BACKGROUND: Previous studies using the combination of
angiotensin-receptor blockers and
hydrochlorothiazide (
HCTZ) have shown superior
ambulatory blood pressure (ABP) reduction in study participants with stage 2
hypertension compared with
monotherapy. OBJECTIVE: This multicenter,
double-blind, parallel group, forced-titration study of individuals with stage 2
hypertension, compared the efficacy of
valsartan and
amlodipine in combination with
HCTZ on ABP reduction. METHODS: After a 2-week washout period, participants (n=482) with
mean office sitting systolic BP >or=160 mmHg and <or=200 mmHg were
randomized to receive treatment with either
valsartan 160 mg (n=241) or
amlodipine 5 mg (n=241), force-titrated to a maximum dose of
valsartan/
HCTZ 320/25 mg or
amlodipine/
HCTZ 10/25 mg over 6 weeks and continued through week 10. The primary endpoint was change in
mean 24-h ambulatory systolic BP from baseline to week 10. RESULTS: At week 10, changes from baseline in
mean office BP were significantly (P<0.0001) decreased by both
valsartan/
HCTZ (-34.2/-14.2 mmHg) and
amlodipine/
HCTZ (-34.1/-14.7 mmHg). Changes from baseline in
mean 24-h ABP were significantly (P<0.0001) decreased by both
valsartan/
HCTZ (-21.1/-12.5 mmHg) and
amlodipine/
HCTZ (-18.1/-9.9 mmHg). However, treatment with
valsartan/
HCTZ provided significant additional systolic BP (-3.8 mmHg; P=0.0042) and
diastolic BP (-2.7 mmHg; P=0.0002) reduction compared with the
amlodipine/
HCTZ group. The proportion of individuals reaching the office goal BP (<140/80 mmHg) were similar in the
valsartan/
HCTZ (55.3%) versus
amlodipine/
HCTZ (54.9%) group, ABP control rates for the recommended ABP goal (<130/80 mmHg) were greater (P=0.0170) in the
valsartan/
HCTZ group (54.3%) than the
amlodipine/
HCTZ group (42.7%). Both treatments were well tolerated. CONCLUSION: On the basis of ABP monitoring but not office measurements, the fixed-dose combination of
valsartan/
HCTZ is a significantly more effective treatment regimen than
amlodipine/
HCTZ, with similar tolerability.
