Abstract
Objectives. To investigate the efficacy and tolerability of valsartan (Val) 320 mg once daily (o.d.), Val hydrochlorothiazide (HCTZ) 320 12.5 mg o.d. and Val HCTZ 320 25 mg o.d. in patients with hypertension not adequately controlled by Val monotherapy. Methods. This double-blind, active-controlled, parallel-group, randomized trial recruited patients 18 years with mild-to-moderate essential hypertension, defined as mean sitting diastolic blood pressure (MSDBP) of 95 mmHg and <110 mmHg without treatment. After washout, 3805 eligible patients received Val 320 mg o.d. single-blind for 4 weeks. Subsequently, patients with MSDBP 90 and <110 mmHg (n = 2702) were randomized to double-blind treatment with Val 320 mg, Val HCTZ 320 12.5 mg or Val HCTZ 320 25 mg for 8 weeks. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) from the start of the single-blind period were analysed, as well as the proportion of responders (MSDBP <90 mmHg or 10 mmHg decrease from the start of the double-blind period). Tolerability and safety were also assessed. Results. Reductions in MSDBP and MSSBP were observed in all groups. Both combinations were associated with significantly greater reductions than monotherapy for MSDBP and MSSBP at Weeks 8 and 12 (all p<0.0001). Both combinations also resulted in significantly greater proportion of responders at study end (74.9% and 68.8% for Val HCTZ 320 25 mg and Val HCTZ 320 12.5 mg, respectively) than monotherapy (52.7%; both p<0.0001). In addition, a dose-response was observed with increasing dose of HCTZ with respect to MSSBP. All treatments were well tolerated. Conclusions. The combination of Val and HCTZ at doses of 320 12.5 mg and 320 25 mg increases antihypertensive efficacy in patients with mild-to-moderate hypertension inadequately controlled with Val 320 mg monotherapy, without compromising tolerability.