DOSE-RESPONSE EVALUATION OF ONCE-DAILY THERAPY WITH A NEW FORMULATIONOF DILTIAZEM FOR STABLE ANGINA-PECTORIS

Diltiazem hydrochloride in a once-daily capsule formulation (DCD) has recently been approved in the United States for the treatment of mild to moderate hypertension and chronic stable angina pectoris. This tria l evaluated the dose response of DCD in patients with chronic stable a ngina pectoris. In a multicenter, randomized, double-blind, parallel-d esign trial, the effects and tolerability of once-daily therapy with p lacebo or DCD (60, 120, 240, 360, or 480 mg) were evaluated 24 hours a fter dosing, following 3 weeks of therapy in 227 patients with reprodu cible stable exertional angina pectoris. A significant linear dose tre nd (p = 0.004) was present across the 6 treatment groups far the prima ry end point-time to exercise termination at 24 hours after dosing-usi ng a standard Bruce treadmill excercise test. A significant linear dos e trend was also seen for timi to 1 mm ST-segment depression at 24 hou rs after dosing. Similar effects on exercise parameters were also seen at 4 hours after dosing. A linear dose trend (p = 0.04) was noted rel ative to the overall anginal attacks during daily activities and for a nginal attacks during exercise (p = 0.02). Overall frequency of treatm ent-related adverse effects was dose-related and occurred in 24.4% and 17.5% of patients treated with DCD and placebo, respectively. At a do se up to 240 mg/day, improvement in exercise tolerance was achieved wi thout an associated increase in the rate of treatment-related adverse events compared with placebo. The results of the study suggest that 12 0 mg of DCD would be the starting dose, with careful titration up to 3 60 mg/day in individual patients for maximal therapeutic efficacy.