Marked early attenuation of hemodynamic effects of oral prazosin therapy in chronic congestive heart failure.

Prazosin, in a single oral dose has been shown to induce balanced reduction in left ventricular preload and arteriolar resistance and therefore has been advocated as a potential agent of choice for the long-term treatment of patients with heart failure. However, preliminary reports have questioned the persistence of these beneficial effects. The effects of the first and the fifth consecutive administration of oral prazosin at Its maximal dose (3 to 10 mg every 6 hours) were compared in 11 patients with chronic congestive heart failure. Oral administration of the first dose resulted in a significant reduction in systemic vascular resistance (from 2,062 ± 498 to 1,560 ± 639 dynes sec cm^?5, P < 0.05), mean pulmonary wedge pressure (from 23.5 ± 6.2 to 13.7 ± 6.2 mm Hg, P < 0.05) and mean systemic blood pressure (from 88.8 ± 10.4 to 79.8 ± 11.1, P < 0.05). The drug also produced a significant increase in cardiac index (from 1.96 ± 0.3 to 2.53 ± 0.6, liters/min per m², P < 0.05), stroke volume index (from 22.2 ± 4.5 to 28.8 ± 6.4 ml/m², P < 0.05) and stroke work index (from 19.4 ± 4.2 to 26 ± 7.1, g-m/m², P <0.05), whereas the heart rate did not change significantly (87.7 ± 17 versus 88.4 ± 16 beats/ min).In contrast to the significant favorable effect demonstrated initially with prazosin, no significant hemodynamic changes were noted after the administration of the fifth consecutive dose. A comparison between the values at the peak response elucidated a complete abolishment of the effect on left ventricular filling pressure (13.7 ± 6.2 versus 22.5 ± 4.2 mm Hg, P < 0.05) with a greatly attenuated effect of the drug on systemic vascular resistance (1,560 ± 639 versus 1,816 ± 544 dynes sec cm^?5, P < 0.05). These data suggest an early development of tolerance to the beneficial hemodynamic effects mediated by oral prazosin and raise doubt regarding the value of this agent in the ambulatory treatment of patients with chronic congestive heart failure.