PRAZOSIN IN HYPERTENSION: CLINICAL STUDIES WITH SPECIAL REFERENCE TO INITIATION OF THERAPY

This paper reports experiene with the initiation of therapy with prazosin and the findings of an open evaluation of 100 hypertensive patients treated with this drug. Twenty‐four patients with hypertension, with a mean age of 50 years, were given 1 mg of prazosin orally. Blood pressure was assessed at 15‐minute intervals, with the patients recumbent and erect, for up to 270 minutes. Fourteen had symptoms of postural hypotension—four mild, seven moderate and three severe. The mean maximum erect blood pressure reduction in the symptomatic group was 67/52 mm Hg at a mean of 90 minutes from the time of the dose. Subsequent therapeutic response was better in those patients experiencing an abrupt initial response. Twenty‐two further patients were given a single dose of 0·5 mg (tablet); of those 11 were included in a double‐blind within‐patient crossover study with placebo, in the same manner as the 1 mg trial. There were no postural symptoms or significant tachycardia with the initial 0·5 mg dose, and the mean maximum erect diastolic blood pressure reduction was 25 mm Hg. Placebo produced a mean erect blood pressure reduction of 27/11 mm Hg, and prazosin produced a reduction of 39/27 mm Hg. The mean prazosin‐placebo blood pressure difference was 12/16 mm Hg( P < 0·05). These data indicate that most patients experience some postural hypotension after the first dose of prazosin, that symptoms occur only when the fall is marked, and that the extent of the fall is dose related. At the Napier Hypertension Clinic, therapy is now initiated with 0·5 mg of prazosin given twice daily for three days and thrice daily for a further three days, followed by 1 mg three times daily for a further three days and a slow increase to 2 mg three times daily. If hypertension is still uncontrolled, either a beta‐adrenoreceptor blocking agent or a thiazide diuretic is added and the amount increased to maximum therapeutic doses. If blood pressure is still uncontrolled, the dose of prazosin is then increased progressively to 20 mg/day. A small initial dose with gradual increments has markedly reduced the incidence of initial side effects. Clinical experience with 100 patients has confirmed the efficacy of prazosin used alone or in combination with other antihypertensive agents. When prazosin was added to the existing antihypertensive regimen of 50 patients whose blood pressure was poorly controlled, 72% became normotensive. Treatment was initiated with prazosin in a further 50 patients. Satisfactory control was achieved with prazosin alone in 24, and 20 became normotensive. The remaining 26 received in addition a beta‐adrenoreceptor blocking agent (together with a thiazide diuretic in 14 cases). While prazosin alone produced a mean blood pressure fall of 21/13 mm Hg in this group, the combined therapy achieved a further blood pressure fall of 21/15 mm Hg, and 73% became normotensive.