New England Journal of Medicine.
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Transcript New England Journal of Medicine.
Scott Morgan MSIII
November 2012
AstraZeneca Pharmaceuticals
Designed by Cleveland Clinic Coordinating
Center For Clinical Research
Previous studies
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
Lack of randomized clinical trials showing efficacy for
rosuvastatin vs atorvastatin in CAD modification leading
to changes in clinical outcomes
Tested the 2 most potent statins for slowed progression or
reversal of atherosclerosis in coronary arteries
Statins
Inhibit hydroxymethylglutaryl
(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%
Most effective statins for lowering LDL
Atorvastatin
Yield average decrease in LDL approaching 50%
Rosuvastatin
Yield average decrease in LDL exceeding 50%
Greater increase in HDL than atorvastatin
Randomized double-blind
Treatment with atorvastatin 80 mg daily or
rosuvastatin 40 mg daily
Serial intravascular ultrasonography of
coronary arteries
Baseline at beginning of study
After 104 weeks of treatment
1039 patients 18-75 years old
At least one vessel with 20% stenosis and a target vessel
for imaging with <50% stenosis
Not treated with statins in preceding 4 weeks – LDL >100
mg/dL
If treated – LDL > 80 mg/dL
Exclusions:
intensive lipid-lowering therapy >3 months in last year
Uncontrolled HTN
Heart failure
Renal dysfunction
Liver disease
When all patients in a study are included in
the final results even when they are lost to
follow up
Prevents non-randomized loss of participants
Without this number there can be artifact
that makes a variable appear more/less
effective
Using this study as a hypothetical example
If 50 from the rosuvastatin that would have had a large LDL
decrease drop out
35 had decreased LDL levels during the trial
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
Missing data
Lack of adherence to methods used for
experiment
In example:
What is 25 of the 35 would have seen an increase
in LDL levels if they had stayed in?
Rosuvastatin and atorvastatin caused a
significant decrease in atherosclerotic plaque
size
Significant difference in regression of total
atherosclerotic volume between medications
Difference between percent atheroma
volume was not significant
Patients can have a decrease in coronary
atherosclerosis when using rosuvastatin or
atorvastatin
Reduction in atherosclerotic plaques is not
significant enough to justify one over the
other
Larger decrease in LDL and increase in HDL
with rosuvastatin during study
Did not use ITT
Thought the groups were still randomized and unaffected
Not ethically possible to measure disease progression in placebotreated patients
Did not look at asymptomatic patients
Did not look at alternative methods vs statins
Some newer methods of evaluating atherosclerotic plaques might
be more accurate
Funded by pharmaceutical company
Rating: IIa
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