James M. McKenney, PharmD

: To understand the practice patterns and National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal attainment rates after switching patients from simvastatin (SMV) to other statins or the combination of SMV and ezetimibe (EZE).

: This retrospective study linked claims and laboratory data from a national health plan. Patients were included if they were taking SMV and were switched to other statins or a fixed-dose combination of SMV and EZE between July 1, 2005, and June 30, 2006. Patients taking dual SMV/EZE before switch were excluded from the study.The NCEP ATP III risk status of patients at switch was assessed based on medical claims, pharmacy claims, and laboratory values in the 12-month preswitch period. Lipid data (available on a patient subset) were used to estimate patientsâ€™ goal attainment status at and after switch.

: Of 134 168 patients taking SMV, 11 929 (8.9%) switched to other statins or SMV/EZE. The mean age of switching patients was 54 years (standard deviation, 9 years), 61% were men, 50% were high risk, and 30% were moderate risk. The mean time to switch among new starters of SMV (n = 3379) was 77 days. Forty percent (n = 4772) of the total switches occurred among those taking the lower doses (5, 10, and 20 mg) of SMV. Most patients switched from SMV to SMV/EZE (60.5%), followed by atorvastatin (17.3%), rosuvastatin (10.1%), lovastatin (8.6%), pravastatin (2.9%), and fluvastatin (0.7%). Similarly, most patients switching from higher doses of SMV switched to SMV/EZE (52.5%), followed by atorrestatin (21.1%) and rosuvastatin (10.1%). Overall, 55.6% (758 of 1362) of patients were at ATP III goal at the time of switch from SMV (across all doses; n = 758), and 56.1% (292 of 521) of those taking lower doses were at goal at time of switch. A majority (69.9%) of patients who were at goal and switched from SMV (across all doses) were switched to SMV/EZE, and 61.6% of those at lower doses of SMV switched to the combination drug. Of patients who were not at goal at switch (n = 604), 73.3% attained ATP III LDL-C goal after switch. The mean percent LDL-C reduction that was needed to attain LDL-C goal at switch from SMV (n = 604) was 18.1%. 

: There is an opportunity to further increase LDL-C goal attainment rates among patients switched from SMV. The clinical, prescription benefit design, and economic implications of the finding that a majority of patients are at goal when switched from SMV and a majority of patients are being switched from SMV to SMV/EZE need to be further examined.

In conjunction with diet and exercise, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors (statins) are the recommended therapy for reducing low-density lipoprotein cholesterol (LDL-C) and are the most widely used agents in the treatment of dyslipidemia.

 Several statins have been extensively studied and have been shown to reduce cardiovascular morbidity and mortality.

 Although no cardiovascular morbidity or mortality data with rosuvastatin are currently available, clinical studies examining the impact of rosuvastatin on cardiovascular events and mortality are currently being conducted.

 Similarly, the effects of ezetimibe given either alone or in addition to an HMG-CoA reductase inhibitor or fenofibrate on cardiovascular morbidity and mortality have not yet been established.

A significant development in the statin marketplace in 2006 was the availability of a generic form of simvastatin (SMV), with the first generic version approved in June 2006.

 This has afforded a significant opportunity to clinicians and payers to provide effective and efficient dyslipidemia care for the appropriate patient groups.

 To deliver quality care with the effective use of resources, it is important to understand the pattern of switching patients from SMV to other statin therapies including a fixed-dose combination of SMV and ezetimibe (EZE). In addition, it will also be valuable in further understanding the rationale and the effectiveness of switching in terms of National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III goal attainment criteria. The aim of the present study was to evaluate patterns of switching from SMV and NCEP ATP III goal attainment rates among switched patients in a large national health plan enrollee population.

. This retrospective analysis linked medical claims, pharmacy claims, enrollment information, and laboratory data from a large national health plan. The claims data were submitted by physicians, facilities, and pharmacies for payment of services provided to covered commercial, Medicare Advantage, and Medicaid health plan members. The database includes approximately 14 million covered lives annually with both medical and pharmacy coverage. Data were de-identified and met the requirements for the protection of private health information in accordance with the Health Insurance Portability and Accountability Act of 1996.

. All patients aged 18 years or older with a dispensing (ie, prescription fill) for SMV between July 1, 2005 and June 30, 2006 were identified. Switchers were defined as those patients prescribed another statin or a fixed-dose combination of SMV/EZE during the same period after a monotherapy SMV dispensing. Patients taking dual SMV/EZE therapy before the switch were excluded from the study sample. Variable follow-up observation was permitted until disenrollment. Patients were considered new users of SMV if they had no prior use of SMV within a year; continuing users were those for whom no gap in therapy during the 12-month baseline period was observed. The subsets of patients with qualifying LDL-C laboratory results in both the preswitch and postswitch periods were identified for the analysis of NCEP ATP III goal attainment. The baseline LDL-C value was defined as the LDL-C value within 6 months before switch. The follow-up LDL-C value was defined as LDL-C value after 30 days of switch. If multiple LDL-C values were available in each baseline and postswitch periods, then an average LDL-C value was estimated.

. In accordance with NCEP ATP III guidelines,

 patients were classified into risk categories. The presence of risk factors was determined from diagnoses on medical claims, filled prescriptions on pharmacy claims, and cholesterol laboratory results in the 6-month preindex period. Each risk factor was identified and patients were categorized into risk groups based on the number and combination of risk factors present. The highrisk group included those with administrative data codes for myocardial infarction, ischemic heart disease, cerebral vascular accident, transient ischemic attack, coronary artery bypass graft, angioplasty, peripheral vascular disease, or diabetes. High-risk patients had a target LDL-C goal of <100 mg/dL. Moderate risk was defined as the presence of at least 2 of the following 3 risk factors: hypertension (

International Classification of Diseases, Ninth Revision code and pharmacy claim for antihypertensive agents

), age (men of ages ≥45 years and women of ages ≥55 years), or preindex high-density lipoprotein cholesterol <40 mg/dL. Patients in the moderate-risk group had a target LDL-C goal of <130 mg/dL. Patients in the low-risk group (<2 risk factors) were assigned a target LDL-C goal of <160 mg/dL. Because the NCEP-defined risk factors of smoking status and family history of premature coronary heart disease (CHD) cannot be obtained accurately from administrative claims, these risk factors were not included in the risk  tratification process. Similarly, the Framingham risk score could not be computed based on available data.

. This was a descriptive analysis to explore the pattern of switching and NCEP ATP III goal attainment status among patients treated with SMV. The switching patterns from SMV to other statins or SMV/EZE and by SMV dose were determined. The percentage of patients who were at NCEP goal at the time of switch from SMV, as well as the percentage of patients who attained NCEP goal after switching from SMV, were also estimated.

Patient Characteristics. Of the approximately 14 million enrollees with data contained in the research database during the period from July 1, 2005 through June 30, 2006, a total of 134 168 patients had a dispensing for SMV. A total of 11 929 (8.89%) patients switched to another statin during this same period (

). The mean age of patients was 53.79 years (standard deviation, 8.65 years), and 61% were men (

). Fifty percent of patients switching from SMV to another statin were at high risk for CHD, 20% were at moderate risk, and 30% were at low risk (Table 1). Most patients were prescribed a 20-mg (34.31%) or 40- mg (46.62%) dose of SMV before switching. Patient characteristics were similar between the full sample and the subsample with LDL-C results (Table 1).

. As shown in Table 2, the most common switch from SMV (n = 11 929) was to SMV/EZE (60.54%), followed by atorvastatin (17.26%), rosuvastatin (10.05%), and lovastatin (8.60%). Only a small percentage of patients (3.55%) switched to pravastatin or fluvastatin. Of the total patients switched, 40% were switched from a low-dose (5, 10, or 20 mg) SMV. At every dose of SMV, patients were most likely to switch to SMV/EZE (46.43% at 5 mg; 47.67% at 10 mg; 53.26% at 20 mg; 65.11% at 40 mg; and 68.80% at 80 mg SMV). Fifty-two percent (2503 of 4772) of patients switched from low doses of SMV to SMV/EZE. Of these 2503 patients who switched from low-dose SMV to SMV/EZE, 8.35% were switched to 10-mg EZE/10-mg SMV, 60.41% were switched to 10-mg EZE/20-mg SMV formulation, 29.44% switched to 10-mg EZE/40-mg SMV, and 1.80% switched to 10-mg EZE/80-mg SMV formulation.

Switching by LDL-C Goal Status Before Switch

. A total of 1362 switching patients (of the total 11 929 SMV switchers, 11.42%) had available baseline and follow-up LDL-C results. At the time of the switch, 55.65% of these patients (n = 758) were at NCEP ATP III goal. Forty-six percent of patients who were at goal at the time of switch were considered to be at low risk for CHD, 19.92% were at moderate risk, and 34.30% were at high risk. Among patients not at goal at time of switch (n = 604), 14.40% were at low risk, 17.22% were at moderate risk, and 68.38% were at high risk. Of SMV users already at goal before switching therapy, close to 70% switched to SMV/EZE, 13% switched to atorvastatin, and 7.92% to rosuvastatin (Figure 2, Table 3). Similarly, 67% of patients not at goal at switch switched to SMV/EZE, 15.56% switched to atorvastatin, and 8.28% switched to rosuvastatin (

. Of patients who were not at goal at switch, the mean percent reduction in LDL-C needed to attain NCEP goal at time of switch was 18.06%. Of these patients, 73.34% attained NCEP goal after switch. Among these patients (not at goal at time of switch and then achieving goal after switch), a mean percent reduction required at time of switch was 15.72%, whereas those not at goal after switch required a 24.50% reduction to reach goal.

In this study, 9% of SMV users switched to another statin in the course of a 1-year observation time frame. For health plans and clinicians aiming to achieve efficient and effective management of dyslipidemia, this highlights a need to better understand the patterns and clinical outcomes of switching patients from SMV to other alternatives. This study provides a descriptive summary of the trends in switching from SMV and the associated goal attainment outcomes.

In the present study, across all SMV doses, the most common switch from SMV was to SMV/EZE. In addition, of the patients switched from lower doses (5, 10, and 20 mg) of SMV, a large majority of them switched to SMV/EZE. Although it was not possible to determine the reasons for the switch, this is an interesting finding and indicates the need to determine the reason why patients were switched from a low dose of SMV to a combination of SMV and EZE as opposed to titrating to a higher dose of SMV. If tolerability to SMV was a reason behind the switch, then it makes clinical sense to switch to a non-SMV statin (eg, atorvastatin or rosuvastatin). However, it was observed that quite a few switches from lower doses of SMV were to SMV/EZE combinations without trying higher doses of SMV (including the 40-mg dose). Switches from lower doses of SMV to atorvastatin (21.12%) or rosuvastatin (10.05%) were also observed but to a much lesser extent compared with switches to SMV/EZE. Individual health plans and providers may have an interest in understanding the rationale for switching from lower doses of SMV to SMV/EZE combination, as well as evaluating the potential quality of care and economic consequences of switching from SMV in their local setting.

The study period only allowed switching pattern observation during the time period in which branded SMV was available. Future research should examine if the observed SMV switching patterns and trends change significantly with the availability of generic forms of SMV.

The analysis indicated that more than half of switching patients had already attained NCEP ATP III LDL-C goal at the time of switch. One of the potential reasons for switching patients who were already at goal could be adoption of more aggressive LDL-C targets11 by clinicians or tolerability issues with SMV. It is important to further determine the actual rationale behind switching these patients. The findings indicate that close to 70% of the patients who were already at goal at baseline were switched to SMV/EZE. Understanding the clinical rationale and clinical and economic implications of switching these at-goal patients from SMV to SMV/EZE may be important to providers in meeting their goal of providing effective and efficient management of dyslipidemia.

The study results highlight an opportunity to further increase LDL-C goal attainment rates among patients switched from SMV. Of those patients not at goal at switch, 73% of patients attained NCEP ATP III goal after switching to another agent. This may indicate that more effective treatment strategies (including more effective combination treatment strategies) may help to further improve the rate of goal attainment in these patients. Due to limited sample size, a comparison of individual statin-specific goal attainment rates after switch from SMV could not be estimated and this highlights further areas of research.

2. Gould AL, Rossouw JE, Santanello NC, et al

. Cholesterol reduction yields clinical benefit: impact of statin trials. 

 Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. 

6. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group

. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. 

8. Serruys PW, de Feyter P, Macaya C, et al

. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. 

10. Downs JR, Clearfield M, Weis S, et al.

 Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. 

. Investigating cardiovascular risk reductionâ€”the Rosuvastatin GALAXY Programme. 

. FDA news release: FDA approves first generic simvastatin. June 23, 2006 [updated July 5, 2006]. Available at: 

http://www.fda.gov/bbs/topics/NEWS/2006/NEW01394.html

. Comparative effectiveness of rosuvastatin versus other statin therapies in patients at increased risk of failure to achieve low-density lipoprotein goals. 

17. US Department of Health & Human Services Office for Civil Rights

. HIPAA: Medical Privacyâ€”National Standards to Protect the Privacy of Personal Health Information. Last modified May 16, 2006. Available at: 

http://www.hhs.gov/ocr/hipaa/finalreg.html

Articles

Understanding Practice Patterns and Low-density Lipoprotein Cholesterol Goal Attainment Implications of Switching Patients From Simvastatin in a Health Plan Setting

: Assessments of the effectiveness and cost-effectiveness of treatment with statins in high-risk patients in routine clinical practice are needed. The objective of the present study was to estimate the clinical effectiveness and cost-effectiveness of rosuvastatin compared with atorvastatin or simvastatin among high-risk patients as treated in routine clinical practice.

: Patients aged 18 to 79 years with coronary heart disease (CHD) or equivalent who initiated treatment with atorvastatin, rosuvastatin, or simvastatin were included. Primary outcome variables were the percent reduction in low-density lipoprotein cholesterol (LDL-C), achievement of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal, treatment costs, and cost-effectiveness. Regression models were used to adjust outcome measures for age, sex, CHD, baseline LDL-C, and therapy duration. A decision analytic model was used to assess incremental cost-effectiveness. 

: Of the 775 eligible patients, rosuvastatin patients had higher baseline LDL-C levels (156 mg/dL vs 142 mg/dL or 137 mg/dL, respectively) compared with atorvastatin or simvastatin. Adjusted for baseline factors, percent LDL-C reduction was significantly greater with rosuvastatin versus atorvastatin or simvastatin (37% vs 28% or 27%, respectively; 

 <.05). The estimated percentage of patients attaining NCEP ATP III goal was higher (

 <.05) for rosuvastatin (69.7%) compared with atorvastatin (54.8%) or simvastatin (51.2%), adjusted for baseline characteristics. Rosuvastatin patients also had the lowest annualized treatment costs ($934 vs $1050 or $1545 for atorvastatin or simvastatin). Rosuvastatin was more effective and less costly than atorvastatin and at current branded and generic prices of simvastatin. A 60% to 68% discount from simvastatin branded price was needed to achieve equivalent cost-effectiveness as rosuvastatin. 

: In clinical practice, rosuvastatin is more effective and cost-effective in lowering LDL-C and in attainment of ATP III LDL-C goals compared with atorvastatin or simvastatin among high-risk patients.

Coronary heart disease (CHD) continues to be the leading cause of mortality and morbidity in the United States.1 CHD has been identified as 1 of the 5 most costly health conditions to US employers, with a total annual cost of $142 billion.

A wealth of evidence from clinical trials and meta-analyses of trial results clearly demonstrated that statin therapy lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, thereby reducing CHD risk and total mortality.

More recently, clinical data demonstrated that more intensive lipid lowering provides additional clinical benefits.

Evidence-based guidelines issued by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) underline the importance of hyperlipidemia treatment with an aggressive LDL-C goal of <100 mg/dL for high-risk patients.

 Moreover, updated optional recommendations to the ATP III guidelines, published in July 2004, now recommend an optional LDL-C goal of <70 mg/dL in very high-risk patients.

Despite the proven morbidity and mortality benefit of cholesterol reduction and the presence of nationally accepted NCEP guidelines, there is evidence of inadequate hypercholesterolemia management.

 Recent observational studies suggest that many patients who are prescribed statin therapy do not achieve the NCEP goal for LDL-C reduction.

However, there is limited evidence on the effectiveness and the cost-effectiveness of statins in clinical practice, outside of the randomized clinical trial setting, especially among high-risk patients. Additionally, there has been no comparison in high-risk patients of real-world effectiveness between rosuvastatin, atorvastatin, and simvastatin. Because of limited data on realworld effectiveness for different statins among high-risk patients, the objective of the present study was to estimate the clinical effectiveness and cost-effectiveness of rosuvastatin compared with atorvastatin or simvastatin among high-risk patients in the community who were treated by their primary care physicians.

In this retrospective study, patients between the ages of 18 and 79 years treated in 1 of 500 physician offices in the Midwest (Indiana, Michigan, Kentucky, and Ohio) and who had a diagnosis of CHD and/or CHD risk equivalents (according to NCEP ATP III guidelines)16 were eligible for inclusion. CHD risk equivalents were defined as a diagnosis of any 1 of the following conditions: atherosclerosis, ischemic cerebrovascular disease, cerebral atherosclerosis, stroke, peripheral vascular disease, abdominal aortic aneurysm, or diabetes. Additionally for patients to be included in the study, they had to meet the following criteria: (1) at least 1 complete lipid panel result before and after initiating statin therapy; (2) initiated statin therapy between July 1, 2001, and April 31, 2005; (3) no dyslipidemic medications (including bile acid sequestrants, fibric acid, nicotinic acid, ezetimibe, statins) in the 6 months before statin treatment; and (4) no switching to other statins during the study period. Titration of the statin therapy was permitted. Duration of statin therapy was limited to =18 months to minimize differences in the follow-up periods for rosuvastatin compared with atorvastatin and simvastatin. 

The baseline lipid results were defined as the lipid panel obtained closest to (up to 90 days before) the start date of statin therapy. If lipid panel results were not available within 90 days before initiating statin therapy, the patient was excluded from the study. The final lipid results were defined as the lipid panel obtained closest to the end of the study period while the patient was still taking the same statin as at the start of treatment. The final lipid panel had to be obtained at least 4 weeks after initiating statin therapy. The study was limited to patients who were taking rosuvastatin, atorvastatin, or simvastatin, because these are the high-efficacy statins suitable for managing high-risk CHD patients. A total of 775 patients met the eligibility criteria and were included in the study. The following data were abstracted from the patient medical record by the office nurse: diagnosis of CHD or CHD risk equivalent diagnoses, statin therapy type, starting dose, units and frequency, lipid panel results and dates, age, sex, family history of CHD, height, weight, and most recent blood pressure measurement. 

Outcomes of interest were the percentage change in lipid parameters and the proportion of patients attaining ATP III LDL-C <100 mg/dL goal and the NCEP 2004 optional aggressive LDL-C <70 mg/dL goal for very high-risk patients (“very high-risk patientâ€ was defined as having CHD or CHD risk equivalent with a diagnosis of diabetes, acute coronary syndrome, or metabolic syndrome).

Univariate analysis of variance was conducted to detect a difference between rosuvastatin and atorvastatin, and between rosuvastatin and simvastatin in percentage change in the lipid parameters and in the proportion of patients attaining NCEP LDL-C goal levels. Rosuvastatin was used as the reference drug because clinical trials have shown it to be the most efficacious statin monotherapy. Observed change in lipid parameters was derived as the percent change from baseline to final lipid panel results for each patient. The average percent LDL-C change achieved by each statin was computed and differences detected by Student's t test for pairwise comparison. NCEP goal attainment was derived as the proportion of patients with LDL-C levels <100 mg/dL for ATP III goal attainment and LDL-C levels <70 mg/dL for very high-risk patients for the 2004 NCEP guideline update. Multivariate regression analyses were used to adjust for baseline differences among the statin groups, including baseline LDL-C level, age, sex, diagnosis of CHD, and length of statin treatment. Hypertension was not examined in the regression model because it was one of the components in the classification of patients as high CHD risk and thus controlled for in the selection of eligible patients. Standard least-squares regression was used to adjust the percent LDL-C change between the statins for patient characteristics. Logistic regression model coefficients were used to estimate the probability of attaining goal with different treatments, and the sample mean of predicted probabilities was used as an estimate of the expected rate of goal attainment by individual treatment adjusted for patient characteristics. All statistical analyses were conducted using SAS Version 9.1 (SAS Institute Inc, Cary, NC). 

A decision model—based cost-effectiveness analysis was employed to estimate the incremental cost relative to incremental effectiveness between rosuvastatin and atorvastatin, as well as between rosuvastatin and simva-statin. The analysis employed the payer perspective with direct medical costs only and a time horizon of 1 year. Patientlevel effectiveness parameters were taken from the multivariate regression models and included percentage reduction in LDL-C, achievement of ATP III goal, and achievement of the 2004 proposed goal. Resourceuse parameters were based on actual utilization observed in the study cohort and included annualized statin costs and cost of titration. Routine physician visits and laboratory tests were not included because there was no anticipated difference in utilization among the statins.

 Unit costs were based on Medicare reimbursement rates for physician visits associated with titration of the statin doses (measured as the average of the 2006 Medicare Physician Fee Schedule for 99212 and 99213, or $60).

 Unit drug costs were based on the wholesale acquisition cost (WAC) of statins as of March 2006.

 The base-case branded drug price was $2.63 for rosuvastatin (all doses); $2.31 and $3.30 for atorvastatin (10- and 20-mg and higher doses, respectively); and $1.87, $2.51, and $4.37 for simvastatin (5-, 10-, and 20-mg or higher doses, respectively). 

All cost-effectiveness models were estimated using TreeAge Pro Healthcare (TreeAge Software, Inc, Williamson, Mass). Key parameters were subjected to extensive sensitivity analyses with particular attention to the drug cost inputs, given possible generic pricing of simvastatin in late 2006.

Dominance in the incremental cost-effectiveness analyses indicates that a drug treatment is more effective and less costly than an alternate drug treatment. Given that most payers employ tiered patient copayments for generic and brand drugs, different generic and brand patient copayments were assumed to estimate payer costs minus patient payments. Further, manufacturers of brand drugs usually provide a rebate, whereas generic drug manufacturers do not. 

Thus, 4 different scenarios were analyzed that included an assumed rebate of 20% for branded statins (rosuvastatin and atorvastatin) plus variations on the percent discount from WAC for generic simvastatin and differential patient copayments for generic and brand drugs. The 4 scenarios were as follows: (1) 20% brand rebate, 60% discount off WAC for simvastatin, and $10 copay for generics and $25 copay for brand statins; (2) 20% brand rebate, 70% discount off simvastatin WAC price, and $10 generic and $25 brand copay; (3) 20% brand rebate, 60% discount off simvastatin WAC price, and $5 generic and $15 brand copay; and (4) 20% brand rebate, 70% discount off simvastatin WAC price, and $5 generic and $15 brand copay. Additionally, Monte Carlo simulation across all model parameters was conducted for the 2 extreme scenarios (scenarios 2 and 3). The simulations were based on 1000 simulated populations of 10 000 patients each. The Monte Carlo simulation identified situations in which a particular treatment provides acceptable cost-effectiveness based on the payer's willingness-to-pay threshold, as a key model parameter is varied (eg, drug acquisition costs).

Furthermore, a threshold analysis was performed for different copayment levels for willingness-to-pay equal to $0 to determine the price point at which rosuvastatin is preferred over simvastatin using generic simvastatin pricing.

The eligible study population consisted of 775 patients; 63 taking rosuvastatin, 480 taking atorvastatin, and 232 taking simvastatin. Baseline characteristics of the population showed the average age as 61.0 Â± 11.7 years and 52.4% male. Several characteristics differed among the patients taking statins. Rosuvastatin patients were younger and had a higher baseline LDL-C and total cholesterol levels than either atorvastatin or simvastatin patients (

). Because the initial LDL-C level was higher for the rosuvastatin patients, these patients were further from attaining ATP III goals and required a greater LDL-C reduction than atorvastatin or simvastatin patients. The rosuvastatin patients also had a significantly shorter length of statin therapy (125.9 Â± 84.9 days) than atorvastatin or simvastatin patients (260.6 Â± 151.2 days and 264.2 Â± 149.7 days, respectively). The majority of patients were taking 10-mg rosuvastatin (87%), 10-mg atorvastatin (68%), or 20-mg simvastatin (57%), indicating median doses. The mean starting dose of rosuvastatin was 10 mg, whereas the average dose for atorvastatin and simvastatin was 14 mg and 25 mg, respectively.

 Rosuvastatin patients had the greatest observed decrease in LDL-C levels with an average -41.3% Â± 19.5% reduction in LDL-C compared with -28.1% Â± 25.6% for atorvastatin and -25.4% Â± 25.4% for simvastatin patients (

). Multivariate analyses adjusting for baseline differences in age, sex, presence of CHD, baseline LDL-C, and treatment duration also demonstrated that rosuvastatin patients had the greatest percentage decrease (-36.6%) in LDL-C levels that was statistically significantly larger (P <.05) than either atorvastatin or simvastatin (-28.0% or -26.7%, respectively) (Table 2). 

Total cholesterol change among the statins was statistically significantly greater (P <.05) for rosuvastatin users (observed mean change: —30.5% Â± 15.0%, adjusted mean change: —29.0% Â± 1.8%) compared with atorvastatin or simvastatin (Table 2). There was no significant difference in the change in high-density lipoprotein cholesterol and triglycerides among the statins.

NCEP Goal Attainment. NCEP ATP III guidelines recommended a goal of LDL-C <100 mg/dL for high-risk patients and the 2004 update recommended an optional goal of LDL-C <70 mg/dL for very high-risk patients (ie, patients with cardiovascular disease and diabetes, acute coronary syndrome, or metabolic syndrome). After adjusting for differences in baseline characteristics, the odds of attaining NCEP ATP III and the updated ATP III goals were greatest with rosuvastatin users. Atorvastatin users were 50% less likely (odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.27-0.92) and simvastatin users were 57% less likely (OR = 0.43, 95% CI: 0.22-0.82) than rosuvastatin users to attain LDL-C <100 mg/dL (

). Likewise, atorvastatin users had a 56% (OR = 0.44, 95% CI: 0.22-0.87) lower likelihood and simvastatin users had a 69% (OR = 0.31, 95% CI: 0.14-0.64) lower likelihood of attaining the goal than rosuvastatin users when optional updated goals were included in the goal attainment estimation.

After adjusting for differences in baseline characteristics, the estimated percent of patients attaining the ATP III goal was significantly higher (

 <.05) among rosuvastatin patients (69.7%) than among atorvastatin (54.8%) or simvastatin (51.2%) patients (

). Likewise, the adjusted percent attaining ATP III and the optional LDL-C goal for very high-risk patients was significantly greater (

 <.05) among rosuvastatin patients (58.1%) than among atorvastatin (43.4%) or simvastatin (36.9%) patients. 

. In the base-case analysis of drug costs (WAC pricing) and titration costs (physician visits), rosuvastatin had the lowest annualized cost ($962), followed by atorvastatin ($1048) and simvastatin ($1538). Adjusted for differences in patient characteristics, mean annualized costs were $934 for rosuvastatin, $1050 for atorvastatin, and $1545 for simvastatin. Using the adjusted LDL-C reduction and percent attaining goal (both ATP III and optional goal), rosuvastatin was the most cost-effective therapy among the high-risk patients with the lowest adjusted annualized cost per unit of LDL-C reduction ($25), the lowest cost per patient treated to ATP III LDL-C goal of <100 mg/dL ($1340), and the lowest cost per patient treated to the optional LDL-C goal ($1607). For incremental cost-effectiveness, rosuvastatin dominated (less costly and more effective) both atorvastatin and simvastatin for LDL-C reduction and both LDL-C goals (

). Rosuvastatin dominated both atorvastatin and simvastatin on a cost-effectiveness basis (ie, treatment using rosuvastatin entailed lower cost than atorvastatin and simvastatin while also providing greater effectiveness).

Base-case results were most sensitive to the acquisition costs of rosuvastatin, atorvastatin, and simvastatin. Thus, particular focus was placed on the pricing of simvastatin (because generic simvastatin is now available), and on the impact of manufacturer rebates and differential copayment levels on net cost for payers. For LDL-C reduction, when simvastatin price was discounted by 60% and a 20% brand rebate applied, rosuvastatin dominated both atorvastatin and simvastatin for different copay levels ($10 generic/$25 brand for scenario 1 and $5 generic/$15 brand for scenario 3; Table 6). Thus, rosuvastatin was more effective and less costly than atorvastatin and simvastatin when a 20% brand rebate, different patient copays, and a 60% discount on simvastatin price were applied. If simvastatin price were discounted by 70% and the brand rebate and copayments were applied, rosuvastatin had an incremental cost-effectiveness ratio of $9 per 1% LDL-C reduction compared with simvastatin for scenario 2 and $21 for scenario 4 (

). Similarly, the goal attainment sensitivity analyses showed that rosuvastatin dominated atorvastatin and simvastatin when simvastatin pricing was discounted by 60% and a 20% brand rebate and patient copayments were applied (

; scenarios 1 and 3). When simvastatin was discounted by 70% with the brand rebate and copayments applied, simvastatin dominated based on lower price for less effectiveness than rosuvastatin (

; scenarios 2 and 4). In all scenarios evaluated, rosuvastatin dominated atorvastatin. As of October 2006, the generic simvastatin price was $1.58, $2.12, and $3.69, respectively, for 5 mg, 10 mg, and 20 mg and higher. Based on the doses prescribed for the study patients, the average generic simvastatin price was $3.48, approximately a 16% discount from its branded WAC price ($4.12). Given this current generic price, rosuvastatin is more effective and less costly than generic simvastatin.

Sensitivity analyses with Monte Carlo simulation provided the cost-effectiveness acceptability landscape for each outcome of interest and included all 3 statins. For ATP III goal attainment, the likelihood that rosuvastatin was preferred over simvastatin was reached at a willingness-to-pay of $520 for each additional patient attaining LDL-C goal when simvastatin price was 70% less than current WAC and a 20% brand rebate and patient copay of $10 generic and $25 brand were applied. When simvastatin price was reduced to 60% of WAC and a 20% brand rebate and $5 generic and $15 brand copay were applied, the likelihood that rosuvastatin was preferred over simvastatin was achieved at willingness-to-pay equal to $0.

The threshold analysis demonstrated that rosuvastatin dominated simvastatin at any generic price of simvastatin above the threshold of 30% to 40% of current WAC (

). When the differential in patient copayment was the smallest ($5 generic/$15 brand), the threshold for generic simvastatin price was highest, approximately 40% of WAC. With a copayment differential of $15 between generic and brand, the threshold was approximately 35% of WAC. The threshold dropped to 31% to 32% when the copayment differential was $20.

Rosuvastatin was more effective in lowering LDL-C (—36.7% change) and total cholesterol (—29.0% change) in high-risk patients. Rosuvastatin was more effective in getting patients to attain NCEP ATP III and the updated optional NCEP goals compared with atorvastatin and simvastatin. In addition, rosuvastatin provided greater treatment effectiveness at lower treatment costs than atorvastatin and simvastatin for high-risk patients in clinical practice in both LDL-C reduction and NCEP goal attainment. Thus, in base-case models, rosuvastatin dominated both atorvastatin and simvastatin as treatment strategies, because atorvastatin and simvastatin were less effective and more costly than rosuvastatin among patients treated in the community. The implications of these findings are important for managed care decision makers. Under the base-case analysis, atorvastatin and simvastatin were always dominated. Thus, payers may achieve substantial cost savings and greater effectiveness among high-risk patients by using rosuvastatin rather than atorvastatin or simvastatin, depending on the actual acquisition prices.

The sensitivity analyses tested the pricing range for simvastatin and atorvastatin versus rosuvastatin in addition to applying a rebate for branded statins and differential patient copayments. Managed care organizations (MCOs) are provided with rebates on branded drugs. Additionally, in health plans using pharmacy benefit designs with tiered copayments, the differential cost between branded rosuvastatin and generic simvastatin for the health plans would be further reduced by higher patient copays for a branded versus generic drug. As simvastatin transitions to a generic product, rebates will continue to be provided for rosuvastatin and atorvastatin and patient copayments will differ, closing the gap between the cost differential. Our findings confirm that rosuvastatin will continue to dominate simvastatin with a 60% discount off WAC, a 20% brand rebate, and a differential of $10 in patient copays. The threshold analysis also affirmed that rosuvastatin dominated simvastatin at all generic simvastatin pricing above 31% to 40% of current WAC for LDL-C reduction and goal attainment. Hence, the pricing of simvastatin would have to be discounted by at least 60% to achieve superior cost-effectiveness based on lower price with less effectiveness than rosuvastatin. Even if this simvastatin discount was achieved, individual patient needs (in terms of the extent of LDL-C reduction desired) would need to be considered for selecting generic simvastatin or the more effective rosuvastatin.

It is important for MCOs to have as many patients as possible achieve NCEP goals, because several quality-of-care initiatives are based on these goals. The National Committee for Quality Assurance Health Plan Employer Data and Information Set establishes benchmarks for quality of care provided by MCOs for patients after an acute cardiovascular event based on the proportion of patients achieving NCEP goals.

 Additionally, several pay-for-performance programs

 are currently in place to reward physicians who intensively treat their patients and get them to the NCEP target goals.

This study is unique because it is based on actual clinical practice. The LDL-C reduction and NCEP goal attainment were the outcomes observed among patients from different physician offices on their usual care regimen rather than patients selected and randomized in a clinical trial. Other investigations have quantified the efficacy

 of statin therapy from clinical trial data that included a select group of patients. The results from our study are similar to those investigations using clinical trial data. Rosuvastatin was shown to be the most efficacious statin,

 and we found rosuvastatin to be the most effective of the 3 high-efficacy statins in clinical practice. Similar to our findings, Benner and colleagues

 found rosuvastatin to be the most cost-effective statin and dominated atorvastatin, pravastatin, and simvastatin under the base-case and several alternative scenarios using data derived from clinical trials.

Moreover, this study uniquely focused on those high-risk patients who have been diagnosed with CHD and required intensive lipid-lowering therapy according to the NCEP ATP III guidelines. Other investigators have examined either the overall effectiveness of statin therapy or effectiveness in different patient populations at various risk levels depending on the clinical trial population or the composition of their health plan.

 Similar to our findings, several recent investigations have shown that rosuvastatin was more effective in LDL-C reduction than other statins.

Bullano and colleagues showed that a greater percent of patients reached NCEP ATP III LDL-C goal with rosuvastatin compared with all other statins for high- and moderate-risk patients.

 Our study confirmed this greater effectiveness of rosuvastatin for LDL-C reduction and goal attainment compared with atorvastatin and simvastatin among the high-risk patients who require intensive lipid-lowering therapy. Recent evidence has confirmed the clinical benefits of aggressive lipid lowering, particularly in patients with an elevated risk for CHD.

The study findings should be interpreted in light of several limitations. The patients are from physician practices in the Midwest, and the treatment patterns observed in this group of patients may not be representative of clinical practice in other areas of the United States. However, our findings are similar to other reported studies of patients in Western and Southeastern health plans.

Costs were estimated using published WAC for drugs and Medicare reimbursement rates for physician visits for drug titration. These costs may not reflect the actual costs negotiated by MCOs, but wide variations in these parameters were tested to find relevant thresholds that changed rosuvastatin dominance. Costs associated with laboratory procedures, adverse drug events, and routine physician visits were excluded, but these costs were not expected to differ across treatment groups and therefore would not have affected the incremental cost-effectiveness analysis. 

The duration of statin therapy was limited to ≤18 months because rosuvastatin was new to the market and patients did not have the opportunity to receive rosuvastatin for as long as atorvastatin and simvastatin. However, therapy duration was still shorter for rosuvastatin patients compared with those taking the other statins (126 vs 261-264 days, respectively). Controlling for therapy duration did not impact the results for LDL-C reduction or goal attainment. The analysis had a 1-year time horizon and thus examined short-term end points (LDL-C reduction and ATP III goal attainment) instead of long-term outcomes, such as cost per life-year gained or cost per avoided CHD event. A longer follow-up period or analytic model would be required to estimate the long-term outcomes.

Fewer patients were taking rosuvastatin than atorvastatin or simvastatin. This was expected, because the study period included market introduction of rosuvastatin and thus less use of rosuvastatin compared with atorvastatin or simvastatin in clinical practice. Future studies with more robust sample sizes could be used to confirm the present study results. Also, the study did not allow for switching and therefore may have selected patients without any tolerability issues with the individual statins. Our analyses applied the optional LDL-C goal of <70 mg/dL for all very high-risk patients even though the goal was not recommended until 2004. Therefore, considering this limitation, our findings with regard to attaining the optional LDL-C goals should be interpreted

In conclusion, the findings indicated that managing hyperlipidemia patients with rosuvastatin is more effective and less costly than with atorvastatin or generic simvastatin (at current prices). Moreover, a substantial discount from the current branded price would be needed for generic simvastatin to be equally as cost-effective as rosuvastatin for payers. These findings reflect treatment effectiveness as observed in clinical practice for patients treated with statin therapy rather than the efficacy demonstrated for doses used in clinical trials.

Department of Health Policy and Management

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 Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trialâ€”Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. 

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 Intensive versus moderate lipid lowering with statins after acute coronary syndromes. 

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Effectiveness and Cost-effectiveness of Rosuvastatin, Atorvastatin, and Simvastatin Among High-Risk Patients in Usual Clinical Practice

Recently, statin safety and potential drug interactions have received close attention in the consumer and medical press. In particular, rosuvastatin, the most recent statin introduced into the US market, has been the object of much speculation. Many of these reports have lost sight of the proven efficacy of statins in coronary disease prevention at a time when coronary heart disease is the number one killer of adults, and have failed to frame the potential drug toxicity in the context of this benefit. Summarized here are the conclusions of the National Lipid Association's Statin Safety Assessment Task Force, which reviewed extensive new drug application (NDA) and postmarketing data for all the currently marketed statins regarding their effect on the liver, muscle, renal, and neurologic systems. 

The task force found that, overall, hepatic, renal, or neurologic function does not appear to be compromised by statin use. They do not recommend routine monitoring of these systems but do recommend ongoing surveillance of symptomatic patients. With respect to muscle toxicity, the task force's Muscle Expert Panel concluded that the incidence of myopathy and rhabdomyolysis is low and appears to be dose-related, rather than associated with the degree of low-density lipoprotein cholesterol lowering and also appears to be related to the individual statin used. For example, from the rosuvastatin NDA database and additional postmarketing data, the overall incidence of myopathy was found to be lower than that observed with other statins. 

Administrative claims data of hospitalization rates for adverse events in statin patients confirm the task force conclusion that, overall, statins are safe and well tolerated when used as monotherapy. 

Concern over the safety of statins has flourished since the removal of cerivastatin from the market in 2001. Cerivastatin was associated with more than 100 deaths from rhabdomyolysis, with most cases of muscle toxicity occurring in patients cotreated with the fibric acid derivative gemfibrozil.

Since then, statin safety and potential drug interactions have received close scrutiny in the consumer and medical press. The most recent statin introduced into the US market–rosuvastatin–has been the object of much speculation regarding its potential role in kidney failure as a result of an association with proteinuria. Other concerns raised have been potential effects of statins on the liver and on cognition. 

The news media emphasis on potential severe side effects has influenced many patients to refuse to initiate therapy or withdraw from long-term treatment. The attention has caused many physicians to lose confidence in the benefit-safety profile of these agents as well. Frequent references to potential adverse events have pervaded the doctor-patient relationship. Unfortunately, many of these reports have lost sight of the proven efficacy of statins in coronary disease prevention at a time when coronary heart disease is the number one killer of adults, and have failed to frame the potential drug toxicity in the context of this benefit.

To address the concerns over statin safety, the National Lipid Association's Statin Safety Assessment Task Force issued its conclusions and recommendations recently in a supplement to the 

The task force commissioned expert reviews, carried out analyses of the major sources of adverse reaction information (the US Food and Drug Administration [FDA] Adverse Event Reporting System [AERS], administrative claims databases from managed care organizations, new drug applications [NDAs], cohort studies, and clinical trials), and appointed 4 independent teams of medical subspecialists to assess the effect of statins on the liver,

systems. Following is a summary of the report. 

All statins are associated with asymptomatic elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels >3 times the upper limit of normal (ULN) at a rate of <1% at starting and intermediate dosages.

This rate increases up to 2% to 3% in those receiving 80 mg/day of any statin.

From an analysis of 180 000 patients who participated in 21 major statin trials lasting an average of 3 years, the incidence of a liver function test (LFT) elevation >3 times the ULN on 1 occasion was found to be 300 cases per 100 000 person-years, whereas that for 2 consecutive elevations was 110 cases per 100 000 person-years (the incidence of similar elevations among placebo patients was 200 and 40 cases per 100 000 person-years, respectively).

These elevations are most often transient and resolve spontaneously even with continued statin use and without dose reduction. Although there is a dose relationship to LFT elevations, data from clinical trials indicate that increases are unrelated to the degree of low-density lipoprotein cholesterol (LDL-C) lowering with a statin.

In a "real-life" evaluation of 23 000 patients treated with statins in a health maintenance organization,

17 of 62 cases of markedly elevated ALT levels were thought to be statin-related, 13 of which were associated with potential drug interactions. Of the other 4 cases, 3 patients had heart disease, diabetes, or both. The remaining case was a 71-year-old woman on the highest marketed dose (80 mg) of atorvastatin. These data confirm that marked sustained elevations in liver enzymes are rare and may be affected by potential drug interactions and comorbidities or use of the highest dose of a statin. 

Most important, the expert panel of hepatologists who examined this adverse effect was unable to find a link between changes in LFTs and outright episodes of liver failure. They concluded that isolated elevations of aminotransferase are not linked with acute or chronic liver injury.

Few cases of liver failure have been reported in statin users. According to the FDA AERS database through 1999, 1 case of liver failure was reported per 1 million statin prescriptions; this is the same prevalence as the 1 case of liver failure per million reported in nonstatin-taking populations.

Furthermore, only 1 patient of 51 741 who received a liver transplant between 1990 and 2002 was taking a currently marketed statin.

According to the Liver Expert Panel, "?liver failure may occur very rarely with statin therapy?the risk of liver failure is present with any statin, but the risk is quite remote."

The Statin Safety Assessment Task Force concludes from the data mentioned that routine monitoring of LFTs in asymptomatic statin users does not appear warranted (

The task force recommended obtaining liver transaminase levels in the general evaluation of patients who are being considered for a statin, and continuing periodic measurement of transaminase levels only for medical-legal reasons, taking into consideration that the FDA-approved package labeling calls for monitoring of LFTs.

A more sensible approach to detecting hepatotoxicity in statin recipients, in the view of the task force, is to carry out ongoing surveillance of significant symptoms of hepatic dysfunction, including jaundice, malaise, fatigue, and lethargy, and when symptoms are found, to obtain a fractionated bilirubin level, rather than periodic monitoring of aminotransferase levels.

The Liver Expert Panel further stated that neither chronic liver disease nor compensated cirrhosis should be considered contraindications to statin therapy, but believes that decompensated cirrhosis or acute liver failure should remain a contraindication.

Proteinuria and hematuria have rarely been described with all of the statins.

The proteinuria is probably not a toxic effect but a physiologic effect that is central to the mechanism of lowering cholesterol. 

Despite the mild proteinuria that has been reported most prominently with rosuvastatin but also with all statins, short-and long-term renal function is not compromised with the use of statins. In fact, the evidence indicates that statin therapy may be associated with an improvement in renal function. In a meta-analysis of 13 clinical trials in which the effect of lipid-modifying drugs on renal function was examined, these therapies preserved glomerular filtration rate and reduced the level of proteinuria in patients with existing renal disease.

Cases of renal failure occur with the same frequency in patients taking and not taking statins. In placebo-controlled, randomized trials with pravastatin, more cases of renal failure and other renal diseases occurred in patients randomized to placebo.

Therefore, statin therapy does not appear to cause acute renal failure or insufficiency in the absence of rhabdomyolysis.

The Statin Safety Assessment Task Force concludes that during the management of patients with statin therapy, it is not necessary to routinely carry out serum creatinine and proteinuria monitoring for the purpose of identifying an adverse effect, although an assessment of renal function is advisable before initiating statin therapy (

Nevertheless, rosuvastatin has come under increased public scrutiny for its potential relationship to kidney failure and proteinuria, probably as a result of its development after cerivastatin was withdrawn. The task force found that these concerns are unwarranted. In a retrospective comparison of rosuvastatin with atorvastatin, simvastatin, pravastatin, and placebo, using the rosuvastatin 12 500-patient NDA database, there was no significant difference in the incidence of combined proteinuria and hematuria (0%-0.3%) between the statins or between doses of the statins, and urine dipstick protein results comparing baseline with values at the final visit were not different between any of the statins and placebo.

Further, no decline in renal function was observed in patients with or without diabetes who were treated with rosuvastatin for up to 3.8 years. 

the FDA stated that there is no evidence that renal injury/failure could be linked causally to rosuvastatin or any other statin. The conclusion with respect to rosuvastatin was reached on a premarketing experience that included more than 12 000 patients and "a substantial number of study participants with mild-to-moderate renal impairment."

Case reports and a few small cohort studies suggest that statins may have neurologic adverse effects on the central nervous system (CNS).

Findings from larger clinical trials do not support a cause for concern, and in fact, some even point to a possible favorable effect of statins on CNS disorders such as Alzheimer's disease and dementia.

In 2 large clinical trials of statins–the Heart Protection Study (HPS)

and the Prospective Study of the Elderly at Risk (PROSPER)

–in which more than 26 000 patients were randomized to either placebo or simvastatin (HPS) or pravastatin (PROSPER), there was no decline in cognitive function among the patients allocated to a statin compared with those assigned placebo. 

In studies of statin use and incident dementia and/or Alzheimer's disease, statins have had either a neutral or beneficial effect on these end points.

Other studies suggest potential improvement in various cognitive scales in patients with Alzheimer's disease who were taking statins.

Statins have had a pronounced favorable effect on the risk of thrombotic stroke in clinical trials. In a meta-analysis of 58 clinical trials, the relative reduction in nonhemorrhagic stroke risk with statin use was as great as 17% compared with placebo.

Statins' role in peripheral nervous system adverse events has also been examined. Literature reviews indicate that any such risk of peripheral neuropathy with statin use and idiopathic peripheral neuropathy is very small.

In an examination of an electronic pharmacy claims database that included 17 219 persons who had received at least 1 prescription for lipid-lowering drugs, no significant association between idiopathic peripheral neuropathy and statin use could be identified.

Routine neurologic monitoring of patients administered statin therapy for changes indicative of peripheral neuropathy or impaired cognition is not recommended.

 However, if the patient experiences either of these problems while receiving statin therapy, it is appropriate to first look for other etiologies, and if none are found, to withdraw the statin for 1 to 6 months. If improvement is not seen, statin therapy should be restarted based on a risk-benefit analysis (

The effect of statins on creatine kinase (CK) levels and muscle pain, weakness, or cramps and their association with rhabdomyolysis have received the most attention of the potential statin toxicities. In clinical trials, rates of muscle complaints are similar in statin and placebo recipients.

The rates observed in clinical trials should be viewed with caution, however, given that clinical trials include patients who have a low risk of statin-induced muscle injury. 

concluded that myopathy and rhabdomyolysis are likely a class effect with the statins. The potential to cause adverse muscle experiences, however, probably differs with the individual statins and depends on the blood level achieved. In the case of cerivastatin monotherapy, more deaths due to rhabdomyolysis occurred at the highest marketed dose, 0.8 mg, than with the lower doses.

 Gemfibrozil coadministration, which increases cerivastatin blood levels, was a factor in many cerivastatin-related deaths. 

The relative muscle toxicity between therapies is unknown because comparisons between statins (or other lipid-lowering therapies) are absent, wrote the Muscle Expert Panel, which also found an evaluation of the data with respect to muscle toxicity to be difficult because no standard definitions of myopathy or rhabdomyolysis exist.

In a review of the statin NDAs, additional studies were required for rosuvastatin after an increase in awareness of safety issues generated by the experience with cerivastatin and rhabdomyolysis. With the additional studies, 12 569 patients were included in the revised NDA for rosuvastatin in 2003.

About 4000 patients in this database were treated with 40 mg of rosuvastatin, the highest dose that was eventually approved. This number was greater than the number of patients treated with any dose of any other statin. Also, recipients of the 40-mg dose were treated for at least 1 year, and 1100 patients received it for 2 years, representing a high level of exposure compared with the patients in the NDA databases for the other statins. The rosuvastatin NDA database included many high-risk patients with significant comorbidities to better reflect the actual users of the drug. The review for rosuvastatin was therefore more critical than it was for the other statins in light of the cerivastatin experience. 

James M. McKenney, PharmD

Articles

Understanding Practice Patterns and Low-density Lipoprotein Cholesterol Goal Attainment Implications of Switching Patients From Simvastatin in a Health Plan Setting

Effectiveness and Cost-effectiveness of Rosuvastatin, Atorvastatin, and Simvastatin Among High-Risk Patients in Usual Clinical Practice

An Assessment of Statin Safety

Statin Pharmacology May Have Important Clinical Implications