Effects of force-titrated valsartan/hydrochlorothiazide versus amlodipine/hydrochlorothiazide on ambulatory blood pressure in patients with stage 2 hypertension: the EVALUATE study

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 sifting systolic BP >= 160 mmHg and <= 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. Blood Press Monit 14:112-120 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.