Improvement of cardiac output in patients with severe heart failure by useof 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-i nhibition and angiotensin II AT1-receptor-antagonists differ, an additional positive effect concerning left ventricular function can be expected in co mbining 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 pr otocol. Hemodynamic measurements by impedance cardiography were performed a t baseline and after 8.85 +/- 1.5 days of study medication treatment. Resul ts: Additional treatment with eprosartan resulted in a higher cardiac outpu t 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 additio nal treatment with the AT1-receptor antagonist eprosartan, given to severe heart failure patients, who received digitalis, diuretics and ACE-inhibitor s, resulted in a beneficial effect by increasing cardiac output. This effec t may be due to eprosartan's additional property of blocking the autocrine interaction of locally and not ACE-generated angiotensin II with their resp ective vascular and myocardial AT1-receptors as well as the influence on pr ejunctional AT1-receptors located on sympathetic nerve terminals. (C) 2000 European Society of Cardiology. All rights reserved.