Transcript EUROPA

Clinical implications
Burden of coronary disease

56 millions deaths worldwide in 2001

29% due to CV disease (~ 16 millions)
(37% are foreseen in 2020)

20 millions of people in the EU have
coronary disease
Clinical expression of coronary disease
Unstable
angina
Stable
Angina
MI
Coronary
Disease
Silent
ischemia
Heart
failure
Sudden
death
Benefit of ACE inhibition
%
Perindopril
Placebo
9.9
8.0
6.8
6.1
5.2
3.5
6.9
4.1
0.1
CV death, MI CV death
Card. arrest
MI
0.2
Card.arrest
Death
Absolute benefits
Perindopril 8 mg once a day prevents one
cardiovascular death, non fatal MI or cardiac
arrest among every
50 patients with coronary disease treated for
4 years
For a country of 60 million inhabitants, this means that perindopril
over a 4 year period will stop 50 000 heart attacks or CV deaths
% Death, MI, Cardiac arrest
15.2
%
12.7
8.1
5.2
6.2
Low
6.2
Medium
High risk
Age, gender, previous MI, previous CABG/PCI,
PVD or stroke, hypertension, diabetes,
smoking, hyperchol., lipid lowering, -blockers.
Myocardial infarction
64% of patients had an history of MI
 20%
within 1 year of the MI
 47%
between 1 and 5 years after MI
 33%
more than 5 years after MI
Sub-groups analysis
Perindopril
better
Placebo
better
RRR (%)
Lipid lowering drug
16.3
No lipid lowering drug
22.3
-blockers
26.4
No -blockers
7.0
Calcium blockers
15.8
No calcium blockers
22.2
0.5
92% patients on platelet inhibitors
1.0
2.0
Interaction
A formal interaction analysis was performed for
the effect of perindopril in relation to:

-blockers

Lipid lowering drugs

Calcium antagonists
Interaction effect was not significant in all 3 analyses
The treatment effect of perindopril
was independent of the other drugs
HOPE vs. EUROPA
Study population
HOPE
EUROPA
Age (yrs)
66
60
Female gender (%)
27
15
Known CAD (%)
80
100
Previous MI (%)
53
65
PVD (%)
43
7
Stroke/TIA (%)
11
3
Diabetes (%)
38
12
Hypertension (%)
47
27
Hypercholesterolemia (%)
66
63
HOPE vs. EUROPA
Baseline
HOPE
EUROPA
Antiplatelet drugs*
76 %
92 %
-blockers
39 %
62 %
Lipid lowering drugs
29 %
58 %
More extensive treatment in EUROPA than in HOPE
* Mostly aspirin
HOPE vs. EUROPA
Placebo outcomes standardised for 4.5 yrs FU
HOPE
EUROPA
Total mortality
12.2%
7.4 %
CV mortality
8.1%
4.4%
Q wave MI
3.2%
2.1%
Major annual event rates : 50 to 80 % higher in HOPE
Benefits for all coronary artery disease
patients
SOLVD
SAVE
AIRE
TRACE SOLVD
(prev)
HOPE
EUROPA
ALL CAD PATIENTS
Summary of results
In EUROPA, the largest and longest trial of stable,
optimally treated CAD patients, perindopril 8 mg/d
significantly reduced:

CV mortality + non fatal MI + cardiac arrest: 20%

CV mortality and non fatal MI: 19%

Fatal + non fatal MI: 24%

Heart failure: 39%
Benefits of results

Benefits occurred on top of recommended
therapy (92% platelet inhibitors, 58% lipid
lowering drugs, 62% -blockers) and are
consistent across predefined sub-groups

Perindopril should be considered for chronic
therapy in all patients with coronary disease