MULTICENTER, DOUBLE-BLIND CLINICAL-TRIAL WITH DIFFERENT DOSES OF PINACIDIL IN PATIENTS WITH MILD-TO-MODERATE ESSENTIAL-HYPERTENSION

The antihypertensive efficacy and therapeutic safety of pinacidil, 12. 5 or 25 mg twice daily (BID), were assessed in a multicenter, double-b lind, crossover trial. Seventy-seven patients (mean age, 47.3 years) w ith mild-to-moderate essential hypertension were enrolled in the study and randomly assigned to one of the following schedules: sequence A: pinacidil 12.5 mg BID for 3 weeks; 1-week washout period (two placebo capsules per day); pinacidil 25 mg BID for 3 weeks. Sequence B: pinaci dil 25 mg BID for 3 weeks; 1-week washout (two placebo capsules per da y); pinacidil 12.5 mg BID for 3 weeks. Both drug doses (25 or 50 mg/d) were equally effective, producing a similar and significant reduction in systolic and diastolic blood pressures in the sitting and standing positions, Systolic blood pressure was reduced by approximately 7% to 8% from baseline in both sequences A and B. Diastolic blood pressure, measured in both positions, was reduced by 8% to 9% from baseline, He art rate did not appear to be influenced by either dose. Analysis of v ariance showed no significant differences between the sequences; the o nly highly significant difference was between the times (P < 0.0001). Of the patients given 12.5 mg BID in the first 3 weeks (sequence A), 1 0.8% reported adverse reactions, as did 7.7% of those given this dose second (sequence B). However, 25.6% of the patients given 25 mg BID fo r the first 3 weeks (sequence B) reported adverse reactions, compared with 9.1% given that dose in the last 3 weeks (sequence A), Although t he higher dose lowered blood pressure sooner, more adverse reactions o ccurred, The percentages of patients whose diastolic blood pressure re turned to normal were similar with both doses: 62.5% with 12.5 mg BID and 69.6% with 25 mg BID.