EUROPA SUBSTUDIES, CONFIRMATION OF PATHOPHYSIOLOGICAL CONCEPTS

In patients with coronary disease, ACE inhibitors may improve endothel ial function in the coronary arteries as well as peripheral arteries, and may have anti-proliferative effects which might result in retardat ion of progression of coronary artery disease. In order to verify thes e pathophysiological concepts, a series of substudies will be conducte d as part of the EUROPA programme. Angiographic and intravascular ultr asound examination of coronary arteries will be performed in approxima tely 400 patients before and after 3 years' treatment with either peri ndopril or placebo, in order to assess progression and possible regres sion of coronary lesions. B-mode ultrasonography of the brachial arter y will be used as a model for changes in the coronary arteries, to ass ess endothelial function in response to ischaemia (reactive hyperaemia ) and to vasoconstriction (cold presser test). Three hundred patients will be investigated before and at different intervals after initiatio n of study treatment. In addition genetic characterization will be per formed 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 patient s with diabetes type II, since ACE inhibition in such patients may imp rove microvascular function and renal function. Integration of these s ubstudies, as well as detailed analysis of other specific subgroups in EUROPA, will help us understand the effects of treatment with perindo pril in patients with stable coronary artery disease.