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Keywords:

  • statins;
  • systematic review;
  • therapeutic equivalence

Summary

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

Background:  Statins are the most commonly prescribed 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 efficacy 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 randomized 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 predetermined 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 performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins.

Results:  Seventy-five studies reporting RCTs of head-to-head comparisons on statins were included. Most studies had similar baseline characteristics, 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.


Background

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

Several large clinical trials had identified low density lipoprotein cholesterol (LDL-C) as one of the major predictors of coronary heart disease (CHD). Every 30 mg/dL (or 0·78 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, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin. All have a similar therapeutic effect (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, randomized, 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 approximately equivalent doses of statins to reduce LDL in head-to-head trials and found that all the commonly-used statins could reduce LDL by 20–30% or more (6). The Oregon Health Resources Commission (OHRC) carried out a systematic review of statins, and concluded that all statins could reduce LDL by up to 40% and elevate high-density lipoprotein (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 therapeutically 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 equivalent 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.

Methods

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

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 Collaboration (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 Chinese 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?

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, myopathy, 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 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 4·2 (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 taking the difference of means from each study and combing the differences after weighting the difference by sample size of each study. Heterogeneity between studies was assessed with the Cochrane Q-test, where a P-value of <0·10 suggests possibly 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

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

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 paired comparisons extracted from the 75 included studies. (Table 1).

Table 1.   Baseline characteristics of statin studies with paired-comparisons
  Studies includeda Studies with blindingb Pt (N)c Age ranged (years)Average study duration (weeks) (range)Baseline LDL-C (mg/dL) (range) Studies of Be
  1. aThere 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.

  2. bNumber of studies with blinded design.

  3. cSum of patients included in each paired comparison.

  4. dRange of age in each paired comparison.

  5. eNumber of paired comparisons where the study quality was evaluated as ‘B’ or above.

Atorvastatin vs.
 Fluvastatin5 [E21-3,26-7]0305018–8041·2 (8–54)195·7 (173–244)0
 Lovastatin7 [E1,21-3,25-7]1432418–8040·3 (8–54)197·5 (173–244)1 [E1]
 Pravastatin16 [E2-4,23-7,55-6,59-62,67,71]613 303>1833·1 (4–104)182·1 (121–247)7 [E2,4,55-6,60-1,67]
 Simvastatin31 [E5-27,55-6,59,65-6,69,71,75]1130 44818–8030·3 (4–250)175·8 (139–194)8 [E5,17-8,55-6,65-6,69]
 Rosuvastatin16 [E50-6,59,63-4,68,70-2,74-5]712 814>1815·8 (6–52)175·8 (139–194)8 [E50-1,53-6,68,72]
Fluvastatin vs.
 Lovastatin8 [E21-3,26-30]1264318–8028·3 (6–54)192·9 (173–244)1 [E30]
 Pravastatin4 [E23,26-7,31]1122718–8028·5 (8–54)205·7 (176–244)1 [E31]
 Simvastatin9 [E21-3,26-7,32-4,73]4228718–8027·3 (6–54)203·0 (173–267)2 [E32,34]
 Rosuvastatin000NoneNoneNone0
Lovastatin vs.
 Pravastatin8 [E23,25-7,35-8]4261418–8020·5 (4–54)200·0 (176–244)3 [E35-7]
 Simvastatin8 [E21-3,25-7,39-40]2254418–8034·0 (8–54)205·5 (173–291)2 [E39,40]
 Rosuvastatin000NoneNoneNone0
Pravastatin vs.
 Simvastatin20 [E23-7,41-9,55-9,71]106937>1817·0 (4–54)207·7 (164–314)10 [E43-8,55-8]
 Rosuvastatin6 [E55-59,71]34790>1818·3 (6–52)176·9 (164–194)4 [E55-8]
Simvastatin vs.
 Rosuvastatin7 [E55-9,71,75]36009>1817·4 (6–52)179·7 (165–194)4 [E55-8]

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 allocation. 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.

image

Figure 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 28·9–42.

Download figure to PowerPoint

From eyeballing the summarized data in Fig. 1, it was determined tentatively that 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 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 aggregated 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 comparing pravastatin 40 mg to simvastatin 10 mg (P = 0·07). Most of the differences between statins in lipid-lowering effects at the specified doses were small. For example, while the comparisons involving simvastatin 10 mg and other statins found some statistically significant differences, the differences were <7% and might not have significant implications in clinical practice.

Table 2.   Low density lipoprotein (LDL) reduction (%) of different statins in different doses
LDL reduction (%)Atorvastatin (mg)Fluvastatin (mg)Lovastatin (mg)Pravastatin (mg)Rosuvastatin (mg)Simvastatin (mg)
>40>20>5>40
30–40108040/8020
20–304010/2020/4010
<202010
Table 3.   Weighted mean difference (WMD) with 95% confidence interval (CI) of different statins at equivalent dose
Statin 1Statin 2 Studies included (N) Total Pt. (N)WMDa (statin 1–statin 2) % (95% C.I.) Heterogeneity testb
  1. aWMD (weighted mean difference) is the difference between statin 1 and statin 2 in the specified outcome, weighted by sample size of each study.

  2. bHeterogeneity between studies was assessed with the Cochrane Q-test where a P-value of <0·10 suggests possibly non-ignorable heterogeneity.

LDL[DOWNWARDS ARROW]30–40%
 Atorvastatin 10 mgLovastatin 40 mg1 [E23]897·00 [2·87, 11·13]None
 Atorvastatin 10 mgLovastatin 80 mg1 [E23]84−10·00 [−15·25, −4·75]None
 Atorvastatin 10 mgSimvastatin 20 mg11 [E8,10-11,14-15,20,23,55,59,71,75]50752·17 [1·20, 3·14]0·43
 Fluvastatin 80 mgLovastatin 80 mg1 [E27]52−9·00 [−17·01, −0·99]None
 Fluvastatin 80 mgSimvastatin 20 mg1 [E73]94−4·00 [−10·15, 2·15]None
 Lovastatin 40 mgSimvastatin 20 mg2 [E23,39]334−3·61 [−5·73, −1·48]0·85
 Lovastatin 80 mgSimvastatin 20 mg1 [E23]6013·00 [7·36, 18·64]None
LDL[DOWNWARDS ARROW]20–30%
 Fluvastatin 40 mgLovastatin 10 mg1 [E30]3341·00 [−1·70, 3·70]None
 Fluvastatin 40 mgLovastatin 20 mg3 [E23,28,30]496−4·81 [−7·25, −2·36]0·77
 Fluvastatin 40 mgPravastatin 20 mg2 [E23,31]179−0·38 [−3·89, 3·13]0·82
 Fluvastatin 40 mgPravastatin 40 mg2 [E23,27]87−9·37 [−14·50, −4·24]0·45
 Fluvastatin 40 mgSimvastatin 10 mg2 [E23,32]300−4·01 [−4·77, −3·26]0·76
 Lovastatin 20 mgPravastatin 20 mg4 [E23,25,27,35]393−1·10 [−3·05, 0·86]0·30
 Lovastatin 20 mgPravastatin 40 mg1 [E23]41−5·00 [−12·28, 2·28]None
 Lovastatin 20 mgSimvastatin 10 mg6 [E21-23,25-26,39]1773−3·50 [−4·70, −2·31]0·22
 Pravastatin 20 mgSimvastatin 10 mg5 [E23-25,E46,E55]945−3·87 [−4·62, −3·12]0·96
 Pravastatin 40 mgSimvastatin 10 mg2 [E23,55]4212·27 [0·31, 4·23]0·07

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 simvastatin 20 mg in reducing the risk of non-fatal myocardial infarction, peripheral arterial disease, and coronary revascularization (13).

Table 4.   Effects on cardiovascular events
Study All cause mortality (%) Myocardial infarction (%)Coronary heart disease death (%) Hospitalization for unstable angina (%) Revascularization (%) Stroke (%) Peripheral arterial disease (%)
  1. *The difference was significant at P < 0·05.

IDEAL
 Atorvastatin 80 mg vs. simvastatin 20 mg8·2 vs. 8·46·0 vs. 7·2*3·9 vs. 4·04·4 vs. 5·313·0 vs. 16·7*3·4 vs. 3·92·9 vs. 3·8*
PROVE-IT
 Atorvastatin 80 mg vs. pravastatin 40 mg2·2 vs. 3·26·6 vs. 7·41·1 vs. 1·43·8 vs. 5·1*16·3 vs. 18·8*1·0 vs. 1·0Not available

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 statins 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.

Table 5.   Incidence of specific adverse effects (%)
Statin [study included (n)]AtorvastatinFluvastatinLovastatinPravastatinSimvastatinRosuvastatin
  1. aMuscle toxicity included myalgia, myopathy, rhabdomyolysis, and the muscle-related symptoms.

  2. bCreatine kinase (CK) elevation >10 times upper limit of normal value (ULN).

  3. cALT/AST elevation >3 times ULN.

Muscle toxicitya0·01–9 [30]3–4 [3]1–9 [6]0·7–7·1 [12]0·4–4 [18]0·8–11 [15]
CK abnormalb0–0·63 [8]0 [0]0 [0]0 [2]0–0·3 [3]0·15–3·9 [7]
ALT/AST abnormalc0·1–7·3 [20]0·2–7·4 [3]0–1·4 [4]0·2–2·5 [7]0–1·7 [11]0·14–4·4 [8]

Discussion

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

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 insufficient 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 atorvastatin, simvastatin, and pravastatin under various doses. The results showed that there was no significant 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 systematic 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 systematic reviews by the VHA (6) and the OHRC (7).

To our knowledge the PROVE-IT and IDEAL trials were the only two clinical trials that had compared the CHD-prevention effect of different statins. However, the doses of various statins in these two trials are not therapeutically equivalent and therefore 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 on randomized placebo-controlled trials also compared the relative efficacy of atorvastatin, pravastatin, 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 toxicity 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 rosuvastatin 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 rosuvastatin 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

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

There are inherent variations among RCT reviewed in this study, possibly because of the fact that these trials were not aimed at establishing the therapeutically equivalent dose of different statins. The limited number of head-to-head studies also prevents us from carrying out a meaningful comparison on the lipid-lowering effect of some statins and on severe adverse events and long-term CHD-prevention for all the statins.

Conclusions

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

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 triglyceride-lowering effects are similar among different 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

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

We thank Shu-Wen Jia and Ching-Lan Cheng for their assistance in analysing the data.

References

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  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices
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  • 12
    Cannon CP, Braunwald E, McCabe CH et al. (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. New England Journal of Medicine, 350, 14951504.
  • 13
    Pedersen TR, Faergeman O, Kastelein JJP et al. (2005) High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA: The Journal of the American Medical Association, 294, 24372445.
  • 14
    Jones P, Kafonek S, Laurora I, Hunninghake D (1998) Comparative dose efficacy study of atorvastatin vs. simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). American Journal of Cardiology, 81, 582587.
  • 15
    Jones PH, Davidson MH, Stein EA et al. (2003) Comparison of the efficacy and safety of rosuvastatin vs. atorvastatin, simvastatin, and pravastatin across doses (STELLAR* trial). American Journal of Cardiology, 92, 152160.
  • 16
    Zhou Z, Rahme E, Abrahamowicz M et al. (2005) Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect. CMAJ: Canadian Medical Association Journal, 172, 11871194.
  • 17
    Silva MA, Swanson AC, Gandhi PJ, Tataronis GR (2006) Statin-related adverse events: a meta-analysis. Clinical Therapeutics, 28, 2635.
  • 18
    Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH (2005) The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation, 111, 30513057.
  • 19
    Davidson MH, Clark JA, Glass LM, Kanumalla A (2006) Statin safety: an appraisal from the adverse event reporting system. American Journal of Cardiology, 97, 32C43C.
  • 20
    Jacobson TA (2006) Statin safety: lessons from new drug applications for marketed statins. American Journal of Cardiology, 97, 44C51C.

Appendices

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Conclusions
  9. Acknowledgements
  10. References
  11. Appendices

Appendix

  • image(1)

[  Flow chart of the article selection. ]

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