Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension

Abstract Background: Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. Objectives: Two studies were conducted to compare the efficacy of various combinations of amlodipine and valsartan administered once daily with their individual components and placebo in patients with mild to moderate essential hypertension (mean sitting diastolic blood pressure [ MSDBP ] ≥95 and Methods: The 2 studies were multinational, multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group trials. In study 1, patients were randomized to receive amlodipine 2.5 or 5 mg once daily, valsartan 40 to 320 mg once daily, the combination of amlodipine 2.5 or 5 mg with valsartan 40 to 320 mg once daily, or placebo. In study 2, patients were randomized to receive amlodipine 10 mg once daily, valsartan 160 or 320 mg once daily, the combination of amlodipine 10 mg with valsartan 160 or 320 mg once daily, or placebo. The primary efficacy variable in both studies was change from baseline in MSDBP at the end of the study. Secondary variables included the change in mean sitting systolic blood pressure (MSSBP), response rate (the proportion of patients achieving an MSDBP Results: A total of 1911 patients were randomized to treatment in study 1 (1022 amlodipine + valsartan; 507 valsartan; 254 amlodipine; 128 placebo); 1250 were randomized to treatment in study 2 (419, 415, 207, and 209, respectively). In all treatment groups in both studies, the majority of patients were white (79.5% study 1, 79.4% study 2) and male (53.5% and 50.3%, respectively). The overall mean age was 54.4 years in study 1 and 56.9 years in study 2. The mean weight of patients in study 1 was higher than that in study 2 (88.8 vs 79.7 kg). The overall baseline mean sitting BP was 152.8/99.3 mm Hg in study 1 and 156.7/99.1 mm Hg in study 2. With the exception of a few combinations that included amlodipine 2.5 mg, the combination regimens in both studies were associated with significantly greater reductions in MSDBP and MSSBP compared with their individual components and placebo ( P P = 0.014), was significantly higher compared with valsartan monotherapy (2.1%; P Conclusions: In these adult patients with mild to moderate hypertension, the combination of amlodipine + valsartan was associated with significantly greater blood pressure reductions from baseline compared with amlodipine or valsartan monotherapy or placebo. The incidence of peripheral edema was significantly lower with combination therapy than with amlodipine monotherapy.