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 tolerability of valsartan, a novel angiotensin II antagonist, given with hydrochlorothiazide (HCTZ) vs placebo or vs valsartan or HCTZ alone.


METHODS
871 adult out-patients with essential hypertension participated in this double-blind study. Patients were randomised in equal number to receive either combination therapy of valsartan (80 mg or 160 mg) and HCTZ (12.5 mg or 25 mg), or valsartan (80 mg or 160 mg) or HCTZ (12.5 mg or 25 mg) alone, or placebo. Patients were treated once daily for 8 weeks and assessed at 2, 4 and 8 weeks after randomisation.


METHODS
The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure (MSDBP) at end-point. The secondary variable was change in mean sitting systolic blood pressure (MSSBP) from baseline to end-point.


RESULTS
All active treatments produced a statistically significant difference 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 treatment-related adverse experiences reported. Hypokalaemia, associated with the use of thiazide diuretics, was more commonly reported in the higher dose 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. The addition of HCTZ to valsartan 80 mg or 160 mg was well tolerated.
Benz
J R
JR
Clinical Research, Cedar Rapids, IA 52401, USA.
Black
H R
HR
Graff
A
A
Reed
A
A
Fitzsimmons
S
S
Shi
Y
Y
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine