IDEAL Trial

Incremental Decrease in Clinical Endpoints Through

Aggressive Lipid Lowering (IDEAL) Trial

Presented at
The American Heart Association
Scientific Session 2005
Presented by Dr. Terje Pedersen
 IDEAL Trial: Background

Several recent studies have evaluated a regimen of high-dose statin compared with
a lower-dose, usual care statin regimen in the setting of stable or unstable acute
coronary syndromes, including TNT, PROVE-IT TIMI-22 and A to Z.
In the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI-
22) study of patients recently hospitalized with acute coronary syndromes, aggressive
lipid lowering with 80 mg per day of atorvastatin provided more protection from death
and cardiovascular events than 40 mg per day of pravastatin.
The Treating to New Targets (TNT) study demonstrated that aggressive lipid
lowering with 80 mg per day of atorvastatin provided greater protection from major
cardiovascular events than low-dose atorvastatin in stable CHD patients.
On the other hand, the Aggrastat to Zocor (A to Z) trial showed that treatment with
high-dose simvastatin failed to show a significant reduction in the primary composite
endpoint of cardiovascular death, MI readmission for ACS or stroke.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Study Design
8,888
8,888 patients 80 years with
with definite
definite history
history of
of myocardial
myocardial infarction
infarction and qualified for
stain
stain therapy
therapy at
at time
time of
of recruitment
recruitment
Pts.
Pts. on
on statin
statin therapy
therapy at
at baseline:
baseline: simvastatin
simvastatin (50%),
(50%), atorvastatin
atorvastatin (11%),
(11%), pravastatin
pravastatin (10%);
(10%); baseline
baseline LDL
LDL 121.5
121.5 mg/dL;
mg/dL;
total
total cholesterol
cholesterol 196
196 mg/dL;
mg/dL; median
median time
time from
from last
last MI
MI 21
21 mos
mos in
in atorvastatin
atorvastatin group,
group, 22
22 mos
mos in
in simvastatin
simvastatin group
group
19%
19% female,
female, mean
mean age
age 62
62 yrs,
yrs, fasting
fasting blood
blood samples
samples were
were obtained
obtained at
at baseline,
baseline, 12
12 weeks,
weeks, 24
24 weeks,
weeks, 11 year
year and
and each
each
year
year thereafter,
thereafter, mean
mean follow-up
follow-up median
median of
of 4.8
4.8 years
years
Randomized
Randomized

High-dose
High-dose atorvastatin
atorvastatin Standard-dose
Standard-dose simvastatin
80
80 mg/day
mg/day 20
20 mg/day
mg/day
IfIf LDL
LDL was
was <40
<40 mg/dL
mg/dL at
at 24
24 wks
wks IfIf cholesterol
cholesterol >190
>190 mg/dL
mg/dL at
at 24
24 wks
wks
dose
dose could
could be
be reduced
reduced to
to 40
40 mg/day
mg/day dose
dose could
could be
be increased
increased to
to 40
40 mg/day
mg/day
n=4,439
n=4,439 n=4,449
n=4,449

Primary Endpoint:
Endpoint: Composite
Composite of
of major
major coronary
coronary event,
event, defined
defined as
as coronary
coronary death,
death,
hospitalization
hospitalization for
for non-fatal
non-fatal acute
acute MI
MI or
or resuscitated
resuscitated cardiac
cardiac arrest.
arrest.
Secondary Endpoint: Major Major cardiovascular
cardiovascular events,
events, anyCHD
anyCHD event,
event, hospitalization
hospitalization with
with aa
primary
primary diagnosis
diagnosis of
of congestive
congestive heart
heart failure,
failure, peripheral
peripheral artery
artery disease,
disease, any
any cardiovascular
cardiovascular events
events
and
and all-cause
all-cause mortality.
mortality.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Primary Endpoint
Primary Composite of major coronary event * (%)
p = 0.07

The primary composite

endpoint of major
coronary event occurred
in 9.3% of the
atorvastatin group and
%

10.4% of the simvastatin

group.

* Major coronary event defined as coronary

death, hospitalization for non-fatal acute MI
or resuscitated cardiac arrest.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Primary Endpoint cont.
Among the components of the primary endpoint, there was no difference
in CHD death or cardiac arrest with resuscitation, but nonfatal MI occurred
less frequently in the atorvastatin group.
p=0.02

p=0.90
%

p=NS

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Secondary Endpoints
Major cardiovascular events and any
cardiovascular event (%) Major cardiovascular
events, defined as any
p<0.001 primary event plus
stroke, occurred less
often in the atorvastatin
group.
p=0.02
Any cardiovascular
%

event, defined as major

CV event plus
hospitalization for CHF
and peripheral artery
disease, also occurred
less often in the
atorvastatin group.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Serious Adverse Events
Serious adverse events and adverse event resulting
in permanent study drug discontinuation (%)
p=0.42 There was no difference in
the frequency of serious
adverse events, but adverse
event resulting in
permanent drug
discontinuation was more
frequent in the atorvastatin
group.
%

p<0.001
Liver enzyme elevation
occurred more frequently in
the atorvastatin group as
did myalgia.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Serious Adverse Events cont.
Liver enzyme elevation and myalgia (%)

p<0.001

Liver enzyme
p<0.001 elevation
ALT >3x upper occurred more
limit of normal frequently in the
atorvastatin
%

group as did
myalgia.

www. Clinical trial results.org Presented at AHA 2005

 IDEAL Trial: Summary

Among patients with a previous myocardial infarction, treatment with

high-dose atorvastatin was associated with a directional but non-
significant reduction in the primary composite endpoint of major
coronary events compared with standard dose simvastatin at five year
follow-up.
The present trial further extends the evaluation of aggressive lipid-
lowering to the setting of post-myocardial infarction patients.
While there was a reduction in the secondary endpoint of recurrent
MI, adverse events and liver enzyme elevations were more frequent in
the high-dose atorvastatin group, highlighting the need for careful
monitoring of patients on this regimen.

www. Clinical trial results.org Presented at AHA 2005