Journal of Clinical Pharmacy and Therapeutics (2010) 35, 139–151
REVIEW ARTICLE
A systematic review and meta-analysis on the therapeutic
equivalence of statins
T.-C. Weng* MSc (Clin Pharm) , Y.-H. Kao Yang* BSPharm , S.-J. Lin PhD and
S.-H. Tai MSc (Clin Pharm)
*Institute of Clinical Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan,
Department of Pharmacy Administration, College of Pharmacy, University of Illinois at Chicago, Chicago,
IL, USA and Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan
SUMMARY
Background: Statins are the most commonly pre-
scribed agents for hypercholesterolemia because
of their efficacy and tolerability. As the number of
patients in need of statin therapy continues to
increase, information regarding the relative effi-
cacy and safety of statins is required for decision-
making.
Objective: This study will use systematic review
to compare the efficacy and safety profiles of
different statins at different doses and determine
the therapeutically equivalent doses of statins to
achieve a specific level of low-density lipoprotein
cholesterol (LDL-C) lowering effect.
Methods: Publications of head-to-head rando-
mized controlled trials (RCTs) of statins were
retrieved from the Oregon state database (1966–
2004), MEDLINE (2005-April of 2006), EMBASE
(2005-April of 2006), and the Cochrane Controlled
Trials Registry (up to the first quarter of 2006).
The publications were evaluated with pre-
determined criteria by a reviewer before they
were included in the review. The mean change in
cholesterol level of each statin was calculated and
weighted by number of subjects involved in each
RCT. Where possible, meta-analysis was per-
formed to generate pooled estimates of the cho-
lesterol lowering effect of statins and the
difference between statins.
Received 10 August 2008, Accepted 23 March 2009
Correspondence: Prof. Yea-Huei Kao Yang, Institute of Clinical
Pharmacy, College of Medicine, National Cheng Kung Uni-
versity, No.1, University Rd., Tainan 70101, Taiwan. Tel: +886 6
2353535 (5680); fax: +886 6 2373149; e-mail: yhkao@mail.ncku.
edu.tw
 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd
doi:10.1111/j.1365-2710.2009.01085.
Results: Seventy-five studies reporting RCTs of
head-to-head comparisons on statins were inclu-
ded. Most studies had similar baseline character-
istics, except the rosuvastatin related studies. A
daily dose of atorvastatin 10 mg, fluvastatin 80 mg,
lovastatin 40–80 mg, and simvastatin 20 mg could
decrease LDL-C by 30–40%, and fluvastatin 40 mg,
lovastatin 10–20 mg, pravastatin 20–40 mg, and
simvastatin 10 mg could decrease LDL-C by
20–30%. The only two statins that could reduce
LDL-C more than 40% were rosuvastatin and
atorvastatin at a daily dose of 20 mg or higher.
Meta-analysis indicated a statistically significant
but clinically minor difference (<7%) between
statins in cholesterol lowering effect. Comparisons
of coronary heart disease prevention and safety
could not be made because of insufficient data.
Conclusions: At comparable doses, statins are
therapeutically equivalent in reducing LDL-C.
Keywords: statins, systematic review, therapeutic
equivalence
BACKGROUND
Several large clinical trials had identified low den-
sity lipoprotein cholesterol (LDL-C) as one of the
major predictors of coronary heart disease (CHD).
Every 30 mg ⁄ dL (or 0Æ78 mmol ⁄ L) change in LDL-C
could increase the relative risk of CHD by 30% (1).
HMG CoA reductase inhibitors, also known as
statins, are considered first-line drugs to prevent
CHD because of their potent LDL-C lowering effect
(2). Currently there are six statins commonly
used for this indication, including lovastatin, sim-
vastatin, pravastatin, fluvastatin, atorvastatin, and
rosuvastatin. All have a similar therapeutic effect
139
140 T.-C. Weng
(class effect). However, the differences in their
chemical structures, pharmacokinetics, and relative
efficacy in lipid-lowering led to the question of their
therapeutic equivalence. In 2001, cerivastatin was
withdrawn from the market because of its unusually
high incidence of rhabdomyolysis relative to other
statins. The fact that cerivastatin was the only statin
removed from the market suggests that maybe not
all statins have equivalent safety profiles (3, 4).
Although the efficacy of individual statins has
been demonstrated in several large clinical trials,
there have been very few reports that summarized
their head-to-head trials and lipid-lowering effects.
A previous meta-analysis used an indirect method
to compare their effects in 164 short-term, ran-
domized, placebo-controlled trials at various doses
(5). The results showed that all the statins could
achieve a desirable LDL-lowering effect. Only two
review articles summarize head-to-head trials of the
statins. A review article from the Veterans Health
Administration (VHA) identified the approxi-
mately equivalent doses of statins to reduce LDL in
head-to-head trials and found that all the com-
monly-used statins could reduce LDL by 20–30% or
more (6). The Oregon Health Resources Commis-
sion (OHRC) carried out a systematic review of
statins, and concluded that all statins could reduce
LDL by up to 40% and elevate high-density lipo-
protein (HDL) to a similar level at equipotent doses
(7). However, neither the VHA nor the OHRC used
statistical methods to summarize the effects of the
statins or specifically determined the therapeuti-
cally equivalent doses of statins.
Since the publication of the VHA and OHRC
reviews, more randomized controlled trials (RCTs)
comparing statins have been reported (E61-E75).
The primary objectives of this systematic review
are to incorporate the recent RCT in previous
reviews and to perform a meta-analysis to compare
the effects of six commonly-used statins at different
doses. The estimates of the therapeutically equiv-
alent doses of statins should provide guidance for
clinicians when switching or tapering statins in
their clinical practices. This study also aimed to
compare the safety profile of statins, especially
with respect to muscle and liver toxicities, and
long-term cardiovascular outcomes. Sensitivity
analyses were performed to compare results by
including either all RCT or only those that reached
a predetermined level of quality.
 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
METHODS
Formulating the problem
The specific research questions of this study are:
1. What are the therapeutically equivalent doses of
statins in modifying lipid profiles, including
lowering LDL-C and triglycerides and elevating
HDL cholesterol (HDL-C)?
2. Is the ability to prevent CHD similar among
statins?
3. Are there differences between statins in the
incidence of liver and muscle toxicities?
Locating RCT studies
Clinical trials published between 1966 and Apr.
2006 (when the current study was initiated),
including those previously reviewed by OHRC
(7) (before Jan. 2005) and the newer trials indexed
by PubMed ⁄ Medline (Jan. 2005–Apr. 2006),
EMBASE (Jan. 2005–Apr. 2006), and Cochrane
Controlled Trials Registry (first quarter of 2006),
as well as those listed in the references of each
retrieved article were investigated. The search
strategy of the electronic databases was consistent
with the one used in a previous systematic
review (7) and suggested by the Cochrane Col-
laboration (8).
Selecting studies
Only those RCTs with head-to-head comparisons
were included. Trials that were not based on human
subjects, did not report primary data, lasted
<4 weeks, or were not published in English or Chi-
nese were excluded. Eligible patients were those over
18 years old who used statins as a monotherapy for
hyperlipidemia.
Quality assessment of studies
Quality of RCTs was evaluated with four criteria
previously suggested (7–10):
1. Was the assignment of subjects to the study
groups random?
2. Was the random assignment concealed?
3. Were the patients, outcome assessors, and care
providers blinded?
4. Was the attrition rate similar between different
groups during the follow-up period?
 Therapeutic equivalence of statins 141

The criteria were used to assign a grade of ‘A’ to
‘E’ to each study, ‘A’ being the best and ‘E’ the worst.
A study would be graded ‘A’ if it met all four criteria,
‘B’ if one of the criteria was not met or unable to be
judged, and so forth. If none of the criteria was met
in a study, a grade of ‘E’ was assigned.
Collecting data
Data collected were type of study design, study
duration, number and baseline characteristics of
patients, type of statin and dosage used, and the
resultant changes in lipid profile. For long-term
studies, the incidence of CHD was collected. The
adverse events considered were myalgia, myopa-
thy, rhabdomyolysis (taken ‘as is’ because of the
lack of uniform definitions of the three terms
among studies) (11), creatine kinase (CK) levels 10
times the upper limit of normal value (ULN), and
AST ⁄ ALT values three times the ULN. Microsoft
Excel was used to summarize data and produce the
evidence tables.
Statistical analysis
To determine the therapeutically equivalent doses of
statins, we first determined specific ranges of LDL-C
reduction (i.e. reduce LDL 30–40% and 20–30%) that

Table 1. Baseline characteristics of statin studies with paired-comparisons

Average study Baseline

Studies Age duration LDL-C
Studies with ranged (weeks) (mg ⁄ dL) Studies
includeda blindingb Pt (N)c (years) (range) (range) of Be

Atorvastatin vs.
Fluvastatin 5 [E21-3,26-7] 0 3050 18–80 41Æ2 (8–54) 195Æ7 (173–244) 0
Lovastatin 7 [E1,21-3,25-7] 1 4324 18–80 40Æ3 (8–54) 197Æ5 (173–244) 1 [E1]
Pravastatin 16 [E2-4,23-7,55-6, 6 13 303 >18 33Æ1 (4–104) 182Æ1 (121–247) 7 [E2,4,55-6,
59-62,67,71] 60-1,67]
Simvastatin 31 [E5-27,55-6,59, 11 30 448 18–80 30Æ3 (4–250) 175Æ8 (139–194) 8 [E5,17-8,55-6,
65-6,69,71,75] 65-6,69]
Rosuvastatin 16 [E50-6,59,63-4, 7 12 814 >18 15Æ8 (6–52) 175Æ8 (139–194) 8 [E50-1,53-6,
68,70-2,74-5] 68,72]
Fluvastatin vs.
Lovastatin 8 [E21-3,26-30] 1 2643 18–80 28Æ3 (6–54) 192Æ9 (173–244) 1 [E30]
Pravastatin 4 [E23,26-7,31] 1 1227 18–80 28Æ5 (8–54) 205Æ7 (176–244) 1 [E31]
Simvastatin 9 [E21-3,26-7,32-4,73] 4 2287 18–80 27Æ3 (6–54) 203Æ0 (173–267) 2 [E32,34]
Rosuvastatin 0 0 0 None None None 0
Lovastatin vs.
Pravastatin 8 [E23,25-7,35-8] 4 2614 18–80 20Æ5 (4–54) 200Æ0 (176–244) 3 [E35-7]
Simvastatin 8 [E21-3,25-7,39-40] 2 2544 18–80 34Æ0 (8–54) 205Æ5 (173–291) 2 [E39,40]
Rosuvastatin 0 0 0 None None None 0
Pravastatin vs.
Simvastatin 20 [E23-7,41-9, 10 6937 >18 17Æ0 (4–54) 207Æ7 (164–314) 10 [E43-8,55-8]
55-9,71]
Rosuvastatin 6 [E55-59,71] 3 4790 >18 18Æ3 (6–52) 176Æ9 (164–194) 4 [E55-8]
Simvastatin vs.
Rosuvastatin 7 [E55-9,71,75] 3 6009 >18 17Æ4 (6–52) 179Æ7 (165–194) 4 [E55-8]

a
There were 75 head-to-head studies included: 62 studies compared two different statins, four studies compared three different statins, six
studies compared four different statins, and three studies compared five different statins. There were 140 paired comparisons altogether.
b
Number of studies with blinded design.
c
Sum of patients included in each paired comparison.
d
Range of age in each paired comparison.
e
Number of paired comparisons where the study quality was evaluated as ‘B’ or above.

 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
142 T.-C. Weng

Fig. 1. Comparisons of the lipid lowering effect of different statins. (1) The point estimate indicates the weighted-
average of pooled analysis, and the vertical bar shows the range of lipid-lowering effects of the included studies. (2) The
horizontal axis is composed of drug labels, indicating the specific statin and dose studied. A, F, L, P, S, and R stand for
atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and rosuvastatin, respectively, whereas the number after
the single alphabet represents the dose used. For examples, A10 is atorvastatin 10 mg and S20 is simvastatin 20 mg.
Under each drug label is the number of head-to-head comparisons involving the specific dose and statin. To illustrate,
the first panel [low-density lipoprotein (LDL)-lowering effect] shows that 31 clinical trials with atorvastatin 10 mg
reported the drug could reduce LDL by 28Æ9–42.

most statins can achieve. For statins and doses that
have been reported in previous RCTs to achieve
similar ranges in LDL reduction, meta-analyses were
performed with Review Manager 4Æ2 (8) to aggregate
across the RCTs and compare the specific statins and
doses in their LDL- and triglyceride-lowering and
HDL-elevating effects. The fixed-effect weighted
mean difference (WMD) with 95% confidence
intervals was used as the summary statistic. WMD is
a method of combining measures on continuous
scales [e.g. decrease (%) in cholesterol level] by tak-
ing the difference of means from each study and
combing the differences after weighting the differ-
ence by sample size of each study. Heterogeneity
between studies was assessed with the Cochrane
Q-test, where a P-value of <0Æ10 suggests possibly

 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
 Therapeutic equivalence of statins 143

Table 2. Low density lipoprotein (LDL) reduction (%) of different statins in different doses

LDL Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin

reduction (%) (mg) (mg) (mg) (mg) (mg) (mg)

>40 >20 – – – >5 >40

30–40 10 80 40 ⁄ 80 – – 20
20–30 – 40 10 ⁄ 20 20 ⁄ 40 – 10
<20 – 20 – 10 – –

non-ignorable heterogeneity (8). Adverse events of
statins (muscle and liver toxicities) and the long-term
effect of statins on incidence of CHD at equivalent
doses were also compared.
RESULTS
Study characteristics
Around 3587 potentially relevant articles published
after 2005 were identified. After perusing the titles
and abstracts, 3524 articles were excluded, whereas
63 full-text articles were retrieved for further
evaluation. Among the full-text articles retrieved,
48 were deemed unsuitable (see figure in appendix
for details). The remaining 15 were combined with
the 60 trials previously reviewed by OHRC to
perform this systematic review. A list of the 75
trials (E1-E75) can be found in the appendix. Some
studies reported more than one head-to-head
comparison of statins, which lead to a total of 140

Table 3. Weighted mean difference (WMD) with 95% confidence interval (CI) of different statins at equivalent dose

WMDa
Studies Total Pt. (statin 1–statin 2) % Heterogeneity
Statin 1 Statin 2 included (N) (N) (95% C.I.) testb

LDLfl30–40%
Atorvastatin 10 mg Lovastatin 40 mg 1 [E23] 89 7Æ00 [2Æ87, 11Æ13] None
Atorvastatin 10 mg Lovastatin 80 mg 1 [E23] 84 )10Æ00 [)15Æ25, )4Æ75] None
Atorvastatin 10 mg Simvastatin 20 mg 11 [E8,10-11, 5075 2Æ17 [1Æ20, 3Æ14] 0Æ43
14-15,20,23,
55,59,71,75]
Fluvastatin 80 mg Lovastatin 80 mg 1 [E27] 52 )9Æ00 [)17Æ01, )0Æ99] None
Fluvastatin 80 mg Simvastatin 20 mg 1 [E73] 94 )4Æ00 [)10Æ15, 2Æ15] None
Lovastatin 40 mg Simvastatin 20 mg 2 [E23,39] 334 )3Æ61 [)5Æ73, )1Æ48] 0Æ85
Lovastatin 80 mg Simvastatin 20 mg 1 [E23] 60 13Æ00 [7Æ36, 18Æ64] None
LDLfl20–30%
Fluvastatin 40 mg Lovastatin 10 mg 1 [E30] 334 1Æ00 [)1Æ70, 3Æ70] None
Fluvastatin 40 mg Lovastatin 20 mg 3 [E23,28,30] 496 )4Æ81 [)7Æ25, )2Æ36] 0Æ77
Fluvastatin 40 mg Pravastatin 20 mg 2 [E23,31] 179 )0Æ38 [)3Æ89, 3Æ13] 0Æ82
Fluvastatin 40 mg Pravastatin 40 mg 2 [E23,27] 87 )9Æ37 [)14Æ50, )4Æ24] 0Æ45
Fluvastatin 40 mg Simvastatin 10 mg 2 [E23,32] 300 )4Æ01 [)4Æ77, )3Æ26] 0Æ76
Lovastatin 20 mg Pravastatin 20 mg 4 [E23,25,27,35] 393 )1Æ10 [)3Æ05, 0Æ86] 0Æ30
Lovastatin 20 mg Pravastatin 40 mg 1 [E23] 41 )5Æ00 [)12Æ28, 2Æ28] None
Lovastatin 20 mg Simvastatin 10 mg 6 [E21-23,25-26,39] 1773 )3Æ50 [)4Æ70, )2Æ31] 0Æ22
Pravastatin 20 mg Simvastatin 10 mg 5 [E23-25,E46,E55] 945 )3Æ87 [)4Æ62, )3Æ12] 0Æ96
Pravastatin 40 mg Simvastatin 10 mg 2 [E23,55] 421 2Æ27 [0Æ31, 4Æ23] 0Æ07

a
WMD (weighted mean difference) is the difference between statin 1 and statin 2 in the specified outcome, weighted by sample size of
each study.
b
Heterogeneity between studies was assessed with the Cochrane Q-test where a P-value of <0Æ10 suggests possibly non-ignorable
heterogeneity.

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144 T.-C. Weng

paired comparisons extracted from the 75 included
studies. (Table 1).
Most studies had similar baseline characteristics,
except the rosuvastatin-related studies, which tend
to have a lower baseline level in LDL-C and a
shorter study-period. All the included trials used
randomization design, but only three included or
reported an appropriate method to conceal alloca-
tion. The attrition rate of most trials was similar
between the comparison groups. Based on the
grading criteria, 51 studies (68%) were judged to
have a quality level of B or better in the internal
validity assessment.
Comparisons of lipid-lowering effects
The lipid-lowering effects of different statins in
various doses are showed in Fig. 1. The general
trend is that the effect on reduction of LDL-C
increases with the dose of the statins, albeit not in a
linear fashion. A sensitivity analysis, by including
only those trials that were graded as ‘B’ or better in
internal validity, found similar aggregated effects
and smaller variance between studies (data not
shown). All the following results were based on the
75 studies.
From eyeballing the summarized data in Fig. 1, it
was determined tentatively that atorvastatin 10 mg,
fluvastatin 80 mg, lovastatin 40–80 mg, and sim-
vastatin 20 mg could decrease LDL-C by 30–40%,
and fluvastatin 40 mg, lovastatin 10–20 mg, pra-
vastatin 20–40 mg, and simvastatin 10 mg could
reduce LDL-C by 20–30%. Rosuvastatin at 10 mg or
higher dose and atorvastatin at 20 mg or higher dose
could reduce LDL-C by more than 40% (Table 2).
Studies involving statins and doses that could
decrease LDL-C by 30–40% or 20–30% were aggre-
gated by meta-analysis. Table 3 shows the WMD
and 95% confidence intervals of the percentage of
LDL-C reduction by different statins at equivalent
doses. The heterogeneity test was not significant for
most paired comparisons, except for studies com-
paring pravastatin 40 mg to simvastatin 10 mg
(P = 0Æ07). Most of the differences between statins in

Table 4. Effects on cardiovascular events

Coronary
All cause Myocardial heart Hospitalization Peripheral
mortality infarction disease for unstable Revascularization Stroke arterial
Study (%) (%) death (%) angina (%) (%) (%) disease (%)

IDEAL
Atorvastatin 80 mg 8Æ2 vs. 8Æ4 6Æ0 vs. 7Æ2* 3Æ9 vs. 4Æ0 4Æ4 vs. 5Æ3 13Æ0 vs. 16Æ7* 3Æ4 vs. 3Æ9 2Æ9 vs. 3Æ8*
vs. simvastatin 20 mg
PROVE-IT
Atorvastatin 80 mg 2Æ2 vs. 3Æ2 6Æ6 vs. 7Æ4 1Æ1 vs. 1Æ4 3Æ8 vs. 5Æ1* 16Æ3 vs. 18Æ8* 1Æ0 vs. 1Æ0 Not available
vs. pravastatin 40 mg

*The difference was significant at P < 0Æ05.

Table 5. Incidence of specific adverse effects (%)

Statin [study included (n)] Atorvastatin Fluvastatin Lovastatin Pravastatin Simvastatin Rosuvastatin

Muscle toxicitya 0Æ01–9 [30] 3–4 [3] 1–9 [6] 0Æ7–7Æ1 [12] 0Æ4–4 [18] 0Æ8–11 [15]
CK abnormalb 0–0Æ63 [8] 0 [0] 0 [0] 0 [2] 0–0Æ3 [3] 0Æ15–3Æ9 [7]
ALT ⁄ AST abnormalc 0Æ1–7Æ3 [20] 0Æ2–7Æ4 [3] 0–1Æ4 [4] 0Æ2–2Æ5 [7] 0–1Æ7 [11] 0Æ14–4Æ4 [8]

a
Muscle toxicity included myalgia, myopathy, rhabdomyolysis, and the muscle-related symptoms.
b
Creatine kinase (CK) elevation >10 times upper limit of normal value (ULN).
c
ALT ⁄ AST elevation >3 times ULN.

 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151

lipid-lowering effects at the specified doses were
small. For example, while the comparisons involv-
ing simvastatin 10 mg and other statins found some
statistically significant differences, the differences
were <7% and might not have significant implica-
tions in clinical practice.
Some statins had a limited number of head-to-
head comparisons. For example, in the group
which reduced LDL-C by 20–30%, there was only
one trial each for fluvastatin 40 mg vs. lovastatin
10 mg and lovastatin 20 mg vs. pravastatin 40 mg.
In the group with 30–40% reduction in LDL-C,
only two-paired comparisons (simvastatin 20 mg
vs. atorvastatin 10 mg and simvastatin 20 mg vs.
lovastatin 40 mg) have been investigated in more
than 1 RCT. The limited number of head-to-head
RCTs precluded the possibility of performing
meta-analysis for some statins and ⁄ or doses. In
LDL reduction, at equivalent doses the selected
statins did not show significant differences in their
effects on HDL and TG.
Comparisons for prevention of coronary heart
disease
There were only two RCTs comparing statins in
CHD prevention (Table 4). One was the PROVE-IT
trial, which found that atorvastatin 80 mg provided
greater protection against unstable angina and
revascularization than pravastatin 40 mg (12). The
other was the IDEAL trial, where atorvastatin
80 mg appeared to be more effective than sim-
vastatin 20 mg in reducing the risk of non-fatal
myocardial infarction, peripheral arterial disease,
and coronary revascularization (13).
Comparisons of adverse events
The incidence of muscle toxicity was rare in all the
included trials (Table 5). Even when all the muscle-
related symptoms were considered, the rate was still
<10%. However, the studies involving rosuvastatin
generally reported a higher adverse event rate than
the other comparison arms. When these studies were
excluded, the muscle-related adverse events of sta-
tins decreased to around 5% (data not shown). Only
the studies involving atorvastatin, rosuvastatin, and
simvastatin observed an increased CK level 10 times
the ULN. The incidence of elevated ALT ⁄ AST level
(i.e. three times the ULN) was <1% in most trials.
 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
Therapeutic equivalence of statins 145
DISCUSSION
In contrast to most previous studies, this study
quantified the differences and similarities of statins,
including efficacy and safety, assessed in head-
to-head comparison trials, and provided pooled
estimates where possible. The quantitative results of
the lipid-lowering effect of each statin could serve as
a quick guide for clinicians. This study identifies
heterogeneity among studies and areas with insuf-
ficient data where future studies could be focused.
Our results show that, in general, the reduction
in LDL-C increases with the dose of the statin, and
equivalent doses could be found for most statins to
achieve the commonly targeted levels of LDL-C.
The HDL-C-elevation and TG-reduction effects
were also similar among statins. Previously, two
large clinical trials have compared multiple statins
at the same time. The CURVES study compared
efficacy between atorvastatin and other statins in
patients with hypercholesterolemia and found
atorvastatin 10 mg to produce an LDL-C reduction
comparable to lovastatin 80 mg, pravastatin 40 mg,
and simvastatin 20–40 mg (14). In the STELLAR
study, rosuvastatin was compared with atorvasta-
tin, simvastatin, and pravastatin under various
doses. The results showed that there was no sig-
nificant difference between rosuvastatin 10–20 mg
and atorvastatin 20, 40, or 80 mg in their effect on
lowering LDL-C (15). After including more head-
to-head trials and summarizing them with sys-
tematic review and meta-analysis, we found the
therapeutic equivalent doses of statins were similar
to that of the CURVES and STELLAR trials. Our
results are also consistent with two earlier sys-
tematic reviews by the VHA (6) and the OHRC (7).
To our knowledge the PROVE-IT and IDEAL tri-
als were the only two clinical trials that had com-
pared the CHD-prevention effect of different statins.
However, the doses of various statins in these two
trials are not therapeutically equivalent and there-
fore might not be appropriate for comparing the
long-term effect between the statins. Previously, a
retrospective cohort study used data from medical
administrative databases of Canada to compare the
effectiveness of statins for secondary prevention
after myocardial infarction (16). The results showed
that atorvastatin, fluvastatin, lovastatin, pravastatin,
and simvastatin had similar effects on elderly
patients with this indication. A meta-analysis based
146 T.-C. Weng
on randomized placebo-controlled trials also com-
pared the relative efficacy of atorvastatin, pravasta-
tin, and simvastatin and found no significant
difference between the three statins in preventing
CHD when used in the standard doses (4).
We were unable to evaluate the difference
between statins on incidence of muscle or liver tox-
icity because of insufficient data. One previous meta-
analysis evaluated the overall adverse event data
(including myalgia, any CK or AST ⁄ ALT change,
and any adverse event) reported in RCTs and found
atorvastatin to be associated with the greatest risk of
adverse events and fluvastatin to have the least risk
among all statins (17). An observational study by
Alsheikh-Ali (18), using first-year post-marketing
data, found the total of rhabdomyolysis, proteinuria,
nephropathy, and renal-failure events of rosuvast-
atin to appear higher than that of other statins. More
clinical trials are needed to compare adverse events
such as myopathy or abnormal AST ⁄ ALT and to
exclude the possibility that the seemingly higher
rates of adverse events in atorvastatin and rosu-
vastatin might be due to ‘new drug effect’; a bias
because of newer drugs being scrutinized much
more than older drugs and therefore more adverse
events being detected (19, 20).
LIMITATIONS
There are inherent variations among RCT reviewed
in this study, possibly because of the fact that these
trials were not aimed at establishing the thera-
peutically equivalent dose of different statins. The
limited number of head-to-head studies also pre-
vents us from carrying out a meaningful compari-
son on the lipid-lowering effect of some statins and
on severe adverse events and long-term CHD-
prevention for all the statins.
CONCLUSIONS
Statins can be made therapeutically equivalent in
reducing LDL by appropriate adjustment of dose.
Atorvastatin 10 mg, fluvastatin 80 mg, lovastatin
40 ⁄ 80 mg, and simvastatin 20 mg are equivalent
in decreasing LDL-C by 30–40%; and fluvastatin
40 mg, lovastatin 10 ⁄ 20 mg, pravastatin 20 ⁄ 40 mg,
and simvastatin 10 mg were similar in reducing
LDL-C by 20–30%. The HDL-elevating and tri-
glyceride-lowering effects are similar among dif-
 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
ferent statins at equivalent doses. The current
data are not sufficient to determine the relative
safety of the different statins or their relative
effectiveness in CHD-prevention.
ACKNOWLEDGEMENTS
We thank Shu-Wen Jia and Ching-Lan Cheng for
their assistance in analysing the data.
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APPENDIX

3587 articles published after 2005 were selected from electronic databases
(PubMed, EmBASE, Cochrane Controlled Trails Registry.)

3524 articles were excluded after

reviewing the title and abstract.

63 full-text articles retrieved

48 articles were excluded.
for more detailed evaluation.
36 articles were not randomized comparative
studies.
10 articles were not reporting primary data.
2 articles did not collect the needed outcomes.

Total 15 statins comparative

studies were included.

Total 75 statins
comparative studies.

OHRC database
60 statins comparative
studies were included.

Fig. 1. Flow chart of the article selection.

 2009 The Authors. Journal compilation  2009 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 139–151
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