SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
Status:
Terminated
Trial end date:
2004-10-01
Target enrollment:
Participant gender:
Summary
The aim of this trial is to evaluate the efficacy and safety of telmisartan 80 mg
administered once daily in patients with documented coronary artery disease (CAD) and a
probably cardiovascular risk profile concerning the amelioration of structural alterations
and endothelial function.
The primary objective of this trial is to evaluate the efficacy in particular with regard to
the percentage change of atheroma volume in the femoral artery.The secondary objective is to
evaluate the change in the plaque size- assessed by intravascular ultrasound, the increase in
Flow Dependent Dilation provoked by intraarterial infusion of three increasing concentrations
of Acetylcholine, and the change in seated systolic blood pressure.
Endothelial dysfunction is a primary event in atherogenesis and all known cardiovascular risk
factors have been associated with endothelial dysfunction before atherosclerotic vascular
disease manifests itself clinically. Pivotal to endothelial dysfunction is a disturbance in
the function of endothelium-derived nitric oxide (NO). Recently, it could be shown that acute
and chronic angiotensin-1 receptor antagonism reversed endothelial dysfunction in
atherosclerosis. In experimental atherosclerosis, AT1 receptor blockade appears to have
protective effects. Respective potential mechanisms include the prevention of endothelial
injury, the augmentation of NO activity, the inhibition of lipid peroxidation and an
antiproliferative effect. These findings together with the most recent data that losartan
improves endothelial function and NO activity suggest that AT1 receptor antagonism may also
be antiatherogenic in patients with atherosclerosis. Angiotensin II influences smooth muscle
cell migration, hyperplasia, and hypertrophy. Angiotensin II also enhances production of
local superoxide anion, which will inactivate nitric oxide. Inhibition of these reactions by
the AT1-Blocker telmisartan may therefore interfere with atherosclerotic plaque formation.