ORIGINAL ARTICLE

DOI: 10.3904/kjim.2010.25.1.27

Comparative Study of Low Doses of Rosuvastatin and

Atorvastatin on Lipid and Glycemic Control in Patients with
Metabolic Syndrome and Hypercholesterolemia
Jong-Seon Park1, Young-Jo Kim1, Ji-Yong Choi2, Yoon-Nyun Kim3, Teck-Jong Hong4, Dong-Soo Kim5,
Ki-Young Kim6, Myung-Ho Jeong7, Jei-Keon Chae8, Seok-Kyu Oh9, and In-Whan Seong10

Departments of Internal Medicine, 1Yeungnam University Medical Cencer, Daegu; 2Daegu Catholic University Medical Center,
Daegu; 3Keimyung University Dongsan Medical Center, Daegu; 4Pusan National University Hospital, Busan; 5Inje University
Pusan Paik Hospital, Busan; 6Konyang University Hospital, Daejeon; 7Chonnam National University Hospital, Gwangju;
8
Chonbuk National University Hospital, Jeonju; 9Wonkwang University Hospital, Iksan; 10Chungnam National University
Hospital, Daejeon, Korea

Background/Aims: This multicenter, open-labeled, randomized trial was performed to compare the effects of
rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic
metabolic syndrome.
Methods: In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment
Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels
≥ 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for
over 6 weeks.
Results: After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 ± 11.38 vs. - 30.07 ± 10.46%,
p < 0.001), LDL-C (48.04 ± 14.45 vs. 39.52 ± 14.42%, p < 0.001), non-high-density lipoprotein cholesterol
(- 42.93 ± 13.15 vs. - 35.52 ± 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 ± 18.85 vs. - 32.57 ± 17.56%, p =
0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the
percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin
(87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of
insulin resistance index were not significantly different between the two groups. The safety and tolerability of the
two agents were similar.
Conclusions: Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C
goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level
goals. (Korean J Intern Med 2010;25:27-35)

Keywords: Metabolic syndrome X; Hypercholesterolemia; Rosuvastatin; Atorvastatin

INTRODUCTION cardiovascular disease [1]. Using the modified National

Cholesterol Education Program (NCEP) Expert Panel on
Metabolic syndrome consists of a group of cardiovascular Detection, Evaluation, and Treatment of High Blood
risk factors, namely dyslipidemia, high blood pressure Cholesterol in Adults (Adult Treatment Panel III [ATP
(BP), abdominal obesity, and insulin intolerance, whose III]) criteria, the prevalence of atherosclerotic cardiovascular
concurrent appearance increases the risk of atherosclerotic disease is estimated to be as high as 24.8% in Korea and is

Received: May 3, 2009

Accepted: July 21, 2009

Correspondence to Young-Jo Kim, M.D., Ph.D.

Department of Internal Medicine, Yeungnam University Medical Cencer, 317-1 Daemyung-dong, Nam-gu, Daegu 705-717, Korea
Tel: 82-53-620-3833, Fax: 82-53-654-8386, E-mail: [email protected]
28 The Korean Journal of Internal Medicine Vol. 25, No. 1, March 2010

Figure 1. Trial design. LDL, low-density lipoprotein; HDL, high-density lipoprotein.

continuing to rapidly increase to epidemic proportions atorvastatin 10 mg, which are the lowest-dose tablets
[2]. Elevated cholesterol levels have also been shown to be available, on the percentage of patients who reach the
a strong risk factor for the development of coronary heart NCEP ATP III LDL-C goal and safety in subjects with
disease (CHD). This clustering of risk factors may interact nondiabetic metabolic syndrome after 6 weeks of
synergistically to affect atherosclerosis and cardiovascular treatment. The secondary objective was to compare the
events [3]. Current guidelines for lipid management stress effects of rosuvastatin with that of atorvastatin on glucose
the importance of low-density lipoprotein cholesterol control and insulin resistance.
(LDL-C) levels as the primary goal of therapy [4]; however,
a high proportion of patients, especially those having high
lipid levels, do not achieve their target LDL-C levels METHODS
despite lipid-lowering therapy [5,6].
Statins effectively lower blood cholesterol levels and Study design
reduce the risk of cardiovascular events in many patient This 6-week, multicenter, randomized, open-label,
types, and are therefore recommended as first-line agents parallel-group, single-dose trial (NCT00335699) was
for lowering LDL-C levels [4,7]. Statins also improve other designed to compare the efficacy of a single dose of
aspects of the lipid profile, such as increasing high-density rosuvastatin and atorvastatin in patients having nondiabetic
lipoprotein cholesterol (HDL-C) and lowering triglyceride metabolic syndrome with dyslipidemia (Fig. 1). The study
levels to some extent. was conducted from August 2005 to January 2006 at 20
Rosuvastatin is a highly effective HMG-CoA reductase medical centers in Korea. The study included a 6-week
inhibitor, which was registered in 2002 in Korea. dietary run-in period before randomization, followed by a
Rosuvastatin use has been previously shown in numerous 6-week treatment phase. Subjects entering the run-in
studies to be associated with greater LDL-C level reductions period were asked to follow the NCEP Step I diet and
as compared to atorvastatin, simvastatin, or pravastatin required to discontinue any previous lipid lowering therapy.
use [8-10]. The primary objective of the current trial was Following the dietary lead-in period, patients with fasting
to compare the effects of rosuvastatin 10 mg with that of LDL-C levels ≥ 130 mg/dL to < 220 mg/dL were selected
 Park JS, et al. Comparison of rosuvastatin and atorvastatin in metabolic syndrome 29

Table 1. Baseline characteristics at randomization

Factors Rosuvastatin 10 mg Atorvastatin 10 mg p value

(n = 172) (n = 178)

Sex, male, % 73 (42.44) 67 (37.64) 0.359

Age, yr 60.49 ± 0.74 58.96 ± 0.75 0.148
Weight, kg 66.84 ± 0.81 66.73 ± 0.83 0.924
Height, cm 160.01 ± 0.75 158.80 ± 0.64 0.221
Systolic BP, mmHg 134.58 ± 1.15 135.73 ± 1.14 0.477
Diastolic BP, mmHg 80.16 ± 0.78 80.18 ± 0.82 0.988
Waist circumference, cm 91.81 ± 0.47 91.60 ± 0.54 0.760
Values are presented as the mean ± SE.
BP, blood pressure.

Table 2. Changes in metabolic parameters after treatment

Rosuvastatin 10 mg Atorvastatin 10 mg p value c

(n = 170) (n=176)
Baseline Treatment Baseline Treatment

Lipids, mg/dL
Total cholesterol 237.52 ± 2.07 151.70 ± 2.26 b 238.55 ± 1.89 166.23 ± 2.01 b < 0.0001
LDL-C 163.64 ± 1.76 84.37 ± 1.81 b 163.85 ± 1.62 98.37 ± 1.76 b < 0.0001
HDL-C 39.66 ± 0.54 39.15 ± 0.55 39.76 ± 0.55 38.55 ± 0.57 a 0.448
Triglyceride 171.08 ± 5.20 140.92 ± 4.64 b 174.75 ± 4.69 146.56 ± 4.76 b 0.397
Non-HDL-C 197.85 ± 1.90 112.55 ± 2.12 b 198.80 ± 1.77 127.69 ± 1.88 b < 0.0001
Apolipoprotein A-1 141.95 ± 2.01 141.65 ± 1.76 141.75 ± 1.92 140.71 ± 2.43 0.756
Apolipoprotein B 117.44 ± 1.55 71.12 ± 1.69 b 117.90 ± 1.38 78.62 ± 1.50 b 0.001
Glucose and insulin
Glucose, mg/dL 91.08 ± 0.75 91.07 ± 0.95 93.32 ± 0.84 91.86 ± 0.88 0.541
HbA1c, % 5.88 ± 0.04 5.93 ± 0.04 a 5.86 ± 0.03 5.86 ± 0.03 0.456
HOMA index 1.21 ± 0.07 1.57 ± 0.11 a 1.52 ± 0.18 1.45 ± 0.11 0.465
hsCRP, mg/L 2.29 ± 0.30 2.24 ± 0.42 a 2.23 ± 0.35 1.77 ± 0.26 a 0.344
Values are presented as the mean ± SE.
LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA1c, hemoglobin A1C; HOMA, homeostasis
model assessment; hsCRP, high-sensitivity C-reactive protein.
a p < 0.05 vs. baseline.
b p < 0.001 vs. baseline.
c Statistical difference between rosuvastatin and atorvastatin after treatment.

and randomly assigned to two parallel treatment groups. this study.

At baseline, eligible subjects were randomized 1 : 1 to
receive either rosuvastatin (Astra-Zeneca Korea, Seoul, Subjects
Korea) 10 mg or atorvastatin (Pfizer Pharmaceuticals Patients were ≥ 18 years of age and had nondiabetic
Korea, Seoul, Korea) 10 mg once daily at bedtime for 6 metabolic syndrome. Metabolic syndrome was defined
weeks. The study drug was discontinued and subjects according to the modified NCEP ATP III criteria [11],
were removed from the study if they withdrew informed which requires at least three of the following: abdominal
consent, became pregnant, or developed creatine kinase obesity (waist circumference): men > 90 cm (36 inches),
levels greater than 10 times the upper normal limit. women > 80 cm (32 inches); triglyceride levels ≥ 150
The ethics committees and institutional review boards mg/dL (1.70 mmol/L); HDL-C levels: men < 40 mg/dL
at each participating hospital approved the study protocol. (1.04 mmol/L) and women < 50 mg/dL (1.3 mmol/L); BP
All patients provided informed consent to participate in ≥ 130 / ≥ 85 mmHg or subject receiving antihypertensive
30 The Korean Journal of Internal Medicine Vol. 25, No. 1, March 2010

Figure 2. Percent change of lipid and apolipoprotein after

treatment for 6 weeks.
LDL-C, low-density lipoprotein cholesterol; Total-C, total
cholesterol; HDL-C, high-density lipoprotein cholesterol; Apo,
apolipoprotein. Figure 3. Proportions of patients reaching different Adult
Treatment Panel III, low-density lipoprotein cholesterol (LDL-
C) level goals at 6 weeks after treatment.
a Proportion of patients reaching LDL-C level goal < 100, 130 or
treatment; and fasting blood glucose 110 mg/dL (6.11 160 mg/dL depending on risk category at baseline.
mmol/L) to 125 mg/dL (6.94 mmol/L). Patients were
excluded if they were pregnant or had malignancy.
Additional exclusion criteria included diabetes, and active Friedewald equation (LDL-C = total cholesterol - (HDL-C
arterial disease such as unstable angina, myocardial + triglyceride/5). The insulin resistance index was
infarction, cerebrovascular accident, coronary artery estimated using the homeostasis model assessment
bypass surgery, or angioplasty within 2 months prior to (HOMA) for insulin resistance based on the following
enrollment. After completing the 6-week dietary run-in formula: fasting serum insulin (µU/mL) × fasting plasma
period, fasting LDL-C concentrations were required to be glucose (mmol/L)/22.5. According to the NCEP ATP III
≥ 130 mg/dL (3.36 mmol/L) to < 220 mg/dL (5.69 guidelines, the goal LDL-C level for each patient and the
mmol/L) and fasting triglyceride levels were required to proportion of patients achieving the goal in each group
be < 400 mg/dL (4.52 mmol/L). was assessed. Persons with CHD or CHD risk equivalent
(Framingham 10-year CHD risk > 20%) had a LDL-C
Assessments level goal of < 100 mg/dL. Those with multiple risk factors
Sample analysis for efficacy endpoints was performed in had a LDL cholesterol level goal of < 130 mg/dL and those
the Green Cross Reference Laboratory, Yongin, Korea, with 0 - 1 risk factor (s) had a goal LDL cholesterol of < 160
which was certified by the American College of Pathology mg/dL.
(LAP No. 6708401) and the National Committee for Individual demographic data, physical findings, vital
Clinical Laboratory Standards. Blood samples from signs, and adverse events were evaluated and recorded in
patients who had fasted for 12 hours were collected at all the given case record form. To evaluate adverse events,
investigational sites and delivered by courier to the central various laboratory assessments including blood counts,
laboratory within 24 hours of blood draw. To assess the and hemoglobin, aspartate aminotransferase, alanine
primary efficacy endpoint, lipid parameters such as total aminotransferase, creatine kinase, electrolyte, and creatinine
cholesterol, LDL-C, HDL-C, and triglyceride levels were levels were performed at each time point.
measured during the dietary lead-in period, at random-
ization, and 6 weeks after treatment. Additionally, levels of Statistical analysis
apolipoprotein A-1 and B, high-sensitivity C-reactive One-hundred and forty-three evaluable subjects per
protein (hsCRP), insulin, glucose, and hemoglobin A1c treatment group were required to achieve 95% power for
(HbA1c) were measured at randomization and at 6 weeks detecting a clinically significant difference of 6% at the 5%
after treatment. LDL-C levels were calculated using the two-sided level in percentage change from baseline in
 Park JS, et al. Comparison of rosuvastatin and atorvastatin in metabolic syndrome 31

Table 3. Percent change of glucose and insulin resistance after treatment for 6 weeks

Factors Rosuvastatin Atorvastatin p value

(n = 170) (n = 176)

Glucose 0.24 ± 0.84 - 1.12 ± 0.76 0.231

Insulin 68.14 ± 13.28 67.91 ± 18.20 0.992
HbA1c 1.08 ± 0.53 - 0.10 ± 0.28 0.048
HOMA index 69.79 ± 13.49 72.60 ± 20.84 0.910
Values are presented as the mean ± SE.
HbA1c, hemoglobin A1c; HOMA, homeostasis model assessment.

LDL-C levels at 6 weeks with an assumed standard of all 350 subjects who took at least one dose of the study
deviation of 14% [12]. Assuming a dropout rate of 20% drug at baseline. In terms of demographic data and baseline
during the randomized treatment period, approximately characteristics, no statistically significant differences
180 subjects were recruited to each active treatment existed between the two treatment groups. Patients had a
group. To obtain the required number of randomized mean age of 60 years in the rosuvastatin group and 58
subjects (360 in total), approximately 900 subjects were years in the atorvastatin group. Mean body weights were
assumed to be needed for screening based on a screening 66 kg in the rosuvastatin group and 66 kg in the atorvas-
failure rate of 60%. tatin group. Mean systolic and diastolic BP and waist
The primary analysis population was the last observation circumstance were comparable between the two groups
carried forward on the intention-to-treat population. This (Table 1).
included all subjects with a baseline and at least one post- A total of five patients dropped out before efficacy
baseline lipid level measurement. All numeric variables assessment. Data from 346 patients were analyzed for
were expressed as the mean ± SEM (standard error of the efficacy in the intention-to-treat population defined as
mean). Efficacy endpoints were analyzed using the those who took at least one dose of study drug and had
unpaired t-test for continuous variables and Pearson’s chi- lipid levels checked at baseline and follow-up. Safety
square test for frequencies with 95% confidence intervals. assessments were performed in 350 patients who were
Multivariate logistic regression analysis was used to randomized and available for follow-up.
evaluate the predictors for reaching target NCEP ATP III
LDL-C levels after treatment. Variables used for analysis Changes in metabolic parameters
included the statin used, presence of coronary artery disease Lipid levels, glucose levels, insulin resistance indices,
and hypertension, body mass index, gender, age, waist and hsCRP levels at baseline and 6 weeks are shown in
circumference, and lipid parameters. Table 2. In each group, atherogenic lipid parameters
On the basis of the actual treatment received, safety including total cholesterol, LDL-C, triglyceride, non-HDL-
data were evaluated for all patients who received at least C, and apolipoprotein B had significantly decreased after
one dose of study medication. 6 weeks of treatment (p < 0.001 vs. baseline). Only the
atorvastatin treatment produced a modest decrease in
HDL-C. Rosuvastatin treatment significantly increased
RESULTS HbA1c and the HOMA index; however, no significant
change occurred in the atorvastatin group.
Subject characteristics Data from two groups were analyzed for an efficacy
In total, 645 subjects were screened for participation in comparison in the intention-to-treat population. Baseline
this study. Of them, 370 patients entered the dietary lead- values of all parameters were similar between the two
in phase and 351 patients met the inclusion criteria and groups. At 6 weeks after treatment, rosuvastatin 10 mg
were randomly assigned to treatment with either produced a significantly greater reduction in total
rosuvastatin 10 mg or atorvastatin 10 mg (Fig. 1). One cholesterol, LDL-C, non-HDL-C, and apolipoprotein B
patient was lost to follow-up and had no safety assessment. levels. Otherwise, no significant differences were detected
Table 1 shows demographic data and baseline characteristics in HDL-C and apolipoprotein A-1 levels between the two
32 The Korean Journal of Internal Medicine Vol. 25, No. 1, March 2010

Table 4. Most common treatment-related adverse Framingham 10-year risk, the NCEP ATP III LDL-C target
events (≥ 1% in any treatment group) during the goal was determined in each patient and the success rate
treatment period in reaching their target goal was analyzed after 6 weeks in
Adverse events Rosuvastatin Atorvastatin each group.
(n = 172) (n = 178) The percentage of patients who reached their ATP III
Any adverse events 13 (7.56) 9 (5.06)
LDL-C level goals was higher in the rosuvastatin group
Serious adverse events 1 (0.58) 2 (1.12) (87.6 vs. 69.9%, p < 0.001). Among them, patients having
Drug related adverse events 0 (0.00) 5 (2.81) LDL-C target cholesterol level goals of < 100 mg and <
Adverse events which caused 130 mg reached their LDL-C target level goals more
0 (0.00) 1 (0.56)
discontinuation of the study frequently in the rosuvastatin group as compared to the
Values are presented as number (%). atorvastatin group. In contrast, in patients with a LDL-C
target level goal < 160 mg, more than 96% reached their
target goal without a significant difference between the
groups. In addition, no significant differences were rosuvastatin- and atorvastatin-treated groups (Fig. 3). The
observed with respect to glucose, HbA1c, and hsCRP overall achievement rate for NCEP non-HDL-C level
levels, and HOMA index between the rosuvastatin and target goals after 6 weeks of treatment was 76.08% in the
atorvastatin groups at 6 weeks (Table 2). At 6 weeks, LDL- rosuvastatin group and 58.92% in the atorvastatin group
C absolute values decreased by 48.04 ± 14.45 mg/dL in (p = 0.067).
the rosuvastatin group and by 39.52 ± 14.42 mg/dL in the
atorvastatin group; the former reduction associated with Percent changes in glucose levels and insulin
rosuvastatin use was significantly larger than that with resistance
atorvastatin (p < 0.0001).
Percent changes from baseline in lipid profiles after Percent changes in glucose levels and insulin resistance
treatment for 6 weeks, including LDL-C, are shown in Fig. at 6 weeks are summarized in Table 3. Changes in glucose
2. Reductions in total cholesterol (- 35.94 ± 11.38 vs. and insulin levels were not significantly different between
- 30.07 ± 10.46%, p < 0.0001), non-HDL-C (- 42.93 ± the two groups; however, HbA1c levels were slightly higher
13.15 vs. - 35.52 ± 11.76%, p < 0.0001), and apolipoprotein in the rosuvastatin group with marginal significance. To
B (- 38.7 ± 18.85 vs. - 32.57 ± 17.56%, p = 0.0019) levels evaluate insulin resistance in the two groups, the HOMA
were larger in the rosuvastatin group as compared to the index was calculated. At 6 weeks, the HOMA index increased
atorvastatin group (Fig. 2). in both groups and the difference between groups was not
significant.
LDL-C target achievement
According to the reported CHD or/and CHD risk Safety
equivalents and/or number of risk factors and/or Both rosuvastatin 10 mg and atorvastatin 10 mg were

Table 5. Adjusted odds ratios for LDL-cholesterol goal achievement after treatment for 6 weeks

Factors Odds ratio (95% confidence interval) Standard error p value

Age, yr 0.997 (0.966 - 1.029) 0.016 0.850

Sex, male 0.424 (0.214 - 0.842) 0.350 0.014
Hypertension 1.025 (0.434 - 2.421) 0.439 0.955
Coronary artery disease 3.806 (1.959 - 7.391) 0.339 < 0.001
Body mass index ≥ 25 0.669 (0.353 - 1.267) 0.326 0.217
Waist circumference > 90 cm 1.445 (0.703 - 2.968) 0.368 0.317
Total cholesterol ≥ 230 mg/dL 0.885 (0.390 - 2.006) 0.418 0.769
LDL-cholesterol ≥ 160 mg/dL 0.446 (0.208 - 0.960) 0.391 0.039
Treatment, rosuvastatin 3.26 (1.800 - 5.906) 0.303 < 0.001
LDL, low-density lipoprotein.
 Park JS, et al. Comparison of rosuvastatin and atorvastatin in metabolic syndrome 33

well tolerated, with similar incidences of adverse events. LDL-C levels, is already known to increase the risk of
During the treatment period, 13 subjects in the rosuvastatin cardiovascular mortality and morbidity [13]. Statins are
group and 9 subjects in the atorvastatin group reported effective in decreasing LDL-C levels in patients with
adverse events (Table 4). The most frequent adverse dyslipidemia. Survey studies have demonstrated that in
events in the rosuvastatin group were edema and dizziness, real-world settings, only 67% of patients with treated
both with incidences of 1.16%. Only five adverse events dyslipidemia reach their LDL-C target level goals [14]. In
were reported in the atorvastatin group as related to the this study, rosuvastatin treatment was associated with
study drug; myalgia was reported in one case (0.56%). All reaching recommended LDL-C level goals in a higher
adverse events were mild, developed within 2 weeks after percentage of patients overall as compared to atorvastatin
starting treatment, had no action taken, and resolved (87.6 vs. 69.9%). In particular, rosuvastatin was more
spontaneously. No drug-related adverse effects were effective in patients requiring more intensive LDL-C level
observed in the rosuvastatin group. Also, no patient had lowering to less than 100 or 130 mg/dL. In high-risk
an increase in alanine aminotransferase level > 3 times patients with stronger targets of LDL-C levels < 100
the upper limit of normal or rhabdomyolysis. mg/dL, rosuvastatin brought 83% of patients in this trial
to the ATP III LDL-C level goal, which was higher than
Predictors for LDL-C level goal achievement at 6 achieved in other studies conducted in South-Asian (76%)
weeks and Hispanic-American (61%) patients [15,16]. Both
Overall, the percentage of patients who reached NCEP statins, however, were effective in patients with high
ATP III LDL-C target level goals was higher in the target LDL-C level goals < 160 mg/dL. These data
rosuvastatin group as compared to the atorvastatin group. highlight the importance of using highly effective statins
Univariate analysis showed that patients with target in high-risk patients to enable them to achieve their lower
LDL-C levels at 6 weeks tended to be rosuvastatin-treated NCEP ATP III LDL-C level goals.
and have coronary artery disease. Multivariate logistic With respect to other elements of the lipid profile,
regression analyses that included age, gender, statin, improvements in total cholesterol, apolipoprotein B, and
coronary artery disease, hypertension, body mass index, non-HDL-C levels were also significantly greater with
waist circumference, baseline total cholesterol levels, and rosuvastatin as compared to atorvastatin, whereas changes
triglyceride levels showed that rosuvastatin treatment, the in HDL-C, triglyceride, and apolipoprotein A1 levels were
presence of coronary artery disease, female gender, lower similar in both treatment groups. Unlike other studies in
total cholesterol level, and lower LDL-C levels at baseline which rosuvastatin effectively raised HDL-C levels [9,15],
were independent predictors for achievement of target HDL-C levels in this study were not effectively improved
LDL-C levels at 6 weeks (Table 5). in either group [9].
Metabolic syndrome is associated with an increased risk
of both insulin resistance and diabetes [17]. Additionally,
DISCUSSION changes in the insulin resistance index were investigated
by evaluating the HOMA index, which is a positive predictor
This study evaluated the comparative efficacy of the of metabolic syndrome [18]. Studies in an animal model of
lowest doses available for two effective statins, rosuvastatin insulin resistance suggest that rosuvastatin treatment
and atorvastatin, in Korean patients with nondiabetic increases whole-body and peripheral tissue insulin
metabolic syndrome. sensitivity via improved cellular insulin signal transduction
Rosuvastatin 10 mg was more effective than atorvastatin [19]. In contrast, in our study conducted in nondiabetic
10 mg in reducing LDL-C levels in subjects with nondiabetic subjects, a tendency was detected for an increased HOMA
metabolic syndrome after 6 weeks of treatment. Consistent index in both treatment arms. Major changes in this
with the greater reductions in LDL-C levels, more patients parameter were attributable to high increases in insulin
in the rosuvastatin group achieved LDL-C level goals concentrations. The degrees of percent change in fasting
as compared to the atorvastatin group. Otherwise, no glucose, insulin concentrations, and HOMA index were
significant difference was observed in glucose levels and not significantly different between the rosuvastatin and
insulin resistance. atorvastatin treatment groups. Thus, further studies are
Metabolic syndrome, especially in the presence of high needed to elucidate the effects of statins on glucose
34 The Korean Journal of Internal Medicine Vol. 25, No. 1, March 2010

metabolism, insulin secretion, and insulin sensitivity Medical Center; Sung-Cheol Chae, Kyungpook National
under diabetic or nondiabetic conditions. University Hospital; Yoon-Nyun Kim, Keimyung University
A multivariate analysis was performed to determine Dongsan Medical Center; Teck-Jong Hong, Pusan National
independent predictors of LDL-C goal achievement at 6 University Hospital; Jae-Woo Lee, Kosin University Gospel
weeks. Overall, sex, the presence of coronary artery Hospital; Young-Dae Kim, Donga University Medical
disease, LDL-C levels, and rosuvastatin treatment were Center; Tae-Ik Kim, Maryknoll General Hospital; Dong-
predictive of target LDL-C achievement. Among these Soo Kim, Inje University Pusan Paik Hospital; Jin-Yong
factors, rosuvastatin was the strongest predictor, with an Hwang, Gyeongsang National University Hospital; Sang-
odds ratio of 3.26. Moreover, the presence of coronary Gon Lee, Ulsan University Hospital; Ki-Young Kim,
artery disease was an independent predictor of achieving Konyang University Hospital; Myung-Ho Jeong, Chonnam
target LDL-C levels. These patients were assumed to have National University Hospital; Seung-Uk Lee, Kwangju
been more likely to take interest in diet control or exercise Christian Hospital; Ok-Young Park, Seonam University
than patients without coronary artery disease. Hospital; Jei-Keon Chae, Chonbuk National University
Although the findings of this study are provocative, Hospital; Jay-Young Rhew, Jeonju Jesus Hospital; Seok-
this study has important limitations. Recently, intensive Kyu Oh, Wonkwang University Hospital; In-Whan Seong,
regimens with 80 mg of atorvastatin or 20 mg of rosuvastatin Chungnam National University Hospital; and Jang-Hyun
have become available in Korea and produce greater Cho, Suncheon Saint Carollo Hospital.
reductions in atherosclerotic lipoprotein levels, which is
particularly useful in patients with established coronary
artery disease or acute coronary syndrome. Further studies REFERENCES
comparing statins across dose ranges in patients not
reaching their target goal with low-dose statins are 1. Brewer HB Jr. New features of the National Cholesterol
required. Additionally, although changes metabolic Education Program Adult Treatment Panel III lipid-lowering
guidelines. Clin Cardiol 2003;26(4 Suppl 3):III19-III24.
parameters were not the primary endpoint of this study, a
2. Kwon HS, Park YM, Lee HJ, et al. Prevalence and clinical
trend toward differences in blood glucose levels was
characteristics of the metabolic syndrome in middle-aged Korean
observed between the two statins. Further studies are
adults. Korean J Intern Med 2005;20:310-316.
needed to elucidate the metabolic effects of statins. 3. Kim YK. Impact of the metabolic syndrome and its components
In conclusion, this study demonstrated that rosuvastatin on pulse wave velocity. Korean J Intern Med 2006;21:109-115.
10 mg is significantly more effective than atorvastatin 10 4. Boden WE. Therapeutic implications of recent ATP III guidelines
mg in reducing LDL-C levels in patients with nondiabetic and the important role of combination therapy in total dyslipidemia
metabolic syndrome, especially among those with lower management. Curr Opin Cardiol 2003;18:278-285.
NCEP ATP III target level goals. Both statins were well 5. Yood MU, McCarthy BD, Kempf J, et al. Racial differences in
reaching target low-density lipoprotein goal among individuals
tolerated.
treated with prescription statin therapy. Am Heart J 2006;152:
777-784.

Conflict of interest 6. Leibovitz E, Harats D, Gavish D. Efficacy of atorvastatin in

treating high risk patients to reach low density lipoprotein-
No potential conflict of interest relevant to this article cholesterol goals: the Treat to Target (TTT-Israel) Study. Isr Med
was reported. Assoc J 2002;4:407-410.
7. Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive summary of the third
Acknowledgements report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High
We gratefully acknowledge the investigators and study
Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA
coordinators, and the patients who participated in this
2001;285:2486-2497.
trial. We also thank AstraZeneca Korea, who funded this
8. McKenney JM, Jones PH, Adamczyk MA, et al. Comparison of
trial. the efficacy of rosuvastatin versus atorvastatin, simvastatin, and
The following investigators participated in this trial: pravastatin in achieving lipid goals: results from the STELLAR
Young-Jo Kim and Jong-Seon Park, Yeungnam University trial. Curr Med Res Opin 2003;19:689-698.
Hospital; Ji-Yong Choi, Daegu Catholic University 9. Clearfield MB, Amerena J, Bassand JP, et al. Comparison of the
 Park JS, et al. Comparison of rosuvastatin and atorvastatin in metabolic syndrome 35

efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg 15. Stalenhoef AF, Ballantyne CM, Sarti C, et al. A comparative study
in high-risk patients with hypercholesterolemia: prospective with rosuvastatin in subjects with metabolic syndrome: results of
study to evaluate the Use of Low doses of the Statins Atorvastatin the COMETS study. Eur Heart J 2005;26:2664-2672.
and Rosuvastatin (PULSAR). Trials 2006;7:35. 16. Deedwania PC, Gupta M, Stein M, Ycas J, Gold A. Comparison of
10. Ferdinand KC, Clark LT, Watson KE, et al. Comparison of efficacy rosuvastatin versus atorvastatin in South-Asian patients at risk of
and safety of rosuvastatin versus atorvastatin in African- coronary heart disease (from the IRIS Trial). Am J Cardiol 2007;
American patients in a six-week trial. Am J Cardiol 2006;97:229- 99:1538-1543.
235. 17. Grundy SM, Hansen B, Smith SC Jr, Cleeman JI, Kahn RA.
11. Choi SH, Ahn CW, Cha BS, et al. The prevalence of the metabolic Clinical management of metabolic syndrome: report of the
syndrome in Korean adults: comparison of WHO and NCEP American Heart Association/National Heart, Lung, and Blood
criteria. Yonsei Med J 2005;46:198-205. Institute/American Diabetes Association conference on scientific
12. Deedwania PC, Hunninghake DB, Bays HE, et al. Effects of issues related to management. Circulation 2004;109:551-556.
rosuvastatin, atorvastatin, simvastatin, and pravastatin on 18. Pivatto I, Bustos P, Amigo H, Acosta AM, Arteaga A. Association
atherogenic dyslipidemia in patients with characteristics of the between proinsulin, insulin, proinsulin/insulin ratio, and insulin
metabolic syndrome. Am J Cardiol 2005;95:360-366. resistance status with the metabolic syndrome. Arq Bras
13. Dekker JM, Girman C, Rhodes T, et al. Metabolic syndrome and Endocrinol Metabol 2007;51:1128-1133.
10-year cardiovascular disease risk in the Hoorn Study. Circulation 19. Naples M, Federico LM, Xu E, Nelken J, Adeli K. Effect of
2005;112:666-673. rosuvastatin on insulin sensitivity in an animal model of insulin
14. Davidson MH. Differences between clinical trial efficacy and real- resistance: evidence for statin-induced hepatic insulin sensitization.
world effectiveness. Am J Manag Care 2006;12(15 Suppl):S405- Atherosclerosis 2008;198:94-103.
S411.