Clinical, hemodynamic, and neuroendocrine effects of chronic prazosin therapy for congestive heart failure

We report our hemodynamic, clinical, and neuroendocrine observations during long-term (8 weeks) prazosin (PZN) administration to assess the efficacy of this agent in the long-term therapy of congestive heart failure (CHF) and to emphasize the potential role of neuroendocrine mechanisms in the determination of overall drug effect. During long-term PZN therapy there is improvement in functional status, exercise tolerance, and left and right ventricular ejection fractions. However, we also observed an increase in fluid retention and attenuation of the initial hemodynamic and clinical responses to the drug. Plasma renin activity and plasma norepinephrine concentration are increased during long-term PZN therapy despite clinical and hemodynamic improvement and potentially may be involved in the pathogenesis of the increased fluid retention and hemodynamic attenuation. Three pharmacologic considerations appear relevant to the use of an alpha-adrenergic antagonist such as PZN in CHF therapy: (1) the drug response may be related to the baseline level of sympathetic tone. (2) The dose-response pattern exhibits a plateau phase, beyond which higher doses cause little further effect. (3) The overall drug effect is the sum of its direct actions and the secondary actions of the neuroendocrine response it elicits.