Scott Morgan MSIII
November 2012
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AstraZeneca Pharmaceuticals
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Designed by Cleveland Clinic Coordinating
Center For Clinical Research
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Previous studies
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Repeatedly show favorable LDL effects from statins
Slow progression of CAD
Might even lead to CAD regression
Comparison of LDL lowering capabilities between rosuvastatin
and atorvastatin
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Lack of randomized clinical trials showing efficacy for
rosuvastatin vs atorvastatin in CAD modification leading
to changes in clinical outcomes
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Tested the 2 most potent statins for slowed progression or
reversal of atherosclerosis in coronary arteries
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Statins
 Inhibit hydroxymethylglutaryl
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(HMG) CoA reductase
Block rate-limiting step in
cholesterol synthesis
Major effect is from increased
hepatic LDL receptors
Average 20-40% decrease in
LDL
Can raise HDL by 10%
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Most effective statins for lowering LDL
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Atorvastatin
 Yield average decrease in LDL approaching 50%
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Rosuvastatin
 Yield average decrease in LDL exceeding 50%
 Greater increase in HDL than atorvastatin
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Randomized double-blind
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Treatment with atorvastatin 80 mg daily or
rosuvastatin 40 mg daily
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Serial intravascular ultrasonography of
coronary arteries
 Baseline at beginning of study
 After 104 weeks of treatment
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1039 patients 18-75 years old
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At least one vessel with 20% stenosis and a target vessel
for imaging with <50% stenosis
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Not treated with statins in preceding 4 weeks – LDL >100
mg/dL
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If treated – LDL > 80 mg/dL
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Exclusions:
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intensive lipid-lowering therapy >3 months in last year
Uncontrolled HTN
Heart failure
Renal dysfunction
Liver disease
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When all patients in a study are included in
the final results even when they are lost to
follow up
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Prevents non-randomized loss of participants
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Without this number there can be artifact
that makes a variable appear more/less
effective
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Using this study as a hypothetical example
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If 50 from the rosuvastatin that would have had a large LDL
decrease drop out
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35 had decreased LDL levels during the trial
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Results of the study will not show how efficacious rosuvastatin
therapy
 Sample size is smaller
 Smaller percentage of patients show results
▪ Reality: 250/520 = 48%
▪ With ITT: 235/520 = 45%
▪ Without ITT: 200/470 = 43%
 LDL decrease will appear smaller than reality
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Missing data
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Lack of adherence to methods used for
experiment
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In example:
 What is 25 of the 35 would have seen an increase
in LDL levels if they had stayed in?
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Rosuvastatin and atorvastatin caused a
significant decrease in atherosclerotic plaque
size
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Significant difference in regression of total
atherosclerotic volume between medications
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Difference between percent atheroma
volume was not significant
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Patients can have a decrease in coronary
atherosclerosis when using rosuvastatin or
atorvastatin
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Reduction in atherosclerotic plaques is not
significant enough to justify one over the
other
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Larger decrease in LDL and increase in HDL
with rosuvastatin during study
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Did not use ITT
 Thought the groups were still randomized and unaffected
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Not ethically possible to measure disease progression in placebotreated patients
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Did not look at asymptomatic patients
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Did not look at alternative methods vs statins
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Some newer methods of evaluating atherosclerotic plaques might
be more accurate
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Funded by pharmaceutical company
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Rating: IIa
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Nicholls, Stephen J. et al. Effect of Two Intensive Statin
Regimens on Progression of Coronary Disease. New England
Journal of Medicine. 2011; 365:2078-2087. Dec 1, 2011