Dose-response characteristics of olmesartan medoxomil and other angiotensin receptor antagonists

Angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are an effective initial antihypertensive monotherapy in many patients. However, when initial ARB monotherapy fails to achieve the recommended BP goal, there is some controversy as to whether dose uptitration or the addition of a diuretic is more appropriate. This article addresses this issue by reviewing the dose-response characteristics of olmesartan medoxomil and other ARBs, as well as the relationship between ARB uptitration and BP goal attainment. Two types of trial designs are used to assess dose response: dose-ranging studies (usually a parallel design using different doses across different patient groups), which are used to establish the optimal dose for US FDA registration purposes, and dose-titration studies (increased dosing within the same patients and treating to goal BP). Since dose titration is within the same patient, it may be considered more appropriate for demonstrating dose-response characteristics and demonstration of BP goal attainment. While results from dose-ranging studies suggest that the dose-response curve for some ARBs may be flat, dose-titration studies indicate that significant improvements in BP control and BP goal attainment can be achieved with ARB uptitration. In an integrated analysis of seven US and European randomized, placebo-controlled, dose-ranging trials involving 3055 patients with stage 2 hypertension treated with olmesartan medoxomil 2.5-80 mg/day or placebo for 8 weeks, all olmesartan medoxomil doses were significantly more effective than placebo in lowering the mean DBP and mean SBP (p