Transcript Rimonabant in Obesity - Clinical Trial Results

PEACE Trial
Prevention of Events with Angiotensin
Converting Enzyme Inhibition (PEACE) Trial
Presented at
The American Heart Association
Scientific Sessions 2004
Presented by Dr. M. Pheffer
PEACE Trial
8,290 patients with stable coronary artery disease without heart failure
MI, CABG, or PCI at least 3 mo prior to enrollment, normal LV wall motion w/ EF>40%
82% male, mean age 64 years
90% received Aspirin, 60% beta-blockers, 70% lipid-lowering therapy
ACE Inhibitor Trandolapril
4mg/day
At 1 year, Trandolapril or open-label
ACE inhibitor taken by 81.9%
At 3 years, 74.5%
Placebo
At 1 year, 1.5% of patients on Ace
inhibitor
At 3 years, 8.3%
 n=4,132
n=4,158
Primary Endpoint:

Composite of cardiac death, MI, or revascularization at a mean follow-up
of 4.8 years
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Presented at AHA 2004
PEACE Trial: Primary endpoint
Primary Composite of cardiovascular
death, nonfatal MI, and coronary
revascularization
p = 0.43
25
21.9
22.5
20
• The primary composite
endpoint of cardiovascular
death, MI, and revascularization
was equal between the
Trandolapril and Placebo
groups at a mean follow-up of
4.8 years
15
• The primary endpoint was also
equivalent in all analyzed
subgroups
10
5
0
Trandolapril
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Placebo
Presented at AHA 2004
PEACE Trial: Primary Endpoint
The individual components of the primary endpoint were also equivalent in the
Trandolapril and placebo groups
p=0.65
16
12.4
12.0
p=0.24
12
p=1.00
p=0.67
6.5
%
8
5.3
4
3.5
7.1
5.3
3.7
0
Cardio death
Nonfatal MI
Trandolapril
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CABG
PCI
Placebo
Presented at AHA 2004
PEACE Trial: All Death
All-Cause Death
p = 0.13
10
8.1
8
• A slight reduction in all-cause
death seen in the Trandolapril
arm was not statistically
significant
7.2
6
4
2
0
Trandolapril
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Placebo
Presented at AHA 2004
PEACE Trial
CHF as the primary cause of hospitalization or death and new-onset diabetes were
both significantly lower in the trandolapril group. Neither analysis was a primary or
secondary endpoint.
New onset diabetes
CHF as primary cause of
hospitalization or death
p = 0.01
11.5
12
p = 0.02
5
9.8
4
9
2.8
6
%
%
3
3.7
3
2
1
0
0
Trandolapril
Placebo
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Trandolapril
Placebo
Presented at AHA 2004
PEACE Trial: Safety
Side effects leading to discontinuation
• There was a significantly
higher incidence of side effects
leading to drug discontinuation
in the Trandolapril group.
p < 0.001
25
• The Trandolapril group also
had significant increases in
cough and syncope
20
15
14.4
10
6.5
5
0
Trandolapril
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Placebo
Presented at AHA 2004
PEACE Trial: Summary
• Among patients with stable coronary artery disease and no heart failure, there was no difference in
the primary composite endpoint of cardiovascular death, nonfatal MI, and coronary revascularization
with the ACE inhibitor trandolapril or placebo.
• All individual components of the primary endpoint were equivalent between the two groups.
• A retrospective analysis of new onset diabetes and CHF as the primary cause of hospitalization or
death was found both to be lower in the trandolapril group.
• Trandolapril was associated with a significantly higher incidence of side effects leading to drug
discontinuation. Additionally, cough and syncope were each significantly higher in the trandolapril
cohort.
• The lack of benefit from ACE inhibitor therapy seen in this trial differs from the results of several
previous trials including the HOPE and EUROPA trials, which showed significantly lower incidences
of cardiovascular death, MI, stroke, and cardiac arrest in patients treated with ACE inhibitors than in
those treated with placebo.
•A possible reason for the lack of benefit with trandolapril could be that most patients were more
aggressively managed for risk factors with lipid-lowering medication and previous revascularization.
In accordance with this hypothesis, the PEACE trial had a lower event rate than the EUROPA and
HOPE trials.
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