Long-term ambulatory therapy with prazosin versus placebo for chronic heart failure: relation between clinical response and left ventricular function at rest and during exercise

The effects of oral prazosin (PZ), 15 to 20 mg/day, on symptoms, exercise performance and left ventricular (LV) function were assessed in a 6-month, double-blind, placebo-controlled study of patients in New York Heart Association functional class III. Ejection fraction (EF) was measured at rest and during upright bicycle exercise by equilibrium radionuclide angiography; end-diastolic volume, stroke volume and cardiac output were derived from corresponding count measurements. Although there was no statistically significant difference between clinical responses in the prazosin and placebo groups, qualitative differences suggested a clinical response to prazosin. Of the 9 patients who received PZ, 5 improved to functional class II and 2 became asymptomatic; the 2 nonresponders deteriorated to functional class IV when PZ was stopped. Four of 9 patients who received placebo improved to functional class II and 2 deteriorated to class IV. Exercise time tended to increase in the prazosin group (from 541 ± 204 to 630 ±100 seconds at 6 months) and decrease in the placebo group (from 539 ± 141 to 435 ±148 seconds at 6 months), but neither change was significant. Prazosin effected a sustained decrease in mean blood pressure of approximately 10 mm Hg at rest, and a quantitatively similar but insignificant decrease during exercise. Radionuclide EF increased and LV end-diastolic counts decreased significantly at rest and during exercise in the prazosin group, but not in the placebo group. Because changes in EF and end-diastolic counts were similar, stroke counts and count output were unchanged. Thus, long-term oral PZ therapy caused sustained changes in blood pressure and LV function in most patients in functional class III, but these changes were not uniformly translated into clinical improvement or increased exercise tolerance. Prazosin does not appear to increase cardiac output during exercise in patients with heart failure.