Randomized study to compare valsartan +/- HCTZ versus amlodipine +/- HCTZ strategies to maximize blood pressure control

Dion Zappe, Cheraz Cherif Papst, Philippe Ferber, PROMPT Investigators, Dion Zappe, Cheraz Cherif Papst, Philippe Ferber, PROMPT Investigators

Abstract

Objective: Delays in achieving blood pressure (BP) control may increase morbidity and mortality in patients with hypertension. Thus, deciding which antihypertensive agent to use and at what dosage, in addition to determining when to initiate combination therapy and which agents to combine, is important for achieving BP control.

Methods: This randomized, double-blind, 14-week study was conducted to compare the efficacy and tolerability of various doses of valsartan +/- hydrochlorothiazide (HCTZ) versus amlodipine +/- HCTZ for maximizing BP control in 1,285 patients with uncontrolled hypertension. Patients with stage 1 hypertension and naïve to antihypertensive therapy (33.9%) started valsartan 160 mg or amlodipine 5 mg. Treatment-naïve patients with stage 2 hypertension (13.5%) or those uncontrolled on current antihypertensive monotherapy (52.6%) started valsartan 160 mg/HCTZ 12.5 mg or amlodipine 10 mg. At weeks 4, 8, and 11, patients not achieving BP control were up-titrated (maximum: valsartan 320 mg/HCTZ 25 mg, amlodipine 10 mg/HCTZ 25 mg).

Results: At study end, 78.8% of patients on valsartan +/- HCTZ were controlled (BP <140/90 mmHg) and still on study medication versus 67.8% on amlodipine +/- HCTZ (P < 0.0001). Amlodipine-treated patients had a higher incidence of peripheral edema (22.4% vs 2.2%) and associated discontinuations (7.3% vs <1%). Initiating therapy earlier with valsartan/HCTZ, rather than titrating monotherapy to its maximum dose before adding a second agent, was superior to amlodipine monotherapy or amlodipine +/- HCTZ for achieving BP control, and avoided excessive treatment adjustments and maintained tolerability.

Keywords: combination therapy; efficacy; hydrochlorothiazide; hypertension; titration; tolerability.

Figures

Figure 1
Figure 1
Study design. Abbreviations: Amlo, amlodipine; HCTZ, hydrochlorothiazide; Val, valsartan.
Figure 2
Figure 2
Patient disposition.
Figure 3
Figure 3
Percentage of patients who achieved blood pressure (BP) control (mean sitting systolic/diastolic BP

Figure 4

Percentage of patients on each…

Figure 4

Percentage of patients on each treatment regimen at week 11, the last up-titration…

Figure 4
Percentage of patients on each treatment regimen at week 11, the last up-titration visit. Percentages may not add up to 100 due to rounding. Numbers on x-axis represent doses (in mg) of valsartan, valsartan/hydrochlorothiazide (HCTZ), amlodipine, and amlodipine/HCTZ. Abbreviation: DC, discontinuation.
Figure 4
Figure 4
Percentage of patients on each treatment regimen at week 11, the last up-titration visit. Percentages may not add up to 100 due to rounding. Numbers on x-axis represent doses (in mg) of valsartan, valsartan/hydrochlorothiazide (HCTZ), amlodipine, and amlodipine/HCTZ. Abbreviation: DC, discontinuation.

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