Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension

Background: Most patients with hypertension in the United States and Europe fall to achieve the recommended target blood pressure (BP) of < 140/90 mm Hg. Combination therapy is required in approximately two thirds of all patients whose BP is > 20/10 mm Hg above the goal. Combination therapy with agents having complementary mechanisms of action, such as a calcium channel blocker and an angiotensin II-receptor blocker, would be a potentially useful therapeutic option. Objectives: This study evaluated the overall safety profile of combination therapy with amlodipine plus valsartan compared with a combination of lisinopril plus hydrochlorothiazide (HCTZ) in patients with stage 2 hypertension (mean sitting diastolic BP [MSDBP] >= 110 and < 120 mm Hg) over the short term (6 weeks). A secondary objective was to evaluate the efficacy of the 2 regimens in achieving BP reduction. Methods: This was an international, multicenter, randomized, double-blind, active-controlled, parallel-group study. Patients were randomized to receive once-daily treatment with amlodipine 5 to 10 mg + valsartan 160 mg or lisinopril 10 to 20 mg + HCTZ 12.5 mg for 6 weeks. Safety assessments included monitoring of all adverse events, vital signs, and hematology and biochemistry variables. Efficacy variables included the changes from baseline in MSDBP and mean sitting systolic BP (MSSBP), the response rate (MSDBP < 90 mm Hg, or a >= 10-mm Hg reduction from baseline), and the rate of DBP control (< 90 mm Hg). The overall rate of BP control (proportion of patients with MSSBP/MSDBP < 140/90 min Hg) was evaluated in a post hoc analysis. Efficacy variables were summarized at each visit and at the end of the study (week 6, applying last-observation-carried-forward methodology) using descriptive statistics for the intent-to-treat population (all randomized patients with a baseline BP measurement and at least 1 postbaseline BP measurement). Subgroup analyses of BP changes were performed in prespecified age groups (< 65 and >= 65 years) and post hoc in patients with a baseline systolic BP < 180 and >= 180 mm Hg. Results: Of 130 patients who were randomized to treatment, 128 completed the study: 63 in the amlodipine + valsartan group and 65 in the lisinopril + HCTZ group. The majority of patients in both groups were white (amlodipine + valsartan: 59.4%; lisinopril + HCTZ: 60.6%) and female (57.8% and 54.5%, respectively). The mean age was similar in the 2 groups (56.5 and 57.6 years), as was the mean weight (85.1 and 82.0 kg). Both regimens were generally well tolerated. Adverse events were mild to moderate in severity, and most were not considered related to study drug. At the 6-week end point, both the amlodipine + valsartan and lisinopril + HCTZ groups had achieved significant reductions from baseline in MSSBP (-35.8 [11.8] and -31.8 [14.7] min Hg, respectively; both, P < 0.001) and MSDBP (-28.6 [7.7] and -27.6 [8.6] mm Hg; both, P < 0.001). Response rates were similar for the 2 treat-ment groups (100% and 95.5%), as were rates of DBP control (79.7% and 77.3%). Conclusions: The combinations of amlodipine 5 to 10 mg + valsartan 160 mg and lisinopril 10 to 20 mg + HCTZ 12.5 mg were well tolerated and efficacious, and both treatments were associated with achievement of BP goals in the majority of these adult patients with stage 2 hypertension.