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 2003;362:782–88.
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
EUROPA: EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease - TRIAL DESIGN continued -
Age (years)
a
Female
History of coronary
artery disease
MI
Percutaneous coronary
intervention
Coronary bypass
surgery
Diabetes mellitus
BP (mmHg)
a
Systolic
Diastolic
Medications
Platelet inhibitors
Lipid-lowering
therapy
Beta-blockers
Calcium-channel
blockers
Baseline characteristics (%)
60
14.7
64.7
29.5
29.4
12.8
Placebo
(n=6108)
60
14.5
60.4
29.0
29.3
11.8
Perindopril
(n=6110)
a
Mean (SD)
137
82
92.7
57.3
61.3
31.0
Placebo
(n=6108)
137
82
91.9
57.8
62.0
31.7
Perindopril
(n=6110)
The EUROPA Investigators.
Lancet
2003;
362
:782–8.
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%, P<0.0003)
Primary endpoint reduced with perindopril in all predefined baseline subgroups (though not significant in all groups), including patients taking lipid-lowering therapy or β-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)
EUROPA: EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease - RESULTS continued -
Years after randomization
Proportion
with first
event (%)
0
0
1
2
3
4
5
4
8
12
Time to first occurrence of primary endpoint
The EUROPA Investigators.
Lancet
2003;
362
:782–8.
EUROPA: EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease - RESULTS continued -
P
Primary endpoint:
cardiovascular death,
MI, or cardiac arrest
Cardiovascular death
Nonfatal MI
Total mortality, nonfatal MI,
unstable angina, cardiac arrest
Total mortality
(9 to 29)
(
–
3 to 28)
(10 to 33)
(6 to 21)
(–
2 to 23)
20
14
22
14
11
0.0003
0.107
0.001
0.0009
0.1
Primary and selected secondary outcomes
488
215
295
904
375
No.
(8.0)
(3.5)
(4.8)
(14.8)
(6.1)
(%)
Perindopril
(n=6110)
603
249
378
1043
420
No.
(9.9)
(4.1)
(6.2)
(17.1)
(6.9)
(%)
Placebo
(n=6108)
Relative risk
reduction, %
(95% CI)
The EUROPA Investigators.
Lancet
2003;
362
:782–8.
EUROPA: EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease - RESULTS continued -
Previous MI
No previous MI
Hypertension
No hypertension
Diabetes mellitus
No diabetes mellitus
Lipid-lowering drug
No lipid-lowering drug
Beta-blockers
No beta-blockers
7910
4299
3312
8906
1502
10,716
6831
5387
7650
4568
n
11.3
7.3
12.0
9.1
15.5
9.0
8.3
11.9
10.2
9.4
8.9
6.4
9.8
7.3
12.6
7.4
7.0
9.3
7.6
8.7
Placebo
Perindopril
Primary events (%)
Perindopril better
Placebo better
Primary endpoint in predefined subgroups
The EUROPA Investigators.
Lancet
2003;
362
:782–8.
Dashed line indicates overall risk
1.0
2.0
0.5
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