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.
OBJECTIVE
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 > or =18 years with mild-to-moderate essential hypertension, defined as mean sitting diastolic blood pressure (MSDBP) of > or =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 > or =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 > 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 ofVal 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.
Tuomilehto
Jaakko
J
Department of Public Health, University of Helsinki, Mannerheimintie 172, FIN-00300, Helsinki, Finland.
Tykarski
Andrzej
A
Baumgart
Peter
P
Reimund
Bernard
B
Le Breton
Stephanie
S
Ferber
Philippe
P
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068756:Valsartan; D014633:Valine