CLINICAL-EXPERIENCE WITH A ONCE-DAILY, EXTENDED-RELEASE FORMULATION OF DILTIAZEM IN THE TREATMENT OF HYPERTENSION

Although calcium channel blockers were only recently approved for antihypertensive therapy, 10 years of data have demonstrated their beneficial effects. Among the available calcium channel blockers, diltiazem hydrochloride appears to have a highly favorable side-effect profile. A new, extended-release formulation of diltiazem has been developed for the treatment of essential hypertension. The safety and efficacy of various once-daily doses of this new formulation were assessed in two multicenter studies. The first study was a dose-ranging trial of 275 patients with mild-to-moderate hypertension. Patients were randomly assigned to once-daily diltiazem (120, 240, 360, or 480 mg) or placebo for a 4-week, double-blind treatment period. A patient subgroup underwent ambulatory blood pressure monitoring (ABPM) twice. Once-daily diltiazem (dose range, 240-480 mg) significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion. ABPM results demonstrated consistent decreases in systolic and diastolic blood pressure throughout the 24-hour dosing interval. Dosages greater-than-or-equal-to 240 mg/day provided trough drug blood levels within the therapeutic range (i.e., greater-than-or-equal-to 40 ng/mL). The second study was a forced-escalation trial of 115 patients with mild-to-moderate hypertension. Patients were randomized to treatment with either placebo or escalating dosages of diltiazem (180 mg/day for 2 weeks, 360 mg/day for 2 weeks, and then 540 mg/day for 2 weeks). Statistically significant (p <0.01) reductions in supine systolic and diastolic blood pressure were observed with the 360 mg/day and 540 mg/day dosages. Dose escalations resulted in incremental blood pressure reductions and an increase in the percentage of responders. There was a significant correlation between diltiazem peak and trough plasma concentrations and antihypertensive effects in both studies, supporting the 24-hour efficacy of this extended-release formulation. Diltiazem administered once daily was found to be safe and well tolerated by the patients in these studies; adverse events were generally mild, with an incidence similar to placebo. Results indicate that this new extended-release formulation of diltiazem, administered once daily in doses >120 mg, effectively lowers systolic and diastolic blood pressure in patients with mild-to-moderate essential hypertension.