Download Suggestion from clinicians

Simvastatin vs. Rosuvastatin vs. Atorvastatin
Replacement to the List
Peer Feedback:
“Most folks now favour using the high potency statins. Atorvastatin or rosuvastatin. Suggest replacing
simvastatin with these.”
“same interactions as atorva, rosuva more potent LDL lowering, simva 80 mg is not recommended"
Rosuvastatin was also suggested as an addition:
“One of the more commonly used statins”
Note: Atorvastatin is on the list.
Literature Review Question:
Which of Rosuvastatin, atorvastatin and simvastatin is the most efficacious?
Literature Search:
Cochrane Review Search of each drug
Pubmed: ‘rosuvastatin AND atorvastatin AND simvastatin AND efficacy AND comparison’
Pubmed: ‘rosuvastatin AND simvastatin AND efficacy AND comparison’
eCPS - Cardiovascular Disorders: Dyslipidemias
Atorvastatin Cochrane Review (2015)
In this update, we found an additional 42 trials and added them to the original 254 studies. The update
consists of 296 trials that evaluated dose-related efficacy of atorvastatin in 38,817 participants. Included
are 242 before-and-after trials and 54 placebo-controlled RCTs. Log dose-response data from both trial
designs revealed linear dose-related effects on blood total cholesterol, LDL-cholesterol, HDL-cholesterol
and triglycerides. The Summary of findings table 1 documents the effect of atorvastatin on LDLcholesterol over the dose range of 10 to 80 mg/d, which is the range for which this systematic review
acquired the greatest quantity of data. Over this range, blood LDL-cholesterol is decreased by 37.1% to
51.7% (Summary of findings table 1). The slope of dose-related effects on cholesterol and LDLcholesterol was similar for atorvastatin and rosuvastatin, but rosuvastatin is about three-fold more potent.
Subgroup analyses suggested that the atorvastatin effect was greater in females than in males and was
greater in non-familial than in familial hypercholesterolaemia. Risk of bias for the outcome of withdrawals
due to adverse effects (WDAEs) was high, but the mostly unclear risk of bias was judged unlikely to affect
lipid measurements. Withdrawals due to adverse effects were not statistically significantly different
between atorvastatin and placebo groups in these short-term trials (risk ratio 0.98, 95% confidence
interval 0.68 to 1.40).
This update resulted in no change to the main conclusions of the review but significantly increases the
strength of the evidence. Studies show that atorvastatin decreases blood total cholesterol and LDLcholesterol in a linear dose-related manner over the commonly prescribed dose range.New findings
include that atorvastatin is more than three-fold less potent than rosuvastatin, and that the
cholesterollowering effects of atorvastatin are greater in females than in males and greater in non-familial
than in familial hypercholesterolaemia. This review update does not provide a good estimate of the
incidence of harms associated with atorvastatin because included trials were of short duration and
adverse effects were not reported in 37% of placebo-controlled trials.
Adams, Stephen P., Michael Tsang, and James M. Wright. "Lipid lowering efficacy of atorvastatin." The Cochrane
Library (2012).
Rosuvastatin Cochrane review 2014
One-hundred and eight trials (18 placebo-controlled and 90 before-and-after) evaluated the dose-related
efficacy of rosuvastatin in 19,596 participants. Rosuvastatin 10 to 40 mg/day caused LDL-cholesterol
decreases of 46%to 55%, when all the trials were combined using the generic inverse variance method.
The quality of evidence for these effects is high. Log dose-response data over doses of 1to 80 mg,
revealed strong linear dose-related effects on blood total cholesterol, LDL-cholesterol and non-HDLcholesterol. When compared to atorvastatin, rosuvastatin was about three-fold more potent at reducing
LDL-cholesterol. There was no dose-related effect of rosuvastatin on blood HDL-cholesterol, but overall,
rosuvastatin increased HDL by 7%. There is a high risk of bias for the trials in this review, which would
affect WDAEs, but unlikely to affect the lipid measurements. WDAEs were not statistically different
between rosuvastatin and placebo in 10 of 18 of these short-term trials (risk ratio 0.84; 95% confidence
interval 0.48 to 1.47).
The total blood total cholesterol, LDL-cholesterol and non-HDL-cholesterol-lowering effect of rosuvastatin
was linearly dependent on dose. Rosuvastatin log dose-response data were linear over the commonly
prescribed dose range. Based on an informal comparison with atorvastatin, this represents a three-fold
greater potency. This review did not provide a good estimate of the incidence of harms associated with
rosuvastatin because of the short duration of the trials and the lack of reporting of adverse effects in
44%of the placebo-controlled trials.
Adams, Stephen P., Sarpreet S. Sekhon, and James M. Wright. "Lipid‐lowering efficacy of
rosuvastatin." The Cochrane Library (2014).
Rosuvastatin vs Atorvastatin, Pravastatin, and Simvastatin. 2014
More recently, various studies7,18 reported that patients with MetS had greater reductions in TG and
somewhat greater percentage increases in HDL-C with statin treatment, as expected. The comparisons
between statin treatment groups showed consistent advantages of rosuvastatin treatment, compared with
atorvastatin, simvastatin, and pravastatin, in LDL-C goal achievement and in LDL-C, total cholesterol, and
non-HDL-C reduction. As in the main study analysis, rosuvastatin 10 mg provided benefits comparable to
a higher dose of atorvastatin in the MetS population. It is worth noting that a pharmacoeconomic analysis
of the primary MERCURY results7,18 showed that treatment with rosuvastatin 10 mg was more costeffective compared with equivalent or higher doses of atorvastatin, simvastatin, and pravastatin, and that
switching patients from a comparator statin to rosuvastatin improved LDL-C goal attainment at relatively
little additional cost, with equivalent (or lower) associated drug costs.7,18 Thus, rosuvastatin may have
pharmacoeconomic advantages, compared with atorvastatin, while providing comparable efficacy.
Finally, rosuvastatin at a low dose has demonstrated high efficacy for LDL-C lowering, enabling patients
with hypercholesterolemia to achieve their lipid goals.13,18 In addition, rosuvastatin has beneficial effects
on other components of the lipid profile, including HDL-C,13,24-27 which is a major, independent risk
factor for CVD.8,25 Safety data from several large-scale clinical and pharmacoepidemiologic studies
have shown that the safety of rosuvastatin25-27 and results from the current recent study also support
these findings.19
Bener, Abdulbari, et al. "Comparison of Cost-Effectiveness, Safety, and Efficacy of Rosuvastatin Versus
Atorvastatin, Pravastatin, and Simvastatin in Dyslipidemic Diabetic Patients With or Without Metabolic
Syndrome." Journal of primary care & community health 5.3 (2014): 180-187.
Mckenney et al 2003
The STELLAR trial is the largest trial of its kind to date to compare dose-related effects of statins on lipid
goal achievement in patients with hypercholesterolemia. Trial results indicate that rosuvastatin 10 to 40
mg has greater efficacy than atorvastatin 10 to 80 mg, simvastatin 10 to 80 mg, and pravastatin 10 to 40
mg for achievement of ATP III LDL-C and non-HDL-C goals, European LDL-C goals, and Canadian LDLC and triple goals (which also included total cholesterol/HDL-C ratio and triglyceride goals). It is
particularly noteworthy that with rosuvastatin therapy, more patients achieve the most aggressive LDL-C
goals of < 100 mg/dl (< 2.6 mmol/l) and < 116 mg/dl (< 3.0 mmol/l), regardless of CHD risk status. This
greater goal-attaining efficacy of rosuvastatin is due in large part to its greater efficacy in lowering LDL-C,
as shown previously (Figure 7)14. Rosuvastatin 10 mg reduced LDL-C by 46%, which was significantly
greater ( p < 0.002) than the 37% reduction achieved with atorvastatin 10 mg, the 28% to 39% reductions
achieved with simvastatin 10 to 40 mg, and the 20% to 30% reductions achieved with pravastatin 10 to 40
mg14. In the rosuvastatin 40-mg group, LDL-C was reduced by 55%, compared with 48% for atorvastatin
40 mg ( p < 0.002), 51% for atorvastatin 80 mg ( p = 0.006, NS), 39% for simvastatin 40 mg ( p < 0.002),
46% for simvastatin 80 mg ( p < 0.002), and 30% for pravastatin 40 mg ( p < 0.002)14.
In summary, more patients treated with rosuvastatin 10 to 40mg achieved lipid goals, and optimal LDL-C
levels as suggested by the NCEP ATP III and European guidelines, than patients treated with
atorvastatin, simvastatin, and pravastatin. The proportions of patients in the rosuvastatin 10-mg group
who reached the LDL-C level of < 100 mg/dl (< 2.6 mmol/l), both the non-HDL-C and LDL-C goals, and
the Canadian LDL-C goals were significantly greater ( p < 0.002) than the proportions in the atorvastatin
10-mg, simvastatin 10-, 20-, and 40-mg, and pravastatin 10-, 20-, and 40-mg groups. The highest
proportions of patients who achieved NCEP ATP III, European, and Canadian goals were in the
rosuvastatin groups.
McKenney, James M., et al. "Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin,
and pravastatin in achieving lipid goals: results from the STELLAR trial." Current Medical Research and
Opinion® 19.8 (2003): 689-698.
eCPS (2014)
Class
Drug
HMG-CoA
Reductase
Inhibitors
atorvastatin
Lipitor,
generics
HMG-CoA
Reductase
Inhibitors
rosuvastatin
Crestor,
generics
Administer
antacids 2 h
after
rosuvastatin.
HMG-CoA
Reductase
Inhibitors
simvastatin
Zocor,
generics
Adverse Effects
Drug Interactions
Adults: 10–80
mg daily po at
any time of day
Children:b 10–
20 mg daily po
Common: Increased CK,
Increased transaminases
(reversible), mild upper GI
disturbances, myalgias (with and
without CK elevation), sleep
disturbances, headache, rash.
Rare: myopathy,
rhabdomyolysis, peripheral
neuropathy, lupus-like
symptoms, impotence.
Avoid with CYP3A4 inhibitors:
amiodarone, azoles,
cyclosporine, gemfibrozil,
grapefruit juice, macrolide
antibiotics, nondihydropyridine
calcium channel blockers,
e.g., verapamil, protease
inhibitors.
Common: Increased CK,
Increased transaminases
(reversible), mild upper GI
disturbances, myalgias (with and
without CK elevation), sleep
disturbances, headache, rash.
Rare: myopathy,
rhabdomyolysis, peripheral
neuropathy, lupus-like
symptoms, impotence.
Avoid with CYP2C9 inhibitors:
amiodarone, fluconazole,
fluoxetine, fluvoxamine.
Reduced levels with
Contraindications: active
concomitant use of
liver disease, high alcohol
magnesium/aluminum
consumption, pregnancy.
hydroxide-containing antacids.
$
Common: Increased CK,
Increased transaminases
(reversible), mild upper GI
disturbances, myalgias (with and
without CK elevation), sleep
disturbances, headache, rash.
Rare: myopathy,
rhabdomyolysis, peripheral
neuropathy, lupus-like
symptoms, impotence.
Avoid with CYP3A4 inhibitors:
amiodarone, azoles,
cyclosporine, gemfibrozil,
grapefruit juice, macrolide
antibiotics, nondihydropyridine
calcium channel blockers,
e.g., verapamil, protease
inhibitors.
$
Adults: 10–40
mg daily po
Initial dose 10
mg/day po
except in Asian
patients and
those receiving
cyclosporine
(initial dose 5
mg/day po)
Comments
Costa
Dose
Start with low doses and
$
titrate up to reach targets
while monitoring
biochemical markers.
Liver function (ALT)
should be checked at least
once at 3 months. Check
CK if myalgia develops.
Use caution in patients
with moderate to severe
renal impairment(<60
mL/min).
Children:b 5–10
mg daily po
Adults: 10–80
mg po with
evening meal
Children:b 10–
40 mg po with
evening meal
Cardiovascular Disorders: Dyslipidemias; Ghislaine O. Roederer, MD, PhD; Date of revision: June 2014
Medication
simvastatin
atorvastatin
Uses
Contraindications (CI), drug
interactions (DI) or cautions
Hyperlipidemia,
coronary artery
disease, heart
failure
CI: active liver disease, alcohol and
pregnancy
hyperlipidemia,
coronary artery
disease, heart
failure
CI: active liver disease, alcohol, pregnancy
DI: CPY-3A4, digoxin, warfarin,
clarithromycin, erythromycin, gemfibrozil,
grapefruit juice, verapamil
DI: digoxin, warfarin, clarithromycin,
erythromycin, gemfibrozil, grapefruit juice,
verapamil
Adverse Effects
(common and
severe)
increased liver
function tests,
myopathy,
rhabdomyolysis
increased liver
function tests,
myopathy,
rhabdomyolysis
Initial dose;
typical dose
Monitoring
20mg; 2080mg one time a
day / at nights
international
normalized ratio
(INR)
10, 40mg; 1040mg one time a
day
LFTs, creatinine
kinase (CK)