Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension.

Abstract

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, combination therapy of verapamil SR 240 mg plus indapamide 2.5 mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg daily, those patients with diastolic blood pressures of <95 mm Hg were excluded from further study; 137 remaining patients with sitting diastolic blood pressure of 95--115 mm Hg, representing "incomplete" responders to verapamil SR 240 mg, were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. Efficacy was assessed after 16 weeks of double-blind therapy or at end point. All three treatments significantly reduced sitting diastolic and systolic blood pressure from baseline levels. Compared with Group I (verapamil SR 240 mg daily), there was a significant reduction (p < 0.05) in Group II combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction (p < 0.05) in Group II (verapamil SR 480 mg daily) of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Patients who had the least change in blood pressure (diastolic blood pressure decreases of <5 mm Hg) to lead-in verapamil SR 240 mg daily, prior to randomization, tended to have a greater response to combination therapy than to verapamil SR 480 mg. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving verapamil SR 480 mg daily (Group II). There was a significantly greater withdrawal from Group II than the other two treatment groups (8.5% from Group III and 4% from Group I). This trial demonstrated that adding indapamide 2.5 mg to the incomplete responders of verapamil SR 240 mg enhances efficacy and was well tolerated.