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

Predictable dose-related efficacy is considered to be an important attribut e of any antihypertensive agent. To determine the magnitude of dose-respons ive efficacy for valsartan, a highly selective angiotensin II-receptor bloc ker, 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 40 67 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 al l nine studies, valsartan doses greater than or equal to 80 mg produced sta tistically significant reductions in supine or seated diastolic blood press ure (SDBP) and systolic blood pressure (SSBP) compared with placebo (P < 0. 05). The integrated analysis demonstrated a clear increase in blood-pressur e-lowering efficacy with increasing dose across the range 10 to 320 mg (pla cebo-subtracted mean changes from baseline to end point for valsartan 10, 2 0, 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 greater than or equal to 80 mg once daily.