Therapeutic application of prazosin in chronic refractory congestive heart failure: Tolerance and “tachyphylaxis” in perspective

Abstract

The cardiocirculatory actions of the oral vasodilator prazosin were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise and symptoms in patients with advanced long-standing congestive heart failure. The administration of oral prazosin (2 to 7 mg) reduced forearm venous tone and forearm vascular resistance. Concomitantly, mean systemic arterial pressure and left ventricular filling pressure decreased, and the cardiac index increased. These effects of a single dose of prazosin on left ventricular function were rapid in onset, maximal at 1 hour and sustained for the entire 6-hour period of observation. After two weeks of outpatient therapy with 2 to 7 mg of prazosin four times daily, echographic end-diastolic dimension decreased, whereas the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of prazosin therapy, and there was an improvement in the New York Heart Association functional class from 3.7 to 2.2. Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous beds, which are effectively translated into the beneficial hemodynamic effects of augmenting cardiac output and relieving excessive left ventricular end-diastolic pressure. The delayed vasodilator tolerance that occurs in 30 percent of the patients is prevented by the prior use of aldosterone antagonists and is easily treated when present. Subacute hemodynamic suppression of beneficial prazosin vasodilator actions is transient and does not preclude successful sustained prazosin therapy of severe heart failure.