24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

Abstract

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg), valsartan/hydrochlorothiazide (320/25 mg), amlodipine/valsartan (10/320 mg) or amlodipine/hydrochlorothiazide (10/25 mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8 mm Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3 mm Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85 mm Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.

Trial registration: ClinicalTrials.gov NCT00327587.

Conflict of interest statement

Yves Lacourcière and David Calhoun received research funding from Novartis Pharmaceuticals Corporation for the current study. Robert Glazer, Joseph Yen and Nora Crikelair are employees of Novartis Pharmaceuticals Corporation.

Figures

Figure 1

Study design. Aml, amlodipine; HCTZ, hydrochlorothiazide; Val, valsartan.

Figure 2

Least squares mean change from baseline in 24-h, daytime and night time ambulatory (a) SBP and (b) DBP. Hexagons represent baseline values and circles represent end point values. Dotted lines indicate the upper end of the European Society of Hypertension/European Society of Cardiology target ranges for MASBP/MADBP (24 h: 125–130/80 mm Hg; daytime: 130–135/85 mm Hg; night time: 120/70 mm Hg). *P⩽0.0001 versus Aml/Val/HCTZ; **P⩽0.001 versus Aml/Val/HCTZ; ***P⩽0.01 versus Aml/Val/HCTZ. Aml, amlodipine; ESH/ESC, European Society of Hypertension/European Society of Cardiology; HCTZ, hydrochlorothiazide; MADBP, mean ambulatory diastolic blood pressure; MASBP, mean ambulatory systolic blood pressure; Val, valsartan.

Figure 3

Hourly MASBP (a) and MADBP (b) at baseline and end point over the 24-h dosing interval. Dotted lines indicate the upper end of the European Society of Hypertension/European Society of Cardiology target range for mean 24-h MASBP/MADBP (125–130/80 mm Hg). Aml, amlodipine; ESH/ESC, European Society of Hypertension/European Society of Cardiology; HCTZ, hydrochlorothiazide; MADBP, mean ambulatory diastolic blood pressure; MASBP, mean ambulatory systolic blood pressure; Val, valsartan.

Figure 4

Change from baseline in 24-h MASBP according to the severity of hypertension at baseline. Hexagons represent baseline values and circles represent end point values. Dotted line indicates the upper end of the European Society of Hypertension/European Society of Cardiology target range for mean 24-h MASBP (125–130 mm Hg). Aml, amlodipine; ESH/ESC, European Society of Hypertension/European Society of Cardiology; HCTZ, hydrochlorothiazide; MASBP, mean ambulatory systolic blood pressure; MSSBP, mean sitting systolic blood pressure; Val, valsartan.