The combination of olmesartan medoxomil and Amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study

Background: Hypertension guidelines recommend the use of 2 agents having complementary mechanisms of action when > 1 agent is needed to achieve blood pressure (BP) goals. Objective: The aim of this study was to compare the efficacy and tolerability of combinations of olmesartan medoxomil (OM) and amlodipine besylate with those of the component monotherapies in patients with mild to severe hypertension. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, factorial study. Patients who were naive to antihypertensive therapy or who underwent a washout of previous antihypertensive therapy for up to 2 weeks and had a seated diastolic BP (SeDBP) of 95 to 120 mm Hg were randomized to receive 1 of the following for 8 weeks: OM 10, 20, or 40 mg; amlodipine (AML) 5 or 10 mg; each possible combination of OM and AML; or placebo. The primary end point was the change from baseline in SeDBP at week 8, with secondary end points including the change in seated systolic blood pressure (SeSBP), the proportion of patients reaching the BP goal (< 140/90 mm Hg; < 130/80 nun Hg for patients with diabetes), and the proportions of the intention-to-treat population reaching BP thresholds of < 120/80, < 130/80, < 130/85, and < 140/90 min Hg. Safety and tolerability were also evaluated, with a particular focus on the incidence and severity of edema. Results: Of the 1940 randomized patients, 54.3% were male. The mean age of the study population was 54.0 years and 19.8% were aged 65 years. The mean baseline BP was 164/102 mm Hg, and 79.3% of patients had stage 2 hypertension. Combination therapy with OM and AML was associated with dose-dependent reductions in SeDBP (from -13.8 mm Hg with OM/AML 1015 mg to -19.0 mm Hg with OM/AML 40/10 mg) and SeSBP (from -23.6 mm Hg with OM/AML 20/5 mg to -30.1 rum Hg with OM/AML 40/10 mg) that were significantly greater than the reductions with the corresponding component monotherapies (P < 0.001). At week 8, the number of patients achieving the BP goal ranged from 57 of 163 (35.0%) to 84 of 158 (53.2%) in the combination-therapy groups, from 32 of 160 (20.0%) to 58 of 160 (36.3%) in the OM monotherapy groups, and from 34 of 161 (21.1%) to 53 of 163 (32.5%) in the AML monotherapy groups (P < 0.005, combination therapies vs component monotherapies), compared with 14 of 160 (8.8%) in the placebo group. Achievement of the BP thresholds was highest in the combination-therapy groups, with 56.3% and 54.0% of patients achieving a BP < 140/90 mm. Hg with OM/AML 20/10 and 40/10 mg, respectively. Combination therapy was generally well tolerated, and no unexpected safety concerns emerged in the course of the study. The most common adverse events were edema (ranging from 9.9% [OM 20 mg] to 36.8% [AML 10 mg], compared with 12.3% with placebo) and headache (ranging from 2.5% [OM/AML 1015 mg] to 8.7% [OM 20 mg], compared with 14.2% with placebo). Conclusion: The combination of OM and AML was effective and well tolerated in this adult population with hypertension.