Valsartan and hydrochlorothiazide in patients with essential hypertension.A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy

Objective: This study compares the antihypertensive efficacy and tolerabili ty of valsartan, a novel angiotensin ii antagonist, given with hydrochlorot hiazide (HCTZ) vs placebo or vs valsartan or HCTZ alone. Design: 871 adult out-patients with essential hypertension participated in this double-blind study. Patients were randomised in equal number to receiv e either combination therapy of vaisartan (80 mg or 180 mg) and HCTZ (12.5 mg or 25 mg), or valsartan (80 mg or 180 mg) or HCTZ (12.5 mg or 25 mg) alo ne, or placebo. Patients were treated once daily for 8 weeks and assessed a t 2, 4 and 8 weeks after randomisation. Main outcome measures: The primary efficacy variable was change from baseli ne in mean sitting diastolic blood pressure (MSDBP) at end-point. The secon dary variable was change in mean sitting systolic blood pressure (MSSBP) fr om baseline to end-point. Results: All active treatments produced a statistically significant differe nce in MSDBP (P < 0.001) from baseline to end-point compared with placebo. Similar results were obtained for MSSBP. All combination regimens produced a statistically significantly greater reduction in MSDPB and MSSBP than the corresponding monotherapies. Dizziness and headache were the most common t reatment-related adverse experiences reported. Hypokalaemia, associated wit h the use of thiazide diuretics, was more commonly reported in the higher d ose HCTZ 25 mg groups. Conclusions: Valsartan 80 mg and 160 mg act additively with HCTZ 12.5 mg or 25 mg to lower MSDBP and MSSBP in patients with essential hypertension. Th e addition of HCTZ to valsartan 80 mg or 160 mg was well tolerated.