction and increased goal attainment for rosuvastatin 10 mg compared to other statins at most doses (adjusted p < 0.05).

Conclusions: In a real life setting, both LDL-C reduction and the proportion of patients attaining cholesterol goals appear to be significantly increased among users of rosuvastatin compared to other statins. These results confirm and extend reported clinical trial results to a real world setting.     

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

ABSTRACT

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

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

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

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

Comparison of efficacy,safety, and cost-effectiveness of various statins in dyslipidemic diabetic patients

Background and Aim:

To determine efficacy safety and the cost effectiveness, of the four most commonly prescribed statins (rosuvastatin, atorvastatin, pravastatin, and simvastatin) in the treatment of dyslipidemia among diabetic patients.

Materials and Methods:

This is a cohort, observational, population-based study conducted at diabetic clinics of the Hamad Medical Hospital and Primary Health Care Centers (PHCC) over a period from January 2007 to September 2012. The study included 1,542 consecutive diabetes patients above 18 years of age diagnosed with dyslipidemia and prescribed any of the indicated statins. Laboratory investigations were taken from the Electronic Medical Records Database (EMR-viewer). The sociodemographic, height, weight, and physical activities were collected from Patient''s Medical Records. Information about statin was extracted from the pharmacy drug database. The effective reductions in total cholesterol using rosuvastatin with atorvastatin, simvastatin, and pravastatin in achieving cholesterol goals and improving plasma lipids in dyslipidemic diabetic patients were measured. Serum lipid levels measured a 1 week before the treatment and at the end 2^nd year.

Results:

Rosuvastatin (10 mg) was the most effective in reducing low-density lipoprotein cholesterol (LDL-C; 28.59%), followed by simvastatin 20 mg (16.7%), atorvastatin 20 mg (15.9%), and pravastatin 20 mg (11.59.3%). All statins were safe with respect to muscular and hepatic functions. Atorvastatin was the safest statin as it resulted in the least number of patients with microalbuminuria (10.92%) as compared to other statins. Treatment with rosuvastatin 10 mg was more effective in allowing patients to reach European and Adult Treatment Plan (ATP) III LDL-C goals as compared to other statins (P < 0.0001) and produced greater reductions in LDL-C, total cholesterol, and non-HDL-C, produced similar or greater reductions in triglycerides (TGs) and increased in HDL-C.

Conclusion:

Rosuvastatin 10 mg was the most effective statin in reducing serum lipids and total cholesterol in dyslipidemic diabetic patients.KEY WORDS: Atorvastatin, cost effective, dyslipidemic diabetic patients, efficacy, pravastatin, rosuvastatin, safety of statin use in dyslipidemic diabetic patients, safety, simvastatin     

瑞舒伐他汀钙治疗原发性高胆固醇血症的有效性和安全性Ⅱ期临床试验

目的：评价不同起始剂量的瑞舒伐他汀钙治疗原发性高胆固醇血症患者的有效性和安全性。方法：采用多中心、随机、双盲、双模拟、阳性药平行对照临床试验设计,经4周安慰剂导入和饮食控制期后筛选出符合入选条件的患者进入为期8周的不同起始剂量的药物（分别给予瑞舒伐他汀钙5或10mg、或阿托伐他汀钙10mg）治疗期。治疗至第4周末时,如患者的低密度脂蛋白胆固醇（LDL—C）≥3．12mmol／L（120mg／d1）,则所服药物剂量加倍。结果：治疗8周后,各组LDL—C水平均较基线时明显下降（P〈0．05）,且瑞舒伐他汀钙10mg组与阿托伐他汀钙10mg组间的差异有统计学意义（P〈0．05）。以相差5个百分点为非劣效判断标准,发现瑞舒伐他汀钙5和10mg两组降低LDL—C水平的疗效均不劣于阿托伐他汀钙10mg组。结论：瑞舒伐他汀钙5和10mg治疗在中国人群中的降脂疗效与阿托伐他汀10mg相当,均具有良好的安全性和耐受性。     

普罗布考联合阿托伐他汀对急性冠脉综合征血脂蛋白相关磷脂酶A2的影响

目的:评价普罗布考和阿托伐他汀联合应用对急性冠脉综合征(ACS)患者血脂及脂蛋白相关磷脂酶A2(Lp-PLA2)的影响.方法:将94例经冠脉造影证实的ACS患者随机分为2组:单药组48例,予以阿托伐他汀(20 mg/d)治疗;联合组46例,予以阿托伐他汀(20 mg/d)和普罗布考(500 mg/d)联合治疗.分别于治疗前和治疗后6～8周检测血Lp-PLA2和血总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平并进行比较分析.结果:2组治疗前TC、TG、LDL-C、HDL-C、Lp-PLA2水平比较差异无统计学意义(P＞0.05);2组治疗后TC、TG、LDL-C、Lp-PLA2较治疗前均降低,单药组治疗后HDL-C升高,联合组治疗后HDL-C下降,差异均有统计学意义(P＜0.01);联合组较单独治疗组治疗后TC、LDL-C、Lp-PLA2降低,差异均有统计学意义(P＜0.05),但TG差异无统计学意义(P＞0.05).结论:对ACS患者单独应用阿托伐他汀及联合普罗布考均能够有效降低TC、LDL-C、Lp-PLA2,但联合治疗疗效更为显著,对稳定斑块、抗动脉粥样硬化有重要意义.     

瑞舒伐他汀对急性心肌梗死患者血清炎症因子和脂联素水平的影响

目的比较瑞舒伐他汀与阿托伐他汀对急性心肌梗死（AMI）患者的血清胆固醇（TC）、低密度脂蛋白（LDL-C）、高敏c反应蛋白（hs-CRP）、可溶性白细胞分化抗原40配体（sCD40L）和脂联素（APN）水平的影响。方法选择54例AMI患者,随机分为瑞舒伐他汀组（瑞舒伐他汀10～20mg,qd,28例）和阿托伐他汀组（阿托伐他汀20-40mg,qa,26例）,分别检测治疗前及治疗4周后2组患者TC、LDL-C、hs—CRP、sCD40L和APN水平。结果瑞舒伐他汀组和阿托伐他汀组治疗后血清,TC、LDL-C、hs-CRP、sCD40L水平较治疗前明显降低,APN水平明显升高,差异有统计学意义（P〈0．05）。治疗4周后瑞舒伐他汀组血清hs-CRP、sCD40L水平与阿托伐他汀组相比明显降低,APN水平明显升高,差异有统计学意义（P〈0．05）。结论瑞舒伐他汀和阿托伐他汀都能降低TC、LDL-C、sCD40L、hs—CRP水平,升高APN水平,但瑞舒伐他汀治疗急性心肌梗死的效果明显优于阿托伐他汀。     

Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial

In the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial, the efficacy of rosuvastatin calcium (Crestor) was compared with that of atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) for lowering plasma low-density lipoprotein cholesterol (LDL-C) after 6 weeks of treatment. In this multicenter, parallel-group, open-label trial, adults with hypercholesterolemia were randomized to treatments with rosuvastatin 10, 20, 40, or 80 mg, atorvastatin 10, 20, 40, or 80 mg, simvastatin 10, 20, 40, or 80 mg, or pravastatin 10, 20, or 40 mg. Efficacy and safety results from this trial have been previously published. The additional analyses included in this report show that 53% (83/156) to 80% (125/157) of patients in the rosuvastatin 10- to 40-mg groups achieved LDL-C levels < 100 mg/dl (< 2.6 mmol/l), compared with 18% (28/158) to 70% (115/165) of patients who received atorvastatin, 8% (13/165) to 53% (86/163) of patients who received simvastatin, and 1% (1/160) to 8% (13/161) of patients who received pravastatin. Other additional analyses showed that more patients in the rosuvastatin 10- to 40-mg groups than in the comparator groups who were at high risk of coronary heart disease according to National Cholesterol Education Program Adult Treatment Panel (ATP) III, Joint European Societies, or Canadian guidelines achieved the LDL-C goals of < 100 mg/dl (< 2.6 mmol/l) (55% to 77% compared with 0 to 64%), < 3.0 mmol/l (< 116 mg/dl) (76% to 94% compared with 6% to 81%), and < 2.5 mmol/l (< 97 mg/dl) (47% to 69% compared with 0 to 53%), respectively. Results favoring rosuvastatin versus the comparators were also reported for patients: (a) who had triglycerides > or = 200mg/dl (> or = 2.3 mmol/l), and achieved both ATP III LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) goals (80% to 84% versus 15% to 84%); (b) overall who achieved the Canadian LDL-C goals of < 2.5 (< 97 mg/dl) to < 5.0 mmol/l (< 193 mg/dl) (85% to 91% versus 44% to 86%); and (c) who achieved all 3 Canadian goals for LDL-C, triglycerides (< 3.0 mmol/l [< 266 mg/dl] to < 2.0 mmol/l [< 177 mg/dl]), and the total cholesterol/high-density lipoproteincholesterol ratio (< 4 to < 7) (70% to 83% versus 35% to 79%).     

Atorvastatin: pharmacological characteristics and lipid-lowering effects

By inhibiting 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, the statins reduce hepatocyte cholesterol levels, which results in up-regulation of low-density lipoprotein (LDL) receptors and, consequently, increased clearance of LDL-cholesterol (LDL-C) from the plasma. Structural differences among the available statins partially account for differences in their capacity to inhibit HMG-CoA reductase and their lipid-lowering efficacy, and for variability in other biological properties, such as their pharmacokinetic characteristics and their tolerability and propensity to interact with other drugs. In terms of pharmacokinetic properties, the synthetic (type II) HMG-CoA analogue atorvastatin exhibits a number of characteristics that are different to those of other members of the class, including a longer plasma half-life and metabolites that have an ability to inhibit HMG-CoA reductase equivalent to that of the parent drug. These characteristics are postulated to be responsible for a more prolonged inhibition of HMG-CoA reductase, and, hence, for the greater efficacy of atorvastatin in decreasing total and LDL-C levels relative to other statins (with the exception of rosuvastatin) noted in clinical trials in patients with dyslipidaemias. From the available clinical trial data, atorvastatin can be considered one of the most effective statins, not only by taking into account its effects on LDL-C and ability to meet recommended treatment guidelines for this parameter, but also its effect on triglyceride levels and capacity to modify lipoprotein composition in a non-atherogenic manner. Clinical studies with atorvastatin have also shed some light on the question as to whether it is better to focus on obtaining maximal reduction of LDL-C in at-risk patients or on cardiovascular outcomes. Cardiovascular event rates have been shown to be substantially lower in patients attaining LDL-C levels between 1.0 and 1.6 mmol/L (40-60 mg/dL) or < or =1.0 mmol/L (< or =40 mg/dL) compared with higher levels (>2.1-2.6 mmol/L [>80-100 mg/dL]). This finding reinforces the update of the National Cholesterol Education Programme's clinical practice guidelines, which recommend LDL-C levels <2.6 mmol/L (100 mg/dL) to be the goal of antihyperlipidaemic drug therapy in high-risk patients with CHD, with an optional therapeutic target of <1.8 mmol/L (70 mg/dL) in patients at very high risk.     

Effect of rosuvastatin compared with other statins on lipid levels and National Cholesterol Education Program goal attainment for low-density lipoprotein cholesterol in a usual care setting

STUDY OBJECTIVE: To compare, in a usual care setting, the effects of rosuvastatin and other 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) on lipid levels and on goal attainment of low-density lipoprotein cholesterol (LDL) levels from the National Cholesterol Education Program (NCEP) third report of the Adult Treatment Panel (ATP III). DESIGN: Retrospective, longitudinal, cohort study. DATA SOURCE: Managed care medical and pharmacy claims and laboratory database. PATIENTS: A total of 8251 patients starting treatment with rosuvastatin, atorvastatin, simvastatin, pravastatin, lovastatin, or fluvastatin from August 1, 2003-September 30, 2004, excluding those who received dyslipidemic therapy in the previous 12 months. MEASUREMENTS AND MAIN RESULTS: Patients with at least one pretreatment and posttreatment lipid level were followed until their initial statin was changed or they reached the end of benefit eligibility or the study period. Percent changes in lipid levels were calculated, and adjusted changes in LDL and goal attainment were evaluated by regression techniques. Absolute and percent reductions in LDL, triglyceride, and total cholesterol levels were significantly greater with rosuvastatin than with other statins (all p<0.05 except for triglyceride reduction vs atorvastatin). After adjustment for age, sex, and baseline LDL, percent LDL reductions still were significantly greater with rosuvastatin than with other statins (p<0.05). Changes in high-density lipoprotein cholesterol were not significant. Goal attainment was higher with rosuvastatin than with other statins after adjustment for age, sex, baseline LDL, risk status, dose, and duration of therapy (p<0.05). Dose-stratified analysis showed that LDL goal attainment was significantly higher with rosuvastatin 10 mg than with atorvastatin 10 or 20 mg. CONCLUSION: Rosuvastatin was more effective than other statins in reducing LDL, triglyceride (except vs atorvastatin), and total cholesterol levels. Significantly more patients taking rosuvastatin than patients taking other statins attained their LDL goals.