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Background : Coronary Artery Disease
Home : Healthcare professionals : EUROPA Design & Organisation
EUROPA Design & Organisation


To assess the long-term effects (four years) of ACE-inhibitor therapy with perindopril on the reduction of cardiac events in patients with proven stable coronary artery disease with/without signs of ischaemia, but without heart failure, irrespective of age, cardiovascular risk profile or ventricular function.

Study design and randomisation

This is a double-blind, randomised, placebo-controlled, multicentre trial. Patient recruitment into the study began in October 1997 and the follow-up ended in April 2003. 12,218 patients were randomised.

The study comprised an initial run-in period of two weeks during which patients received perindopril 4 mg once daily in addition to their existing medication(s). This was followed by a second two-week period during which patients received perindopril 8 mg once daily in addition to existing medication(s) on condition that the previous 4 mg once daily dose of perindopril was well tolerated.

Patients aged 70 years or older started on a lower dose. They received perindopril 2 mg once daily in the first week, 4 mg once daily in the second week and 8 mg once daily for the following two weeks, if the drug was well tolerated.

The four-week run-in period was then followed by a double-blind treatment period during which time patients received either perindopril 8 mg once daily or placebo for at least four years.

Examinations - Follow up

Patients were seen at two and four weeks during the initial four-week run-in period before being randomly assigned to one of the two treatment groups.

Following randomisation, patients were examined at three, six and 12 months and thereafter at six-monthly intervals. Follow up ended 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 clinical evidence of heart failure were recruited and randomised if they had documented coronary artery disease, which was defined as either:

Previous myocardial infarction (MI) at least three months prior to the selection visit (65%)

Percutaneous or surgical coronary revascularisation at least six months before the selection visit (55%)

Angiographic evidence of at least 70% narrowing of at least one major coronary artery (61%).

Male patients (85% of the study population) with a history of chest pain (4%) were also recruited if they had either:

Positive exercise test

Regional wall motion abnormalities during stress echocardiography or nuclear imaging

Transient perfusion defects during nuclear imaging.

Patient demographics

The analysis of the baseline characteristics of patients recruited into the study showed that:

85% were male

65% had suffered a previous MI

61% had coronary artery stenosis (angiographic evidence of =70% narrowing of at least one major coronary artery) removed in media materials)

55% had undergone previous revascularisation

12% had diabetes

27% had hypertension

63% had hypercholesterolaemia or received treatment for hypercholesterolaemia.

Study treatments

Patients received either perindopril 8 mg/day or placebo in addition to their existing medication(s). Existing medications included:

Platelet inhibitors (93% of the patient population)

Beta-blockers (62%)

Lipid-lowering agents (58%)

Study endpoints

Primary endpoint

Cardiovascular death, MI and cardiac arrest with successful resuscitation.

Secondary endpoints

Total mortality

MI (fatal and non-fatal)

Unstable angina pectoris

Cardiac arrest.

Cardiovascular mortality

Heart failure

Total mortality

Revascularisation procedures (PTCA or CABG)



Various sub-studies have been incorporated into the EUROPA trial to assess the effects of perindopril in patients with diabetes, as well as to provide data on the exact mechanism(s) by which this drug may reduce morbidity and mortality in coronary artery disease:

PERSUADE (PERindopril SUbstudy in coronary Artery Disease and diabEtes): this sub-study is examining patients (almost 1500) taking part in EUROPA who also have diabetes (12% of the study population). In addition to the objectives of the main EUROPA trial, this study will also detect the progression of diabetic nephropathy in this patient population.

PERSPECTIVE (PERindopril’S Prospective Effect on Coronary aTherosclerosis by angiographical and IntraVascular ultrasound Evaluation): this sub-study is investigating the effects of perindopril (almost 400 patients) on the progression and regression of coronary atherosclerosis using qualitative coronary angiography (QCA) and intravascular ultrasound (IVUS).

PERFECT (PERindopril Function of the Endothelium in Coronary artery disease Trial): this sub-study is examining the effect of perindopril (almost 300 patients) on endothelial function by measuring forearm circulation and flow-mediated vasodilatation of the brachial artery in response to perindopril administration.

PERTINENT (PERindopril – Thrombosis, InflammatioN, Endothelial dysfunction and Neurohormonal activation Trial): this sub-study is designed to evaluate the predictive value of several plasma and serum markers associated with atherosclerosis and the effects of perindopril on their levels (almost 1300 patients).

PERGENE (PERindopril and GENEtic characterisation of coronary artery disease patients): this sub-study is looking at the genetic characterisation of all patients in the EUROPA study population.

These sub-studies will provide valuable scientific knowledge on the origin and development of coronary artery disease and, in particular, how perindopril may exert its beneficial actions in patients with the disease.

The announcement of these sub-studies will follow in the future.

Study results (Click here)

The results of the EUROPA study were announced at the European Society of Cardiology (ESC) meeting in Vienna, 31 August, 2003.

This website is intended for an international audience. Drug related information may refer to unlicensed products or uses which may not be approved in your own country and you should therefore consult your local prescribing information.
This site is published and updated by the EUROPA study investigators. Site last updated March 21st 2006
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