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.
Gremmler
B
B
Department of Cardiology, Marienhospital, Josef-Albers-Strasse 70, D 46236, Bottrop, Germany.
Kunert
M
M
Schleiting
H
H
Ulbricht
L J
LJ
D000179:Acrylates / Q000627:therapeutic use*; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013876:Thiophenes; D016277:Ventricular Function, Left / Q000187:drug effects*
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan