Objective
To determine the long-term effects (four years) of perindopril
on the diabetic patients enrolled in EUROPA (12% of the study
population) in terms of the primary and secondary
endpoints.
Rationale
Cardiovascular disease accounts for 75% of all deaths among people
with diabetes of European origin. In the USA, coronary heart disease is present
in between 8% and 20% of people with diabetes over 45 years of age. Their
risk of heart disease is 2-4 times higher than in people who do not have
diabetes. It is the main cause of disability and death of people with type
2 diabetes in industrialised countries.
Angiotensin-converting enzyme inhibitors
(ACEIs) such as perindopril are known to be effective in treating
hypertensive patients with diabetes, particularly in terms of reducing the
incidence of
diabetic nephropathy and proteinuria in patients with microalbuminuria.
But
to date the effects of an ACEI on diabetic patients with coronary artery
disease, who are not necessarily hypertensive, have not been fully established.
Scientific Committee
Prof K Fox (Chairman, UK), Prof P J Grant (UK), Prof P Hildebrandt (Denmark), Prof C Kluft (Netherlands), Prof C E Mogensen (Denmark), Prof L Ryden (Sweden)
Study endpoints
Primary endpoint
 Combined risk
of cardiovascular death, MI (heart attack) and cardiac arrest (a sudden cessation
of heartbeat resulting in the loss of circulation) with successful resuscitation
(recovery).
Secondary endpoints
Risk of:
Cardiovascular mortality
Myocardial infarction (fatal and non-fatal)
Heart failure
Total mortality
Revascularisation procedures (PTCA or CABG)
Stroke
Unstable angina pectoris
Study design
As eligible patients were enrolled into the main EUROPA study, those with diabetes were identified. Of the 12,218 patients enrolled, 1,502 (12% of the patient population) were identified as diabetics.
After a 4-week run-in period, patients were randomly assigned to receive treatment
with either perindopril 8 mg once daily or placebo for four years on top of other
preventive therapies (aspirin, beta-blockers, statins). 721 of the identified
diabetic patients were allocated to the perindopril group, and 781 to the placebo
group.
Patients were seen at two and four weeks during the run-in period, then examined at three, six and 12 months and thereafter at six-monthly intervals. The last examinations were carried out in April 2003, at which time the average duration of treatment was four years.
Study patients
12,218 patients aged 26 to 89 years (mean age 60 years) without heart failure
were recruited and randomised if they had documented coronary artery disease,
which was defined as either:
Previous MI (heart
attack) at least three months before selection (65%)
Surgery or revascularisation
(55%).
Patient characteristics
The diabetic patients
were similar to the rest of the EUROPA study population in terms of baseline
characteristics; in addition previous myocardial infarction: 66%, previous revascularisation:
55% were similar.
Use of existing medications (platelet inhibitors: 93%, beta blockers: 64%, lipid
lowering agents: 53%, calcium channel blockers: 38%, nitrates: 52% and diuretics:
14%) were also at similar levels to those of the EUROPA population. There were
more patients with hypertension (40% vs. 27%) and peripheral vascular disease
(13% vs. 7%) in PERSUADE compared to EUROPA .
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