Ambulatory blood pressure response to triple therapy with an angiotensin-receptor blocker (ARB), calcium-channel blocker (CCB), and HCTZ versus dual therapy with an ARB and HCTZ

Abstract

Background: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for assessing antihypertensive drugs and their combinations.

Objective: To compare the effect of a moderate dose of angiotensin receptor blocker/calcium channel blocker (ARB/CCB) combined with a diuretic versus a maximal dose of ARB with a diuretic on 24-hour ambulatory blood pressure monitoring (ABPM) and other derived ambulatory blood pressure (ABP) parameters.

Methods: The EXforge As compared to Losartan Treatment ABPM substudy was a randomized, double-blind, parallel-group, active-control, forced-titration study of patients with Stage 2 hypertension that compared the efficacy of initial treatment with valsartan/amlodipine 160/5 mg (n = 48) or losartan 100 mg (n = 36). At week 3, hydrochlorothiazide (HCTZ) 25 mg was added in both treatment groups. ABP was measured at baseline and at week 6. Additionaly, 24-hour ABP, nighttime (10 pm to 6 am) and daytime (6 am to 10 pm) ABP, and ABP load (percentage of readings above 140/90 mmHg) were determined.

Results: Eighty-four patients (48 ARB/CCB/HCTZ, 36 ARB/HCTZ) had ABPM at baseline and at week 6. Reductions of systolic/diastolic ABP were greater in the ARB/CCB/ HCTZ group than in the ARB/HCTZ group for 24-hour mean ABP (-22.0/-13.3 versus -17.4/-8.1 mmHg), as well as nighttime ABP (-22.2/-13.3 versus -16.2/-7.4 mmHg), daytime ABP (-21.9/-13.0 versus -18.1/-8.6 mmHg), ABP in the last 4 hours of the dosing period (-21.5/-13.5 versus -17.0/-7.7 mmHg), and ABP load (21.7%/12.8% versus 30.8%/20.0%).

Conclusion: Initiating antihypertensive treatment with moderate doses of ARB/CCB with a diuretic is more effective in lowering nighttime and daytime ABP and reducing ABP load than a maximal dose of an ARB with a diuretic.

Keywords: ambulatory blood pressure; ambulatory blood pressure monitoring; amlodipine; antihypertensive drugs; combination therapy; hydrochlorothiazide; losartan; valsartan.

Figure 1

ABPM substudy design. Study medication was force titrated at week 3. ABP was measured for 24 hours before the visits at week 0 and week 6. Note: *ABPM was conducted for 24 hours prior to the week-0 and week-6 visits. Abbreviations: ABP, ambulatory blood pressure; ABPM, ambulatory blood pressure monitoring; HCTZ, hydrochlorothiazide.

Figure 2

LSM change from baseline to week 6 in ABP. Changes were evaluated for the 24-hour mean values, the average of nighttime values (from 10 pm to 6 am), the average of daytime values (from 6 am to 10 pm), and the average values during the last 4 hours before the next dose of study medication. Notes: Least-square mean differences between treatment groups are shown below the bars. *P < 0.05 by ANCOVA with baseline ABP and treatment regimen as explanatory variables. Abbreviations: ABP, ambulatory blood pressure; HCTZ, hydrochlorothiazide; ANCOVA, analysis of covariance; LSM, least squares mean.

Figure 3

Mean hourly ambulatory blood pressure (ABP) at baseline and at week 6; (A) systolic ABP; (B) diastolic ABP. Abbreviation: HCTZ, hydrochlorothiazide.

Figure 4

Mean ambulatory blood pressure (ABP) load at baseline and at week 6. Systolic ABP load and diastolic ABP load were defined as the percentage of readings (during the 24-hour ABP monitoring) that were >140 mmHg and >90 mmHg, respectively. Abbreviations: HCTZ, hydrochlorothiazide; ANCOVA, analysis of covariance.