Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II—receptor blocker

Abstract

Predictable dose-related efficacy is considered to be an important attribute of any antihypertensive agent. To determine the magnitude of dose-responsive efficacy for valsartan, a highly selective angiotensin II—receptor blocker, we conducted an integrated analysis of efficacy data from nine double-masked, randomized, placebo-controlled, parallel studies of similar design and of at least 4 weeks' duration. The intent-to-treat analysis included 4067 patients with mild-to-moderate hypertension who had received valsartan (n = 2901) 10, 20, 40, 80, 160, or 320 mg once daily or placebo (n = 1166). Blood pressure was assessed at trough (24 hours after the last dose). In all nine studies, valsartan doses ≥80 mg produced statistically significant reductions in supine or seated diastolic blood pressure (SDBP) and systolic blood pressure (SSBP) compared with placebo ( P < 0.05). The integrated analysis demonstrated a clear increase in blood-pressure—lowering efficacy with increasing dose across the range 10 to 320 mg (placebo-subtracted mean changes from baseline to end point for valsartan 10, 20, 40, 80, 160, and 320 mg, respectively: SDBP, −0.8, −2.8, −2.6, −3.9, −5.1, and −6.4 mm Hg; SSBP, −1.3, −5.7, −5.3, −6.8, −8.6, and −9.0 mm Hg). The data demonstrate that valsartan provides dose-responsive antihypertensive efficacy across the therapeutic dose range, with clinically relevant blood-pressure lowering at doses ≥80 mg once daily.