Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II

Article Outline

• Abstract
• Methods
  • Trial design
  • Laboratory methods
  • Statistical analysis
  • Safety analysis
• Results
  • Demographics and baseline values
  • Changes in LDL-C levels
  • LDL-C target achievement
  • Changes in other lipids and lipoproteins
  • LDL-C, non–HDL-C, and apo B target achievement in hypertriglyceridemic patients
  • Safety
• Discussion
• Acknowledgment
• References
• Copyright

Abstract 

Background

National Cholestesrol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of <100 mg/dL. This target can be difficult to attain with diet and current therapy.

Methods

In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks.

Results

At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of <70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides ≥200 mg/dL) met LDL-C, non–high-density lipoprotein cholesterol (non–HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non–HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity.

Conclusion

Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.

Low-density lipoprotein cholesterol (LDL-C) reduction remains the primary target of lipid-lowering therapy to reduce the risk of coronary heart disease (CHD).¹, ² National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines recommend reduction of LDL-C to <100 mg/dL in high-risk patients.¹ An optional LDL-C target of <70 mg/dL has been proposed for patients with very high risk (CHD with multiple major or uncontrolled risk factors).² High-risk patients frequently have elevated triglycerides (TG), with increased concentration of small, dense LDL particles, and therapeutic targets for non–high-density lipoprotein cholesterol (non–HDL-C) and apolipoprotein (apo) B-100 have been recommended for these individuals.¹, ³ Because of increasingly aggressive targets, many patients, even among those on statin therapy, are not at target.⁴ An important option to achieve targets is to change from a less effective to a more effective statin. In this regard, rosuvastatin has been shown to reduce LDL-C more than many other statins.⁵

We examined the achievement of LDL-C targets in high-risk patients as well as secondary non–HDL-C and apo B targets in patients with elevated TG, when treated with the most widely prescribed doses of atorvastatin and simvastatin compared with switching to rosuvastatin at its most widely used doses. We also report LDL-C reductions and changes in apolipoproteins with different regimens of statin therapy.

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Methods 

Trial design 

This randomized, open-label, phase IIIb trial (4522IL/0068) was conducted at 152 centers in the United States, Canada, Argentina, Brazil, and Mexico in accordance with the Declaration of Helsinki and in compliance with the ethical principles of good clinical practice. Appropriate ethics committees or institutional review boards approved the trial, and all patients provided written, informed consent before any trial procedure. Eligible patients were men and women aged ≥18 years who had (1) high risk of CHD events—documented history of CHD or other established atherosclerotic disease, diabetes, or ATP III–defined 10-year CHD risk ¹ >20%, regardless of prior statin treatment; (2) fasting LDL-C level ≥130 to <250 mg/dL (≥3.36 to <6.46 mmol/L), based on 2 measurements within 15% or, if the difference exceeded 15%, a third sample was taken and the last 2 values used for LDL-C determination; and (3) fasting TG <400 mg/dL (<4.52 mmol/L). Exclusion criteria included pregnancy or lactation; history of homozygous familial hypercholesterolemia or known hyperlipoproteinemia types I, III, IV, or V; unstable arterial disease within 3 months of trial entry; uncontrolled hypertension; fasting serum glucose of >180 mg/dL (>10.0 mmol/L) at any time during dietary lead-in; active liver disease or hepatic dysfunction (transaminases or bilirubin ≥1.5 times upper limit of normal [ULN]); serum creatinine of >2.0 mg/dL (>177 μmol/L); or unexplained serum creatine kinase (CK) levels >3 times ULN.

After a 6-week dietary lead-in (discontinuation of all cholesterol-lowering treatments and instruction in ATP III Therapeutic Lifestyle Change Diet), eligible patients were randomized to 1 of 5 treatment groups (Figure 1): rosuvastatin 20 mg (arm 1), atorvastatin 10 mg (arm 2), atorvastatin 20 mg (arm 3), simvastatin 20 mg (arm 4), or simvastatin 40 mg (arm 5) for 8 weeks (period 1). During the 8 weeks of period 2, patients in arm 1 continued receiving rosuvastatin 20 mg, whereas patients in the other treatment arms either remained on initial treatment or switched from atorvastatin 10 mg to rosuvastatin 10 mg (arm 2), atorvastatin 20 mg to rosuvastatin 20 mg (arm 3), simvastatin 20 mg to rosuvastatin 10 mg (arm 4), and simvastatin 40 mg to rosuvastatin 20 mg (arm 5).

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• Figure 1. 

  Trial design. Treatment arms and number of patients randomized.

Efficacy analyses were performed for the intention-to-treat population (all patients who received randomized treatment and had a baseline and ≥1 postbaseline lipid measurement for the appropriate treatment phase), with the last observation carried forward. Baseline lipids were the average of measurements at weeks −2, −1, and 0; lipids were subsequently measured at the end of each 8-week treatment period. Primary efficacy measure was the proportion of patients achieving LDL-C <100 mg/dL¹ at week 16. Secondary efficacy measures included proportions of patients meeting the LDL-C target at week 8 and changes in lipid and lipoprotein measures at weeks 8 and 16. Supplemental analyses included proportions of hypertriglyceridemic (TG ≥200 mg/dL) patients who met both lipid targets (LDL-C <100 mg/dL; non–HDL-C <130 mg/dL) and the suggested apo B target of <90 mg/dL³ and proportions of very high risk patients reaching the optional LDL-C target of <70 mg/dL.² Very high risk patients were those with established cardiovascular disease plus one or more of the following: multiple major risk factors, severe and poorly controlled risk factors, and multiple risk factors of the metabolic syndrome.

Laboratory methods 

All laboratory samples were analyzed at a central laboratory (Medical Research Laboratories, Highland Heights, KY), as described previously.⁵, ⁶

Statistical analysis 

For the primary and secondary efficacy measures assessing cholesterol target achievement, comparisons were made between treatment arms for period 1 and within treatment arms for period 2 using logistic regression. Treatment and region were fitted as factors, and baseline LDL-C was included as a covariate; period 1 response was fitted as a factor in period 2 analyses. Between- and within-arm comparisons of changes in LDL-C and other lipid values from baseline were performed using analysis of variance models with factors fitted for treatment and region. Results are shown as least-squares mean percentage changes from baseline and P values from analysis of variance. The Bonferroni correction⁷ was applied for all period 1 comparisons for target achievement and lipid changes with a 2-sided significance level requirement of .0125. All period 2 pairwise comparisons had a 2-sided significance level requirement of .05.

Safety analysis 

Safety assessments included adverse event reports, clinical laboratory data, vital signs, and physical examination. All randomized patients receiving at least 1 dose of study medication were included in safety analyses. Safety data were summarized by descriptive statistics.

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Results 

Demographics and baseline values 

A total of 1993 patients were randomized to 1 of 5 treatment groups during period 1 (Figure 1); of these, 1983 received at least 1 dose of study treatment. Period 1 treatment groups were well matched with regard to demographics and baseline characteristics (Table I) and baseline lipid levels (Table II). A total of 208 patients (10.4%) discontinued treatment during the study (118 during period 1 and 90 during period 2); adverse events were the most common reason for withdrawal, accounting for 52 patients in period 1 and 32 in period 2.

Table I. Demographic and baseline characteristics by period 1 treatment

Characteristic, n (%) unless noted	Randomized population (n = 1993)
Male	1112 (55.8%)
Age, y, mean (SD)	61.9 (10.4)
≥65 y	826 (41.4%)
Weight, kg, mean (SD)	87.4 (19.8)
Body mass index, kg/m2, mean (SD)	30.64 (6.1)
>30 kg/m2	939 (47.1%)
Race
White	1587 (79.6%)
Hispanic	201 (10.1%)
Black	156 (7.8%)
Asian	32 (1.6%)
Other⁎	17 (0.9%)
CHD or CHD risk equivalents	1235 (62.0%)
Diabetes	900 (45.2%)
TG ≥200 mg/dL	725 (36.4%)

Table II. Least-squares mean % change (SE) in lipid and apolipoprotein measures from baseline at 8 weeks

	RSV 20 mg (n = 383)	ATV 10 mg (n = 389)	ATV 20 mg (n = 383)	SIM 20 mg (n = 387)	SIM 40 mg (n = 391)
LDL-C
Baseline, mg/dL (SD)	167.1 (27.4)	169.0 (27.5)	168.1 (26.2)	169.4 (25.8)	168.8 (27.8)
% change	−52.1 (0.7)	−37.1 (0.7)⁎	−43.3 (0.7)⁎	−34.2 (0.7)⁎	−41.2 (0.7)⁎
Total cholesterol
Baseline, mg/dL (SD)	250.7 (32.4)	252.9 (32.5)	250.9 (32.3)	252.9 (31.3)	252.4 (31.6)
% change	−37.1 (0.5)	−26.5 (0.5)⁎	−31.6 (0.5)⁎	−24.1 (0.5)⁎	−28.9 (0.5)⁎
Triglycerides
Baseline, mg/dL (SD)	182.0 (75.9)	184.0 (65.8)	181.3 (68.3)	183.1 (66.0)	184.9 (67.5)
% change	−22.8 (1.3)	−17.7 (1.2)†	−21.4 (1.3)	−13.3 (1.2)⁎	−15.6 (1.2)⁎
HDL-C
Baseline, mg/dL (SD)	47.3 (11.9)	47.2 (11.0)	46.7 (10.2)	47.0 (10.1)	46.9 (11.4)
% change	+6.9 (0.6)	+5.3 (0.6)	+3.7 (0.6)⁎	+5.4 (0.6)	+5.9 (0.6)
Non–HDL-C
Baseline, mg/dL (SD)	203.4 (33.0)	205.8 (32.5)	204.2 (32.5)	205.9 (30.4)	205.5 (32.5)
% change	−47.2 (0.7)	−33.7 (0.6)⁎	−39.6 (0.7)⁎	−30.8 (0.6)⁎	−36.7 (0.6)⁎
LDL-C/HDL-C
Baseline ratio (SD)	3.75 (1.09)	3.76 (0.99)	3.77 (1.00)	3.77 (0.94)	3.81 (1.10)
% change	−54.7 (0.7)	−39.8 (0.7)⁎	−44.7 (0.7)⁎	−37.3 (0.7)⁎	−44.2 (0.7)⁎
Total cholesterol/HDL-C
Baseline ratio (SD)	5.60 (1.43)	5.61 (1.31)	5.62 (1.33)	5.61 (1.22)	5.68 (1.42)
% change	−40.6 (0.6)	−29.7 (0.6)⁎	−33.5 (0.6)⁎	−27.5 (0.6)⁎	−32.3 (0.6)⁎
Non–HDL-C/HDL-C
Baseline ratio (SD)	4.60 (1.43)	4.61 (1.31)	4.62 (1.33)	4.61 (1.22)	4.68 (1.42)
% change	−50.0 (0.7)	−36.4 (0.7)⁎	−41.1 (0.7)⁎	−33.7 (0.7)⁎	−39.7 (0.7)⁎
Apo B
Baseline, mg/dL (SD)	159.0 (27.7)	160.6 (27.4)	160.3 (25.8)	162.6 (26.0)	161.8 (26.3)
% change	−40.9 (0.6)	−28.9 (0.6)⁎	−34.9 (0.6)⁎	−26.8 (0.6)⁎	−32.2 (0.6)⁎
Apo A-I
Baseline, mg/dL (SD)	151.4 (28.1)	151.9 (26.7)	150.4 (25.8)	152.8 (25.5)	150.8 (26.9)
% change	+3.8 (0.6)	+3.2 (0.6)	+1.3 (0.6)†	+2.6 (0.6)	+4.4 (0.6)
Apo B/apo A-I
Baseline ratio (SD)	1.09 (0.29)	1.09 (0.26)	1.10 (0.26)	1.09 (0.24)	1.11 (0.28)
% change	−42.5 (0.7)	−30.6 (0.7)⁎	−35.0 (0.7)⁎	−28.0 (0.7)⁎	−34.4 (0.7)⁎
Achieved LDL-C <100 mg/dL at week 8, n (%)	315 (82%)	167 (43%)⁎	237 (62%)⁎	126 (33%)⁎	210 (55%)⁎

ATV, atorvastatin; RSV, rosuvastatin; SIM, simvastatin.

Changes in LDL-C levels 

Table II summarizes changes from baseline in lipid and apolipoprotein measures at 8 weeks. After 8 weeks, rosuvastatin 20 mg reduced LDL-C more than atorvastatin 10 or 20 mg or simvastatin 20 or 40 mg (all P < .0001). Table III summarizes those changes at 16 weeks. At 16 weeks, switching to rosuvastatin produced significant reductions in LDL-C compared with remaining on atorvastatin or simvastatin (all within-arm comparisons P < .001). Figure 2 shows LDL-C values at 8 and 16 weeks for both patients who remained on initial treatment and those who switched to rosuvastatin. Switching to rosuvastatin produced a significantly greater incremental percent reduction in LDL-C compared with staying on initial therapy (all within-arm comparisons P < .001).

Table III. Least-squares mean % change^⁎ (SE) in lipid and apolipoprotein measures from baseline at 16 weeks after switching to rosuvastatin or remaining on comparator statin for 8 weeks

	Treatment arm
Period 1	RSV 20 mg	ATV 10 mg		ATV 20 mg		SIM 20 mg		SIM 40 mg
Period 2	RSV 20 mg (n = 362)	ATV 10 mg (n = 180)	RSV 10 mg (n = 189)	ATV 20 mg (n = 182)	RSV 20 mg (n = 184)	SIM 20 mg (n = 185)	RSV 10 mg (n = 179)	SIM 40 mg (n = 183)	RSV 20 mg (n = 183)
LDL-C
% change	−51.6 (0.8)	−36.2 (1.1)	−46.6 (1.1)†	−43.4 (1.2)	−50.8 (1.2)†	−32.1 (1.1)	−45.5 (1.1)†	−39.6 (1.1)	−53.7 (1.1)†
Total cholesterol
% change	−36.7 (0.6)	−25.9 (0.83)	−32.6 (0.8)†	−31.6 (0.9)	−36.5 (0.9)†	−22.7 (0.9)	−32.0 (0.9)†	−27.6 (0.8)	−38.1 (0.9)†
Triglycerides
% change	−21.6 (1.2)	−16.2 (2.6)	−17.7 (2.7)	−22.0 (2.1)	−20.7 (2.0)	−10.9 (1.9)	−18.6 (1.9)‡	−15.8 (1.9)	−23.3 (2.0)§
HDL-C
% change	+7.2 (0.7)	+6.1 (1.0)	+7.5 (1.0)	+4.0 (1.0)	+5.3 (1.0)	+4.3 (1.0)	+6.3 (1.0)	+6.9 (1.0)	+7.6 (1.0)
Non–HDL-C
% change	−46.7 (0.7)	−33.1 (1.0)	−41.8 (1.0)†	−39.8 (1.1)	−45.7 (1.1)†	−28.7 (1.1)	−40.7 (1.1)†	−35.3 (1.0)	−48.6 (1.0)†
LDL-C/HDL-C
% change	−54.3 (0.8)	−38.9 (1.2)	−50.0 (1.2)†	−44.8 (1.3)	−52.6 (1.3)†	−33.8 (1.3)	−48.3 (1.3)†	−43.2 (1.1)	−56.5 (1.1)†
Total cholesterol/HDL-C
% change	−40.3 (0.7)	−29.2 (1.0)	−37.0 (1.1)†	−33.4 (1.1)	−38.8 (1.1)†	−24.6 (1.1)	−35.5 (1.1)†	−31.7 (0.9)	−41.9 (0.9)†
Non–HDL-C/HDL-C
% change	−49.5 (0.8)	−35.7 (1.3)	−45.4 (1.3)†	−41.2 (1.3)	−47.5 (1.3)†	−30.1 (1.3)	−43.6 (1.3)†	−38.9 (1.0)	−51.6 (1.1)†
Apo B
% change	−40.2 (0.7)	−26.9 (1.1)	−36.3 (1.1)†	−35.4 (1.1)	−40.4 (1.1)†	−25.0 (1.0)	−36.2 (1.0)†	−31.4 (1.0)	−42.6 (1.0)†
Apo A-I
% change	+4.0 (0.6)	+2.5 (0.9)	+4.1 (0.9)	+1.2 (1.0)	+3.6 (1.0)	+2.1 (1.0)	+3.5 (1.0)	+5.1 (1.0)	+5.3 (1.0)
Apo B/apo A-I
% change	−41.9 (0.8)	−27.8 (1.1)	−38.5 (1.1)†	−35.4 (1.2)	−41.7 (1.2)†	−25.8 (1.1)	−37.7 (1.1)†	−34.1 (1.0)	−44.9 (1.0)†

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• Figure 2. 

  Differences in incremental least-squares mean percentage changes in LDL-C between week 8 and week 16 after switching to rosuvastatin (RSV) or remaining on atorvastatin (ATV) or simvastatin (SIM) for 8 weeks. (A) Switching to RSV 10 mg vs remaining on ATV 10 mg; (B) switching to RSV 20 mg vs remaining on ATV 20 mg; (C) switching to RSV 10 mg vs remaining on SIM 20 mg; (D) switching to RSV 20 mg vs remaining on SIM 40 mg. *Difference between incremental least-squares mean % changes in LDL-C from week 8 to week 16.

LDL-C target achievement 

The proportion of patients who achieved the ATP III LDL-C target of <100 mg/dL at 8 weeks on initial therapy is shown in Table II. Figure 3 shows that switching to rosuvastatin significantly increased the proportion of patients reaching this target at 16 weeks compared with remaining on initial therapy (P < .001 for all comparisons). Differences in target achievement rates between rosuvastatin and atorvastatin or simvastatin ranged from 15.1% to 41.7%.

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• Figure 3. 

  Proportions of patients achieving ATP III LDL-C goal <100 mg/dL at 16 weeks after switching to rosuvastatin (RSV) or remaining on atorvastatin (ATV) or simvastatin (SIM) after 8 weeks. *P < .001 for within-arm comparison of rosuvastatin vs atorvastatin or simvastatin.

A total of 1011 of the randomized patients who were categorized as very high risk under the 2004 advisory addendum to the ATP III guidelines were included in the 16-week efficacy analysis. Switching to rosuvastatin significantly increased the proportion of these patients reaching the aggressive LDL-C target of <70 mg/dL compared with remaining on other statins in all treatment groups (Table IV).

Table IV. Goal achievement in subgroups at 16 weeks

Changes in other lipids and lipoproteins 

At 8 weeks, rosuvastatin 20 mg improved most lipid measures significantly more than atorvastatin 10 or 20 mg or simvastatin 20 or 40 mg (Table II). At 16 weeks, switching to rosuvastatin resulted in greater reductions in atherogenic lipid measures and ratios compared with remaining on either atorvastatin or simvastatin (all within-treatment arm comparisons P < .001) (Table III).

LDL-C, non–HDL-C, and apo B target achievement in hypertriglyceridemic patients 

Significantly greater percentages of hypertriglyceridemic patients reached the dual LDL-C and non–HDL-C targets with rosuvastatin than with equal or higher doses of atorvastatin or simvastatin (Table IV). Meeting the additional proposed apo B target was more difficult: less than half of the patients who could attain the dual LDL-C and non–HDL-C targets could meet all 3 targets (LDL-C, non–HDL-C, and apo B). In contrast, although the fraction of hypertriglyceridemic high-risk patients who attained the single target apo B of <90 mg/dL was small in all treatment groups, every patient who met this single target also attained the LDL-C and non–HDL-C targets. Thus, the numbers of patients who met all 3 targets are identical to those who met the apo B target alone. More patients met all 3 targets with rosuvastatin 10 mg than with atorvastatin 10 mg or simvastatin 20 mg and with rosuvastatin 20 mg than with atorvastatin 20 mg or simvastatin 40 mg (Table IV).

Safety 

All study treatments were well tolerated, with a low incidence of discontinuation. The frequency and type of adverse events were comparable among all treatment groups in both study periods (Table V, Table VI, Table VII, Table VIII). Serum CK elevations >10 times ULN occurred in 5 patients (Table VII, Table VIII); only 1 of these patients had muscle symptoms (bilateral leg cramps), a patient receiving rosuvastatin 20 mg in period 2 (1 [0.14%] of 740 patients receiving rosuvastatin 20 mg). Treatment was discontinued in this patient, with CK elevation resolving after discontinuation. No rhabdomyolysis was observed in any treatment arm.

Table V. Patients with at least 1 adverse event in period 1

Table VI. Patients with at least 1 adverse event in period 2

Table VII. Muscle, hepatic, and renal adverse events in period 1

Table VIII. Muscle, hepatic, and renal adverse events in period 2

There were no symptomatic adverse events indicative of hepatic dysfunction. One patient had alanine aminotransferase elevations >3 times ULN on 2 consecutive measurements (Table VII, Table VIII). The first measurement occurred during simvastatin 40 mg treatment in period 1 and the second during rosuvastatin 20 mg treatment in period 2. No patient had doubling of serum creatinine from baseline. The frequency of creatinine >30% from baseline was similar between periods and among treatment groups and ranged from 0% (period 1, atorvastatin 20 mg) to 1.3% (period 1, atorvastatin 10 mg). For patients with follow-up measurements (20/23), all but 2 of these increases (one patient on atorvastatin 10 mg and one on rosuvastatin 10 mg) either never exceeded normal limits or recovered while on continued therapy. Overall, serum creatinine showed a mean decrease of 2.8% (SD 9.96) to 3.8% (SD 9.60) from baseline to week 16 among treatment groups, with no apparent differences among groups. Shifts in urine protein from none or trace at baseline to ≥++ occurred in 9 (0.5%) of 1697 evaluated patients during period 1, with incidence ranging from 0% (atorvastatin 10 mg) to 1.2% (atorvastatin 20 mg). Such shifts occurred in 10 (0.6%) of 1608 patients evaluated in period 2, with rates ranging from 0% (simvastatin 40 mg) to 1.2% (simvastatin 20 mg). None of the increases in proteinuria were associated with renal impairment.

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Discussion 

Achievement of LDL-C targets in high-risk patients has been a challenging objective in clinical practice,⁸ particularly with the recommendation of even lower targets in very high risk patients based on evidence of clinical benefit.¹, ², ³, ⁹, ¹⁰ The LDL-C target of <100 mg/dL in high-risk patients and the optional LDL-C target of <70 mg/dL in very high risk patients are beyond the scope of many older-generation statins even with maximum doses in patients with elevated LDL-C. This study examined the 3 most effective statins at their starting or moderate doses,⁵ representing over three quarters of the dosages prescribed in clinical practice.¹¹ Results showed how difficult it is for some of these regimens to achieve the recommended or optional LDL-C targets.

High-risk hypertriglyceridemic patients have dual lipid targets: LDL-C <100 mg/dL (primary) and non–HDL-C <130 mg/dL (secondary). In these patients, an alternative secondary apo B target of <90 mg/dL might be representative of the dual lipid targets.³ This study shows that the two alternatives are not equivalent. Achieving an apo B of <90 mg/dL in patients with elevated TG was much more difficult than achieving both LDL-C <100 mg/dL and non–HDL-C <130 mg/dL. Conversely, achieving an apo B of <90 mg/dL guaranteed achieving the dual LDL-C and non–HDL-C targets.

Switching from statins that are less effective in reducing LDL-C, particularly when they are approaching their maximal dose, to those that are more effective in their lower dose range constitutes an important treatment option for optimizing achievement of ATP III goals in high-risk patients. This trial showed that switching from the most commonly used doses of atorvastatin or simvastatin to rosuvastatin at the recommended starting dose (10 mg) or optional starting dose (20 mg) is an effective strategy for improving LDL-C and non–HDL-C target achievement. Switching to rosuvastatin also led to greater achievement of the proposed apo B target in hypertriglyceridemic patients. The magnitude of the benefit achieved with switching to rosuvastatin in these high-risk patients is consistent with treatment differences observed in comparative trials of rosuvastatin and other statins at commonly used doses.⁵, ¹²

In this study, there were no clinically relevant differences among the statins in adverse events or propensity for causing skeletal muscle toxicity, hepatic impairment, or renal dysfunction over the relatively short duration of treatment. Similar safety findings have been reported in other comparative trials involving rosuvastatin and other statins at currently approved doses,¹², ¹³, ¹⁴, ¹⁵ and in long-term follow-up studies of rosuvastatin patients.¹⁶ Adding to the documented efficacy and safety of the 10-mg start dose, the data in this large trial reinforce that rosuvastatin 20 mg is an effective and safe therapeutic option for patients who need to achieve their lipid and apolipoprotein targets.

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We thank Joe Hirsch, from BioScience Communications, who provided medical writing support on behalf of AstraZeneca.

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