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.