Improvement of Cardiac Output in Patients with Severe Heart Failure by Use of ACE-Inhibitors Combined with the AT1-Antagonist Eprosartan

BACKGROUND: The efficacy of ACE-inhibitor therapy is well documented in the treatment of chronic heart failure. As pharmacological mechanisms of ACE-inhibition and angiotensin II AT1-receptor-antagonists differ, an additional positive effect concerning left ventricular function can be expected in combining both classes of drugs. METHODS: Twenty patients (64.9+/-8.5 years) with advanced chronic heart failure (NYHA class III) receiving long-term medication with digitalis, diuretics and ACE-inhibitors were randomized to either eprosartan (540+/-96 mg/day) or placebo, according to a blinded protocol. Hemodynamic measurements by impedance cardiography were performed at baseline and after 8.85+/-1. 5 days of study medication treatment. RESULTS: Additional treatment with eprosartan resulted in a higher cardiac output than in the control group (P<0.05). While in the active treatment group cardiac output increased significantly from baseline (2.27-3.24 l/min, P=0. 039), there was no change in the control group. CONCLUSIONS: The additional treatment with the AT1-receptor antagonist eprosartan, given to severe heart failure patients, who received digitalis, diuretics and ACE-inhibitors, resulted in a beneficial effect by increasing cardiac output. This effect may be due to eprosartan's additional property of blocking the autocrine interaction of locally and not ACE-generated angiotensin II with their respective vascular and myocardial AT1-receptors as well as the influence on prejunctional AT1-receptors located on sympathetic nerve terminals.