Effects of AT1 receptor antagonist therapy in patients with severe heart failure pretreated with angiotensin-converting enzyme inhibitors.

Background: The efficacy of angiotensin-converting enzyme (ACE) inhibitors is well documented in the treatment of chronic severe heart failure. Because pharmacological mechanisms of angiotensin II type 1 (AT1) receptor antagonists differ from the effects of ACE inhibitors, an additional positive effect can be expected by combining these drugs.

Methods: Sixty patients (mean age 68.3+/-10.0 years) with severe chronic heart failure receiving long term medication with digitalis, diuretics, ACE inhibitors and in part beta-blockers (68.3%) were randomly assigned after clinical recompensation to three groups: additional therapy with eprosartan (477.5+/-143.7 mg/day), telmisartan (65.9+/-17.7 mg/day) and control group according to a prospective study design. Hemodynamic measurements by impedance cardiography were performed before and during the observation period (9.6+/-3.4 days).

Results: Additional sartan treatment resulted in an improvement in cardiac output from 2.32+/-0.69 L/min to 3.12+/-1.24 L/min (P=0.003) in the eprosartan group and from 2.24+/-0.59 L/min to 2.76+/-0.91 L/min (P=0.001) in the telmisartan group; cardiac output in the control group did not increase. Furthermore, a significant decrease in total peripheral resistance was observed during treatment with eprosartan (23%, P=0.002) and telmisartan (18%, P=0.002). In the subgroup receiving combined therapy with beta-blockers, ACE inhibitors and AT1 antagonists, a significant increase in cardiac output was also observed.

Conclusions: The additional treatment with AT1 receptor antagonists resulted in an increase in the cardiac output and a decrease in the peripheral resistance. This beneficial effect may be due to the additional property of sartans to block the interaction of locally and non-ACE-generated angiotensin II with their respective vascular and myocardial AT1 receptors.