Ambulatory blood pressure profiles in patients treated with once-daily diltiazem extended-release or indapamide alone or in combination.

Abstract

This randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy and safety of single daily dose diltiazem extended-release (XR) and indapamide, given alone and combined, in 255 male and 170 female patients with mild to moderate hypertension. Blood pressure was assessed both manually in the office and by 24-hour ambulatory blood pressure monitoring (ABPM) techniques. Between-treatment efficacy comparisons were based on ABPM plots and changes from baseline in supine systolic (SuSBP) and diastolic (SuDBP) blood pressure after 6 weeks of double-blind treatment. Periodic 12-lead electrocardiograms (ECG), clinical laboratory tests, and physical examinations were used to assess safety. Both diltiazem XR 180, 240, and 360 mg and indapamide 2.5 mg monotherapy reduced ambulatory blood pressure to a greater extent than placebo. The ABPM data demonstrate that 2.5 mg indapamide produces an additional reduction in diastolic blood pressure when combined with fixed doses of diltiazem XR (120, 180, and 240 mg). The reduction was consistent over the entire 24-hour recording period for all combinations. Compared with monotherapy groups, higher therapeutic response rates (SuDBP < or = 90 mm Hg or Delta SuDBP > or = 10 mm Hg decrease from baseline) were also observed with combination therapy. Office blood pressure data qualitatively and quantitatively supported the observations made from the ABPM data. There were no unexpected adverse events or side-effect trends and no dose-response or clinically significant laboratory, ECG, or physical examination adverse effects. The combination therapy regimens were well tolerated with safety profiles comparable with those of the individual therapies.