Interventional Cardiology and Angiology

The influence of Treatment with the AT1-Receptor-Antagonist Candesartan cilexetil (Atacand) on the Progression of Atherosclerosis in Patients with Renovascular Disease and Coronary Artery Disease. - Prevention of Atherosclerosis In Coronary Arteries (PAIC)

• The Incidence of Renal Artery Stenosis in patients with Coronary Artery Disease (CAD) is about 30 %. An increase in activity of renin-angiotensin-system with high levels of angiotensin II is the main factor causing renovascular hypertension. Angiotensin II-induced arterial hypertension - in contrast to other forms of hypertension - shows an increase in production of vascular 02-radicals and decrease in relaxation properties of vessels.
• The negative effects of angiotensin II (e.g. left-ventricular hypertrophy and arterial hypertension) are mainly mediated by the AT1-receptors and can be blocked by AT1-receptor-antagonists (4).
• Recent results suggest that patients with renovascular disease show more severe progression of coronary and peripheral atherosclerosis ; these effects are already evident in patients with plaques or only mild renal artery stenosis. (Gross C. M., Krämer J., , et al. Am J Cardiol 1997, 80, 1478-1481)
• Hypothesis:
• Even low grade renal artery stenoses contribute to an increase in circulating angiotensin II concentration. Increased plasma angiotensin II concentration is vasculotoxic by production of O2-radicals (3). AT1 receptor-antagonists can directly and idependently of their haemodynamic effects block these detrimental effects. The progression of atherosclerotic lesions can thereby be slowed or even halted.
• Objectives:
• The effect of the AT1-receptor-antagonist candesartan cilexetil on the progression of atherosclerosis, which is assumed to be independent of any haemodynamic effect will be studied.
• Primary objective
• To compare the effect of a 12 months treatment with either 8-16 mg candesartan cilexetil or placebo on the progression of coronary atherosclerosis in patients with mild renal artery stenosis, coronary artery disease and nomalized blood pressure.
• Primary efficacy variable: Change in mean coronary artery segment diameter after 6 and 12 month treatment as measured by quantitative coronary angiography.