Effects of different AT1-receptor antagonists in the therapy of severe heart failure pretreated with ACE inhibitors.

Background: The efficacy of ACE-inhibitors and beta blockers is well documented in the therapy of heart failure. As pharmacological mechanisms of ATI-receptor-antagonists differ, an additional positive effect can be expected when combining these drugs.

Methods: Eighty patients (67.9 +/- 9.9 years) with severe chronic heart failure receiving long-term medication with diuretics, ACE-inhibitors and partially beta blockers (72.5%), were randomized after clinical recompensation to eprosartan (477.5 +/- 143.7 mg/d), telmisartan (65.9 +/- 17.7 mg), candesartan (11.9 +/- 4.0 mg) or no sartan, according to a prospective study. Haemodynamic measurements by impedance cardiography were performed (mean observation time 15.8 days).

Results: Additional sartan treatment resulted in an improvement of cardiac output from 2.32 +/- 0.69 to 3.12 +/- 1.24 l/min (P = 0.003) in the eprosartan group, from 2.24 +/- 0.59 to 2.76 +/- 0.91 l/min (P = 0.001) in the telmisartan group and from 2.76 +/- 0.84 to 3.11 +/- 0.94 l/min (P = 0.02) in the candesartan group. Furthermore, a significant decrease of the total peripheral resistance was measured under eprosartan (23%; P = 0.002), telmisartan (18%; P = 0.002) and candesartan treatment (11.5%; P = 0.049); in the subgroup of combined therapy with beta blockers, ACE-inhibitors and ATI-antagonists a significant increase in cardiac output was also observed. No change was observed in the control group without additional sartan treatment concerning cardiac output and resistance reduction.

Conclusions: The additional treatment with different ATI-receptor-antagonists resulted in an increase of the cardiac output and a decrease of the peripheral resistance. This beneficial effect may be due to the additional property of sartans to block the interaction of locally and not-ACE-generated angiotensin II with their vascular and myocardial ATI-receptors.