EUROPA: EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery dis

1
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease

• Purpose
• To determine whether the ACE inhibitor
  perindopril reduces cardiovascular risk in
  patients with stable coronary heart disease and
  no apparent heart failure
• Reference
• The EUROPA Investigators. Efficacy of
  perindopril in reduction of cardiovascular events
  among patients with stable coronary artery
  disease randomised, double-blind,
  placebo-controlled, multicentre trial (the EUROPA
  study). Lancet 200336278288.

2
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled
• Patients
• 12,218 patients with previous MI, angiographic
  evidence of coronary artery disease, coronary
  revascularization or a positive stress test
  patients with heart failure excluded
• Follow up and primary endpoint
• Primary combined endpoint cardiovascular death,
  MI or cardiac arrest. Mean 4.2 years follow up
• Treatment REPLACE
• Placebo or perindopril 8 mg daily

3
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - TRIAL DESIGN continued -
Baseline characteristics ()
Placebo
Perindopril
Placebo
Perindopril
(n6108)
(n6110)
(n6108)
(n6110)
a
a
Age (years)
BP (mmHg)
60
60
Systolic
137
137
Female
14.7
14.5
Diastolic
82
82
History of coronary
Medications
artery disease
Platelet inhibitors
92.7
91.9
MI
64.7
60.4
Lipid-lowering
57.3
57.8
Percutaneous coronary
29.5
29.0
therapy
intervention
Coronary bypass
29.4
29.3
Beta-blockers
61.3
62.0
surgery
Calcium-channel
31.0
31.7
Diabetes mellitus
blockers
12.8
11.8
a
Mean (SD)
The EUROPA Investigators.
Lancet
2003
362
7828.
4
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - RESULTS -

• Composite primary endpoint of cardiovascular
  death, MI and resuscitated cardiac arrest
  significantly reduced in perindopril group
  compared with placebo (8.0 vs. 9.9, Plt0.0003)
• Primary endpoint reduced with perindopril in all
  predefined baseline subgroups (though not
  significant in all groups), including patients
  taking lipid-lowering therapy or ß-blockers
• Nonfatal MI and combined endpoint of total
  mortality, nonfatal MI, unstable angina or
  resuscitated cardiac arrest also significantly
  reduced, but no significant difference in cardiac
  arrest alone
• Drug well tolerated as defined by discontinuation
  rate only marginally higher with perindopril (81
  vs. 83 at 3 years)

5
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - RESULTS continued -
Time to first occurrence of primary endpoint
Proportion
with first
12
event ()
8
4
0
0
1
2
3
4
5
Years after randomization
The EUROPA Investigators.
Lancet
2003
362
7828.
6
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - RESULTS continued -
Primary and selected secondary outcomes
Relative risk
Perindopril
Placebo
reduction,
P
(n6110)
(n6108)
No.
()
No.
()
(95 CI)
Primary endpoint cardiovascular death, MI, or
cardiac arrest
(9 to 29)
20
0.0003
488
(8.0)
603
(9.9)
Cardiovascular death
(

3 to 28)
14
0.107
215
(3.5)
249
(4.1)
Nonfatal MI
(10 to 33)
22
0.001
295
(4.8)
378
(6.2)
Total mortality, nonfatal MI, unstable angina,
cardiac arrest
(6 to 21)
14
0.0009
904
(14.8)
1043
(17.1)
Total mortality
(
2 to 23)
11
0.1
375
(6.1)
420
(6.9)
The EUROPA Investigators.
Lancet
2003
362
7828.
7
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - RESULTS continued -
Primary endpoint in predefined subgroups
n
Primary events ()
Placebo
Perindopril
Perindopril better
Placebo better
Previous MI
7910
11.3
8.9
No previous MI
4299
7.3
6.4
Hypertension
3312
12.0
9.8
No hypertension
8906
9.1
7.3
Diabetes mellitus
1502
15.5
12.6
No diabetes mellitus
10,716
9.0
7.4
Lipid-lowering drug
6831
8.3
7.0
No lipid-lowering drug
5387
11.9
9.3
7650
10.2
7.6
Beta-blockers
No beta-blockers
4568
9.4
8.7
1.0
2.0
0.5
Dashed line indicates overall risk
The EUROPA Investigators.
Lancet
2003
362
7828.
8
EUROPA EURopean trial On reduction of cardiac
events with Perindopril in stable coronary Artery
disease - SUMMARY -

• In patients with stable coronary heart disease
  and no apparent heart failure, perindopril
  reduced
• Composite endpoints of cardiovascular death, MI
  or resuscitated cardiac arrest, and total
  mortality, nonfatal MI, unstable angina or
  resuscitated cardiac arrest
• Nonfatal MI
• Benefit was similar in predefined subgroups