Efficacy of atorvastatin after LDL-cholesterol-based dose selection in high risk dyslipidaemic patients: results of the target dose study

ABSTRACT

Background: Hypercholesterolaemia is one of the major risk factors for the development of coronary heart disease (CHD). European guidelines emphasize the importance of reducing low-density lipoprotein cholesterol (LDL?C) levels below 115?mg/dL (3.0?mmol/L) in patients with high CHD risk.

Objective: The present study evaluates whether selection of the atorvastatin starting dose based on baseline LDL?C levels and previous statin treatment status would result in an achievement of LDL?C targets without the need for up-titration.

Methods: A multicentre, prospective, open-label study conducted in Belgium. Patients were at high risk defined as either a history of CHD, another atherosclerotic disease, diabetes mellitus Type 2 or an estimated 10?year CHD risk > 20%. The primary endpoint was the proportion of patients achieving the LDL?C goal after 12 weeks of treatment.

Results: Overall, 96.4% of the 195 statin-naïve patients reached the LDL?C target after 12 weeks of treatment. The majority of the patients (95.4%) already reached LDL?C control at Week 6. Mean (SD) LDL?C levels decreased from 159 (25)?mg/dL[(4.1 (0.6)?mmol/L] to 86 (14)?mg/dL [2.2 (0.4)?mmol/L] after 12 weeks of treatment. Only 4.6% of the patients needed an up-titration at Week 6.

Conclusions: Taken together, the results demonstrate that LDL?C based dose selection of atorvastatin is highly efficacious for rapid achievement of target LDL?C levels with a low need for up-titration. Application of this flexible first dosing strategy in general practice will, based on available evidence, increase adherence to atorvastatin treatment in patients with high CHD risk.     

The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin: results of the EASEGO study

ABSTRACT

Objective: To assess the incremental low-density lipoprotein-cholesterol (LDL-C) lowering efficacy of doubling the statin dose or switching to the ezetimibe/simvastatin 10/20?mg combination tablet (EZE/SIMVA) in patients on simvastatin 20?mg or atorvastatin 10?mg not at LDL-C target < 2.5?mmol/L.

Study design and methods: Patients with documented coronary heart disease (CHD) and/or type 2 diabetes (DM2) with LDL-C ≥ 2.5 and < 5.0?mmol/L despite treatment with atorvastatin 10?mg or simvastatin 20?mg were randomized to (1) double statin dose or (2) switch to ezetimibe/simvastatin 10/20, according to a PROBE study design. LDL-C, lipoprotein subfractions and safety data were assessed during the study.

Results: 119 of 178 (67%) patients in the EZE/SIMVA group and 49 of 189 (26%) in the doubling statin group reached target LDL-C < 2.5?mmol/L. The odds ratio of success for EZE/SIMVA versus doubling statin treatment in reaching the LDL-C target of < 2.5?mmol/L was 5.7 (95% CI: 3.7–9.0, p < 0.0001). A reduction in total cholesterol (TC), total/high density lipoprotein (HDL) cholesterol ratio and apolipoprotein B was observed in both groups, but this reduction was significantly more pronounced in the EZE/SIMVA group as compared with the doubling statin dose group. Treatment was well tolerated and no difference was observed between the two groups with regard to adverse effects.

Conclusions: In CHD/DM2 patients treated with simvastatin or atorvastatin with LDL-C persistently ≥ 2.5?mmol/L, switching to the EZE/SIMVA was more effective in attaining the LDL-C target of < 2.5?mmol/L than doubling the statin dose.     

Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome

SUMMARY

Objective: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS).

Research design and methods: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10?mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) ≥ 150?mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40?mg/dL (1.04 mmol/L) for men or < 50?mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) ≥ 110?mg/dL (≥ 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure ≥ 130/ ≥ 85 mmHg; waist circumference > 88?cm (women) or > 102?cm (men). DM patients were excluded from the MetS subgroup analysis.

Main outcome measures: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study.

Results: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals (?p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups.

Conclusions: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS.     

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

ABSTRACT

Objective: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity.

Methods: We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study – RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40–80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL?C) < 1.0?mmol/L (< 40?mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10?mg or atorvastatin 20?mg daily 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 daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks.

Results: After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39?U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84?U/L, p = 0.77). The difference between groups did not reach significance (?p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (?p = 0.0001) and similar increases in HDL?C after 6 weeks [0.06?mmol/L (2.32?mg/dL) vs. 0.05?mmol/L (1.93?mg/dL)] and after 18 weeks [0.10?mmol/L (3.87?mg/dL) vs. 0.10?mmol/L (3.87?mg/dL)].

Conclusions: Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin.     

Treating to target patients with primary hyperlipidaemia:comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study)

ABSTRACT

Objectives: In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular diseasefree subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL).

Methods: After a 6‐week dietary lead-in period, patients were randomized to RSV 10?mg/day (?n = 60) or ATV 20?mg/day (?n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20?mg/day or ATV 40?mg/day) if the treatment goal was not achieved. A control group of healthy volunteers (?n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL‐C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters.

Results: A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL‐C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C‐reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL‐C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect.

Conclusions: RSV and ATV were equally efficacious in achieving LDL‐C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL‐C-raising effect, while ATV lowers serum uric acid levels.     

Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin

ABSTRACT

Background: Recent guidelines underline the need for high-risk patients to reach strict low density lipoprotein cholesterol (LDL?C) targets (1.8–2.6?mmol/L; 70–100?mg/dL), and specifically mention the possible use of combination therapy (e.g. statin + ezetimibe) to achieve these goals.

Methods: A retrospective case-note audit was carried out to assess the response to administering ezetimibe in patients unable to tolerate statins (Group 1), or high dose of statins (Group 2) and patients who cannot achieve the LDL?C target (2.6?mmol/L; 100?mg/dL) despite taking a statin (Group 3).

Results: Ezetimibe lowered LDL?C levels by 20–29% across the 3 patient groups after 2–3 months of treatment. High density lipoprotein cholesterol (HDL?C) levels tended to remain unchanged, although there was a consistent trend for a fall if baseline values were ‘high’. However, the LDL-C/HDL-C ratio changed significantly and favourably in all groups. The fall in fasting triglyceride levels in all groups was greater (reaching 19–25%) when baseline levels were ≥ 1.5 or 1.7?mmol/L (136–150?mg/dL). There were no marked abnormalities in liver function tests or creatine kinase activity. In Group 3 there was a significant trend for a fall in serum creatinine levels across the tertiles of baseline creatinine values.

Limitations of the present study include the small sample size (especially in Groups 1 and 2), its short-term duration and the absence of event-based end-points. Therefore, the results are hypothesis-generating rather than conclusive.

Conclusions: When used alone or added to a statin, ezetimibe favourably altered the LDL?C/HDL?C ratio and lowered triglyceride levels. Ezetimibe was well tolerated in patients with statin intolerance and was associated with a 26% fall in LDL?C. An additional action may be some degree of improved renal function. Further studies are needed to confirm these findings.     

Attaining United Kingdom-European Atherosclerosis Society Low-density Lipoprotein Cholesterol Guideline Target Values in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study

Summary

The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study compared two standards (structured vs. usual care) of lipid lowering treatment in 1600 patients with coronary heart disease (CHD). Structured care aimed at achieving (with atorvastatin 10-80?mg) the low-density lipoprotein cholesterol (LDL-C) (2.6?mmol/l; 100?mg/dl) goal described in the NCEP ATP II and III guidelines for patients with CHD. Structured care was associated with a significant reduction in overall mortality and coronary events compared to usual care.

In the present brief report we interpret the results of GREACE using the United Kingdom (UK) and European Atherosclerosis Society (EAS) treatment goal for LDL-C in secondary CHD prevention (3.0?mmol/l; 115?mg/dl). The mean dose of atorvastatin decreased from 24?mg to 22?mg/day. More patients achieved the UK and EAS LDL-C target (95.6 vs. 95%) in the structured care arm of the trial; 90% of the patients achieved this target with 10 or 20?mg atorvastatin.

These findings may have cost implications, especially if the LDL-C target for high-risk patients will fall below those described above.     

Effect of atorvastatin on highdensity lipoprotein cholesteroland its relationship withcoronary events: a subgroupanalysis of the GREekAtorvastatin and Coronary-heart-disease Evaluation (GREACE) Study

SUMMARY

Objective: To investigate the relationship between changes in high density lipoprotein cholesterol (HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration

with atorvastatin (10-80mg/day, mean 24mg/day) achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care.

Methods: Analysis of variance was used to assess the effect of atorvastatin on HDL-C over

time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model, involving backward stepwise logistic regression, was used to evaluate the relation between coronary events and HDL-C changes.

Results: The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p?=?0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterol-aemia; p?=?0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p?=?0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence

interval 0.76-0.94; p?=?0.002) for every 4?mg/dL (0.1?mmol/L) increase in HDL-C.

Conclusions: There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase. This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C) reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.     

Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study

SUMMARY

Background: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100?mg/dL (2.6?mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. This study demonstrated significant reductions in morbidity and mortality associated with active dose titration of atorvastatin and structured management of dyslipidaemia.

Methods and results: Intention-to-treat analysis (Cox proportional hazards model)?was used to assess the relationship between lipid values and coronary events. Higher levels of LDL-C at baseline were associated with a greater risk of subsequent events among patients randomized to usual care. Reducing the LDL-C and the non-high density lipoprotein cholesterol (non-HDL-C) level to the National Cholesterol Educational Program (NCEP) Adult Treatment Panel (ATP) III goals required greater doses of atorvastatin for the higher baseline quartile of LDL-C. During the study there was a greater reduction in the risk of coronary heart disease (CHD) events in atorvastatin-treated patients who were in the highest quartile of LDL-C at baseline, after achieving the LDL-C treatment goal, in comparison to the usual care patients in the highest baseline LDL-C quartile.

Conclusions: Achieving the NCEP ATP III LDL-C and non-HDL-C goals by titrating up the dose of atorvastatin was associated with a significant reduction in vascular events in patients with CHD. The greatest benefit was seen in those patients with the highest baseline LDL-C levels.     

Dual cholesterol inhibition with ezetimibe/simvastatin in pre-treated hypercholesterolaemic patients with coronary heart disease or diabetes mellitus: prospective observational cohort studies in clinical practice

ABSTRACT

Objective: Patients with primary hypercholesterolaemia and concomitant coronary heart disease (CHD) and/or diabetes mellitus (DM), who are at particularly high risk of cardiovascular events such as stroke or myocardial infarction, benefit from aggressive lipid lowering strategies. The present studies investigated the incremental efficacy and safety of dual cholesterol inhibition with ezetimibe/simvastatin in such high-risk patients pre-treated with statins but not reaching the 100?mg/dL (2.6?mmol/L) low density cholesterol (LDL?C) cholesterol threshold in the primary care setting.

Methods: Two open-label, prospective, non-random­ised, observational studies (study 1 with n = 19?194 patients, predominantly with CHD; study 2 with n = 19?484 patients, predominantly with DM). Patients received – almost all after statin pre-treatment – ezetimibe 10?mg plus simvastatin 10?mg (study 1: 15%, study 2: 16%), 20?mg (in 68% each), 40?mg (12%/10%) or 80?mg (1%/1%) as fixed dose combinations over 3 months (dosage at investigator's discretion).

Results: Mean LDL-C was reduced by 28%/27% (study 1/ study 2) compared with baseline values (on statin monotherapy). Mean total cholesterol was decreased by 22% in each study, mean triglycerides by 16/17%, and mean high density cholesterol (HDL?C) was increased by 9/10%. Adverse events were reported in 0.3% and 0.2% of patients, respectively.

Conclusion: Dual cholesterol inhibition with ezetimibe/simvastatin was effective and well tolerated under real practice conditions in high-risk patients with CHD and/or DM.     

Effectiveness of simvastatin therapy in raising HDL-C in patients with type 2 diabetes and low HDL-C

SUMMARY

Objective: To evaluate the efficacy of high and moderate doses of simvastatin (80 and 40?mg), for raising high density lipoprotein-cholesterol (HDL-C), improving HDL sub-fractions, and affecting other parameters, including high sensitivity C-reactive protein (hs-CRP), in patients with type 2 diabetes mellitus (DM) and low HDL-C.

Research design and methods: This double-blind, placebo-controlled, randomized, 3-period, complete block, 6-week crossover study examined the efficacy of simvastatin in adult men and women (N = 151) with stable type 2 DM (HbA_1C < 9%), low density lipoprotein-cholesterol (LDL-C) > 100?mg/dL (2.6?mmol/L), HDL-C < 40?mg/dL (< 1?mmol/L), and fasting triglyceride level > 150 (> 1.7?mmol/L) and < 700?mg/dL (< 7.9?mmol/L). This study included adult men (71%) and women (29%) of various races (89% white, 6% black, 1% Asian, 3% other) enrolled from 29 practice-based sites in the United States.

Main outcome measures: Percentage change in HDL-C from baseline at the end of each 6-week treatment interval.

Results: Both simvastatin 80 and 40?mg significantly increased total HDL-C from baseline (mean increases of 8% ± 1 [SE] and 5% ± 1, respectively; p < 0.001) compared with placebo, and significantly reduced plasma concentrations of LDL-C (?p < 0.001), triglycerides (?p < 0.001), apolipoprotein B (?p < 0.001), and hs-CRP (?p ≤ 0.012). Compared with simvastatin 40?mg, the 80?mg dose provided additional efficacy. Simvastatin 80?mg also significantly (?p < 0.001) increased HDL₂ from baseline (14% ± 3[SE]) and placebo phases (10 ± 3). An exploratory analysis showed 87% (simvastatin 80?mg) and 82% (simvastatin 40?mg) of patients reached the NCEP ATP III treatment goals for LDL-C compared with 14% on placebo.

Conclusions: Both simvastatin 80 and 40?mg raise HDL-C and improve other measures associated with elevated coronary risk in patients with type 2 DM and low HDL-C.     

Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe

ABSTRACT

Lowering serum cholesterol levels reduces the risk of coronary heart disease (CHD)-related events. Statins are commonly prescribed as first-line treatment but many patients at high-risk for CHD still fail to reach their cholesterol or low-density lipoprotein cholesterol (LDL-C) goals with statin monotherapy.

National and international guidelines for the prevention of CHD recommend the modification of lipid profiles and particularly LDL‐C [e.g. the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III; 2001) and Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (2003) Guidelines]. Several recent clinical trials indicated an added benefit from aggressive lowering of LDL‐C levels. Based on these findings, the NCEP ATP III revised the LDL‐C target from < 100?mg/dL (2.6?mmol/L) to < 70?mg/dL (1.8?mmol/L) (optional target) for very high-risk patients and < 130?mg/dL (3.4?mmol/L) to < 100?mg/dL (2.6?mmol/L) for moderately high-risk patients.

For patients who fail to achieve their LDL‐C target, inhibiting the two main sources of cholesterol – synthesis and uptake – can produce more effective lipid lowering, allowing more patients to reach their LDL‐C goal. Ezetimibe is a highly-selective inhibitor of cholesterol absorption and simvastatin is an evidence-based inhibitor of cholesterol synthesis. The LDL‐C-lowering efficacy of targeting both major sources of cholesterol with ezetimibe plus simvastatin was demonstrated in several multicentre, double-blind, placebo-controlled trials in patients with hypercholesterolaemia. For patients who do not reach their cholesterol goal with a statin, adding ezetimibe 10?mg significantly reduces LDL‐C compared with statin monotherapy. Thus, this treatment option may help patients reach the new ‘stricter’ cholesterol goals.

This review, based on a Medline database search from January 2000 to August 2005, considers the LDL‐C-lowering efficacy of ezetimibe and discusses the role of this agent for patients who fail to achieve guideline cholesterol goals with statin monotherapy.     

LDL cholesterol levels after switch from atorvastatin to rosuvastatin

Objective: Initial statin therapy may not always adequately reduce elevated low-density lipoprotein cholesterol (LDL-C) levels. Although alternative therapies are available, switching to another statin may be beneficial, especially for those at highest risk of cardiovascular disease and events. This study examined changes in LDL-C levels following a switch from 40/80?mg of atorvastatin (ATV) to 20/40?mg of rosuvastatin (RSV).

Methods: This retrospective cohort study used data from the MarketScan administrative claims databases linked to laboratory values. Patients with or at risk for atherosclerotic cardiovascular disease (ASCVD) who switched from ATV 40/80?mg to RSV 20/40?mg and had LDL-C values measured within 90 days before and 30–180 days after the switch were included. The change in LDL-C was quantified for each patient and summarized across all patients and within each switch pattern (e.g. ATV40 to RSV20).

Results: There was a significant mean (SD) decrease in LDL-C of 21% (30%) across the whole sample (N?=?136) after switching from ATV to RSV. The greatest decrease occurred in patients who switched from ATV40 to RSV40 (N?=?20; ?29% [19%]; p?N?=?112; ?24% [24%]; p?Conclusions: Switching from ATV to RSV was associated with a significant decrease in LDL-C among high-risk patients. Switching between these two high-intensity statins may offer a viable alternative to other treatment modifications aimed at lowering LDL-C in this population.     

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.     

Treatment with Atorvastatin to the National Cholesterol Educational Program Goal Versus 'Usual' Care in Secondary Coronary Heart Disease Prevention

Summary

Background: Atorvastatin is very effective in reducing plasma low-density lipoprotein cholesterol (LDL-C) levels. However, there is no long-term survival study that evaluated this statin.

Patients?Methods: To assess the effect of atorvastatin on morbidity and mortality (total and coronary) of patients with established coronary heart disease (CHD), 1600 consecutive patients were randomised either to atorvastatin or to 'usual' medical care. The dose of atorvastatin was titrated from 10 to 80mg/day, in order to reach the National Cholesterol Education Program (NCEP) goal of LDL-C <100mg/dl (2.6mmol/l). All patients were followed up for a mean period of 3 years.

Main Outcome Measures: Primary endpoints of the study were defined as death, non-fatal myocardial infarction, unstable angina, congestive heart failure, revascularisation (coronary morbidity) and stroke. Secondary endpoints were the safety and efficacy of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin.

Results: The mean dosage of atorvastatin was 24?mg/day. This statin reduced total cholesterol by 36%, LDL-C by 46%, triglycerides by 31%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 44%, while it increased HDL-C by 7%; all these changes were significant. The NCEP LDL-C and non-HDL-C treatment goals were reached by 95% (n?=?759) and 97% (n?=?776), respectively, of patients on atorvastatin. Only 14% of the 'usual' care patients received any hypolipidaemic drugs throughout the study and 3% of them reached the NCEP LDL-C treatment goal. The cost per quality-adjusted life-year gained with atorvastatin was estimated at $US 8350. During this study 196 (24.5%) CHD patients on 'usual' care had a CHD recurrent event or died vs. 96 (12%) CHD patients on atorvastatin; risk ratio (RR) 0.49, confidence interval (CI) 0.27-0.73, p?<?0.0001. In detail, atorvastatin reduced, in comparison to 'usual' care, total mortality (RR 0.57, CI 0.39-0.78, p?=?0.0021), coronary mortality (RR 0.53, CI 0.29-0.74, p?=?0.0017), coronary morbidity (RR 0.46, CI 0.25-0.71, p?<?0.0001), and stroke (RR 0.53, CI 0.30-0.82, p?=?0.034). All subgroups of patients (women, those with diabetes mellitus, arterial hypertension, age 60 to 75 years, congestive heart failure, recent unstable angina or prior revascularisation) benefited from treatment with atorvastatin. Withdrawal of patients because of side-effects from the atorvastatin group was low (0.75%) and similar to that of the 'usual' care group (0.4%).

Conclusions: Long-term treatment of CHD patients with atorvastatin to achieve NCEP lipid targets significantly reduces total and coronary mortality, coronary morbidity and stroke, in comparison to patients receiving 'usual' medical care. Treatment with atorvastatin is well tolerated and cost-effective.     

Effects of Low-Dose Atorvastatin and Rosuvastatin on Plasma Lipid Profiles

BACKGROUND AND OBJECTIVE: Despite the favorable effects of reduction of low-density lipoprotein-cholesterol (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia. METHODS: In this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks. RESULTS: At 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (-44.32% vs -30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used. CONCLUSION: In high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.