The role of ambulatory blood pressure monitoring compared with clinic and home blood pressure measures in evaluating moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy

Abstract

Objectives: Ambulatory blood pressure monitoring (ABPM) has greater predictive value than office blood pressure (BP) with respect to hypertension-related target-organ damage and morbidity. ABPM in a subset of 80 patients from the Exforge Target Achievement trial (N=728) was used to compare the efficacy of intensive-treatment and moderate-treatment regimens of amlodipine/valsartan, and to determine whether treatment differences could be better assessed with ABPM than with office or home BP. Home BP was measured on the morning of clinic visits to minimize differences that timing might have on home versus office BP measures.

Methods: A 12-week randomized, double-blind study in which hypertensive patients earlier uncontrolled (mean sitting systolic BP≥150 and <200 mmHg) on angiotensin receptor blocker monotherapy (other than valsartan) after 28 days or more (N=728) were randomized to amlodipine/valsartan treatment [10/320 mg (intensive) or 5/160 mg (moderate)]. Treatment-naive patients (in previous 28 days) or patients who failed on a nonangiotensin receptor blocker agent underwent a 28-day run-in period with a 20-mg or 40-mg dose of olmesartan, respectively.

Results: Significantly greater 24-h ABP reductions from baseline to week 4 (primary time point) were observed with intensive versus moderate treatment (least-square mean systolic/diastolic BP reduction of -16.2/-10.1 vs. -9.5/-6.5 mmHg; P=0.0024/P=0.010 for least-square mean difference). Similarly, a significantly greater proportion of patients receiving an intensive treatment achieved ambulatory BP goal (<130/80 mmHg) at week 4 than did those receiving a moderate treatment (P=0.040). Treatment-group differences did not reach statistical significance for these end points when measured by office and home BP.

Conclusion: In this first randomized trial evaluating the effects of intensive versus moderate dosing of the combination of amlodipine/valsartan, our data suggest that ABPM was a better method for assessing between-treatment differences than clinic or home BP recordings, although measurement of home BP as a single recording was a limitation of our trial.

Trial registration: ClinicalTrials.gov NCT00666536.

Figures

Fig. 1

Study design. ABPM, ambulatory blood pressure monitoring; HCTZ, hydrochlorothiazide. Reproduced with permission from [13].

Fig. 2

Least-square mean (LSM) reductions from baseline in 24-h ambulatory, clinic, and home systolic blood pressure (SBP, a) and diastolic blood pressure (DBP, b) during intensive treatment (amlodipine/valsartan =10/320 mg) versus moderate treatment (amlodipine/valsartan =5/160 mg) in the ambulatory blood pressure monitoring substudy population. Hydrochlorothiazide (12.5 mg) was added to both treatments at week 4, with optional additional hydrochlorothiazide 12.5mg at week 8. Error bars represent standard error. *P<0.05; **P<0.01 vs. moderate treatment. ADBP, ambulatory diastolic blood pressure; ASBP, ambulatory systolic blood pressure.

Fig. 3

Hourly ambulatory systolic blood pressure (ASBP) and ambulatory diastolic blood pressure (ADBP) after 12 weeks of intensive treatment (amlodipine/valsartan =10/320 mg) versus moderate treatment (amlodipine/valsartan =5/160mg) in the ambulatory blood pressure (ABP) monitoring substudy population. The first dose hour starts at 09:00h. Hydrochlorothiazide (12.5 mg) was added to both treatments at week 4, with optional additional hydrochlorothiazide 12.5mg at week 8.

Fig. 4

Proportion of patients achieving ambulatory, clinic, and home blood pressure (BP) goals during intensive treatment (amlodipine/valsartan = 10/ 320 mg) versus moderate treatment (amlodipine/valsartan= 5/160 mg) in the ambulatory blood pressure monitoring (ABPM) substudy population. Hydrochlorothiazide (HCTZ, 12.5 mg) was added to both treatments at week 4, with optional additional HCTZ 12.5 mg at week 8. By week 12, 127 (35%) patients in the intensive arm and 170 (48%) patients in the moderate arm were receiving 25 mg of HCTZ. This likely contributed to the lack of significant differences between the two treatment arms at week 12. P values are based on logistic regression. *P<0.05 vs. moderate treatment.