Combination therapy with valsartan/hydrochlorothiazide at doses up to 320/25 mg improves blood pressure levels in patients with hypertension inadequately controlled by valsartan 320 mg monotherapy.

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.