Transcript PERSUADE - EUROPA Trial

The diabetic sub study of
K Fox, W Remme, C Daly, M Bertrand, R Ferrari, M Simoons
On behalf of the EUROPA investigators.
Background

ACE inhibitor therapy of proven benefit in
secondary prevention in myocardial infarction
and heart failure

EUROPA concluded that perindopril was also
beneficial in patients with CAD, without heart
failure and with broad range of risk

Within the coronary disease population,
diabetics are a subpopulation at high risk
Aim of the study
To investigate the effect of the ACE inhibitor
perindopril 8 mg once daily
added to standard therapy
on cardiovascular events
in diabetic patients
with documented coronary disease
Study endpoints
Primary endpoint

CV mortality + non fatal MI + cardiac arrest
Secondary endpoints

Fatal and non-fatal MI

Non-fatal MI

Stroke

Hospitalisation for heart failure

Development of renal failure
Patient population

Known diabetes at randomisation: n=1502

Male or female > 18 years of age

Documented coronary disease

Not scheduled for revascularisation

No clinical signs of heart failure
Baseline characteristics
EUROPA
PERSUADE n=1502
Perindopril
Placebo
(mean ± SD)
(mean ± SD)
(mean ± SD)
Age (yrs)
60 ± 9
62 ± 9
62 ± 9
Male (%)
85
83
81
Weight (kg)
81 ± 12
83 ± 13
82 ± 13
SBP (mmHg)
137 ± 15
140 ± 15
140 ± 16
DBP (mmHg)
82 ± 8
81 ± 8
82 ± 8
Medical history & risks
EUROPA
PERSUADE n=1502
Perindopril
Placebo
(%)
(%)
(%)
MI
65
65
68
CABG
32
30
33
PCI
29
27
26
Stroke / TIA
3
6
5
PVD
7
14
12
Hypertension
27
38
41
Hyperlipidemia
63
61
61
Clinical outcome
(%)
16
14.1
PERSUADE
14
11.1
12
10
EUROPA
8.9
8
8.9
6.5
7.1
6.0
6
3.8
4
2.7
2.5
1.6
2
1.3
1.0 0.6
0
Primary
Endpoint
Total
Mortality
CV
Mortality
MI
Stroke
Heart
Failure
Doubl.
Creatinine
RRR with perindopril
Perindopril
better
Placebo
better
Primary Endpoint
Total Mortality
CV mortality
All MI
Non Q MI
Heart Failure
Stroke
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8 (%) RRR
Primary endpoint
% CV death, MI and cardiac arrest
20
PERSUADE
RRR 19%
placebo
perindopril
p=0.131
16
placebo
12
PERSUADE
perindopril
8
EUROPA
4
0
0
1
2
3
Years from randomisation
4
5
Fatal and non fatal MI
(%)
14
PERSUADE
RRR 23%
p=0.143
placebo
10
6
placebo
perindopril
perindopril
PERSUADE
4
EUROPA
0
0
1
2
3
Years from randomisation
4
5
Heart Failure
(%)
4
PERSUADE
RRR 46%
placebo
p=0.06
2
perindopril
placebo
PERSUADE
perindopril
EUROPA
0
0
1
2
3
Years from randomisation
4
5
Summary of results

In PERSUADE, the relative risk reduction with
perindopril on 1° and 2° endpoints was similar to
that in the main EUROPA population

Primary endpoint

Fatal and nonfatal MI RRR 23%

Heart Failure
RRR 19%
RRR 46%
Conclusion
Perindopril 8 mg once daily reduces
cardiovascular events
in patients with coronary disease
and diabetes
NNT to prevent one cardiovascular death
or nonfatal myocardial infarction is just
27 patients over 4 years