EUROPA substudies, confirmation of pathophysiological concepts. European trial on reduction of cardiac events with perindopril in stable coronary artery disease.

In patients with coronary disease, ACE inhibitors may improve endothelial function in the coronary arteries as well as peripheral arteries, and may have anti-proliferative effects which might result in retardation of progression of coronary artery disease. In order to verify these pathophysiological concepts, a series of substudies will be conducted as part of the EUROPA programme. Angiographic and intravascular ultrasound examination of coronary arteries will be performed in approximately 400 patients before and after 3 years' treatment with either perindopril or placebo, in order to assess progression and possible regression of coronary lesions. B-mode ultrasonography of the brachial artery will be used as a model for changes in the coronary arteries, to assess endothelial function in response to ischaemia (reactive hyperaemia) and to vasoconstriction (cold pressor test). Three hundred patients will be investigated before and at different intervals after initiation of study treatment. In addition genetic characterization will be performed of patients participating in EUROPA in order to assess whether specific genotypes do respond more or less favourably to perindopril. In addition, the effect of perindopril will be investigated in patients with diabetes type II, since ACE inhibition in such patients may improve microvascular function and renal function. Integration of these substudies, as well as detailed analysis of other specific subgroups in EUROPA, will help us understand the effects of treatment with perindopril in patients with stable coronary artery disease.