Inflammation and Coronary Artery Disease: Role of AT1-Receptor Antagonism
Cardiovascular diseases, especially coronary artery disease, are the most common cause for death in industrialized nations. In coronary artery disease endothelial cell damage and an increased number of monocytes/macrophages and T lymphocytes infiltrating the arterial wall form atherosclerotic lesions. Furthermore, an enhanced migration and proliferation of vascular smooth muscle cells can be demonstrated in the early stages of atherosclerosis. In this process inflammatory events contribute to the progression of atherosclerotic lesions and to the development of unstable plaques. In atherogenesis and especially in unstable rupturing plaques the renin angiotensin system is of considerable significance. In atherosclerotic lesions ACE and AT1 receptor expression is upregulated influencing not only endothelial cells but also macrophages and lymphocytes. ACE inhibition and AT1 receptor antagonism are accompanied by a marked reduction of atherogenesis.
The aim of this trial is to assess the efficacy and tolerability of telmisartan (Micardis®, Germany) after one dose daily in patients with hypertension and coronary heart disease. This investigation is intended to test not only the effect on the blood pressure but also whether telmisartan has any effect on inflammatory parameters associated with coronary heart disease.
Drug: telmisartan 40 mg
Drug: placebo 40 mg
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Pilot Study: Inflammation and Coronary Artery Disease. Role of AT1 Receptor Antagonism|
- Alterations in the inflammatory parameters: hsCRP, IL-6, IL-10, sICAM-1, TNF-alpha, MCP-1, LFA, MAC-1, L- selectin, FcyRIII and PECAM-1
- Alterations of clinical parameters such as clinical outcome, and changes in blood pressure. Safety and tolerability in terms of incidence and severity of adverse events, changes in physical examination, heart rate, laboratory parameters, and 12-lead-ECG.
|Study Start Date:||December 2001|
|Estimated Study Completion Date:||May 2004|
Randomised, double-blind and placebo-controlled parallel group design
Planned/actual number of subjects:
Enrolled: 40/50 randomised: 40/42 completed: 40/42
Diagnosis and main criteria for inclusion:
Treated essential hypertension with a mean seated DBP/SBP smaller than 95 mmHg/160 mmHg, coronary artery disease confirmed by catheterization and age equal or greater than 18 years of age.
Duration of treatment:
12 weeks: telmisartan 40 mg or placebo 40 mg
The statistical null hypothesis is that in patients with CAD and mild-to-moderate hypertension, a 84-day therapy with 40 mg telmisartan causes changes in inflammatory and leukocyte adhesion parameters. The alternative hypothesis is that this therapy does not influence inflammatory and leukocyte adhesion parameters. This hypothesis is tested by the nonparametric Wilcoxon test for unpaired samples.
Placebo 40 mg
|Universitätsklinik des Saarlandes|
|Homburg/Saar, Germany, 66421|
|Study Chair:||Boehringer Ingelheim Study Coordinator||B.I. Pharma GmbH & Co. KG|