A double-blind, placebo-controlled, multicenter trial was undertaken to assess the
antihypertensive efficacy and tolerability of a controlled-release (Coat-Core [CC]
tablet) formulation of the second-generation
dihydropyridine calcium channel antagonist,
nisoldipine. Of the 208 patients with mild-to-moderate
essential hypertension, two were excluded from the main efficacy analysis, and the rest randomized into one of four treatment groups, to receive either placebo, or
nisoldipine CC at doses of 10, 20, or 30 mg once daily for 6 weeks, following a 4-week placebo run-in period. Blood pressure measurements (supine, standing, diastolic, and systolic) were taken at trough plasma levels, 24 h after previous dosing at 2-week intervals throughout the study. Adverse events and laboratory parameters (plasma
lipid and
glucose levels, and thyroid function) were monitored. All three doses of
nisoldipine CC lowered blood pressure, as compared with placebo, 24 h after dosing. At endpoint (after 6 weeks) mean changes in supine blood pressure from baseline were (systolic/diastolic) 0.9/-2.3, -8.0/-5.5, -16.9/-9.0, and -15.0/-10.3 mm Hg for the groups assigned to placebo and
nisoldipine CC 10, 20, and 30 mg, respectively. The response rates were 35%, 47%, and 63% for
nisoldipine CC 10, 20, and 30 mg, respectively. Twenty-four-hour ambulatory blood pressure monitoring showed that
nisoldipine CC effectively controlled blood pressure throughout the dosing interval. No change in heart rate was seen for all three doses of
nisoldipine CC over the 24-h dosing interval.
Nisoldipine CC was at least as effective in black patients as in whites. Generally adverse events were not increased, except for peripheral
edema, with rates of 7% in placebo, and 6%, 9%, and 19%, respectively, in those receiving
nisoldipine CC 10, 20, or 30 mg daily. There were no clinically significant changes in blood
lipids,
blood glucose, or thyroid function. In conclusion, once-daily
nisoldipine CC at doses of 10 to 30 mg was an effective and well tolerated
antihypertensive agent, providing 24-h control of blood pressure without any increase in heart rate.