Verapamil and trandolapril alone and in fixed combination in moderate essential hypertension: a multicenter, double-masked study

Abstract

We compared the efficacy of fixed combination therapy with verapamil sustained release (SR)/trandolapril with that of each agent alone in a randomized, double-masked, parallel-group, multicenter study involving 310 patients (180 men and 130 women; mean age, 55.6 years) with moderate essential hypertension (defined as sitting diastolic blood pressure [DBP] ⩾ 100 and <110 mm Hg). After a 4-week placebo run-in period, patients were randomized to receive verapamil SR 180 mg (102 patients), trandolapril 2 mg (105 patients), and verapamil SR 180 mg/trandolapril 2 mg (103 patients) each once daily for 8 weeks. Combination therapy produced a significantly greater mean reduction in sitting DBP (13.2 mm Hg) than either verapamil SR (9.6 mm Hg) or trandolapril (10.9 mm Hg) alone. The estimated adjusted mean contribution to the DBP-reducing effect of combination therapy was 2.3 mm Hg for verapamil SR and 3.6 mm Hg for trandolapril. Overall, combination therapy was significantly superior to monotherapy with either agent. At the last visit 50.5% of patients receiving combination therapy showed normalization of sitting DBP (<90 mm Hg) compared with 32.4% receiving verapamil SR and 41.9% receiving trandolapril; response rates (normalization of or reduction of DBP ⩾ 10 mm Hg) were 69.9% for patients receiving combination therapy, 49.0% for patients receiving verapamil SR, and 59.0% for patients receiving trandolapril. All three treatments were safe and well tolerated. The profile of adverse events with combination therapy was consistent with that known for each component drug. Fixed low-dose combination therapy with verapamil SR 180 mg/trandolapril 2 mg would be a suitable treatment option for patients with moderate essential hypertension, including those who have not responded to other forms of therapy.