Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy

Abstract

Objectives: Many angiotensin receptor blocker (ARB) monotherapy patients need at least two agents to control blood pressure (BP). We investigated whether initiating intensive treatment with combination amlodipine/valsartan was superior to moderate treatment with amlodipine/valsartan in patients previously uncontrolled on ARB monotherapy.

Methods: In this 12-week study, patients aged at least 18 years on ARB (other than valsartan) for at least 28 days (with treatment-naïve patients or those not controlled on agents other than an ARB treated with open-label olmesartan 20 or 40 mg, respectively, for 28 days) and with uncontrolled mean sitting systolic blood pressure (MSSBP; ≥ 150-<200 mmHg) were randomized to amlodipine/valsartan 5/320 mg (n = 369) or 5/160 mg (n = 359). At week 2, the dose was increased to 10/320 mg in the intensive arm. Hydrochlorothiazide 12.5 mg was added to both arms at week 4. Optional up-titration with hydrochlorothiazide 12.5 mg at week 8 was allowed if MSSBP was more than 140 mmHg.

Results: At baseline, mean office sitting BP was comparable in the intensive (163.9/95.5 mmHg) and moderate (163.3/95.0 mmHg) groups. Intensive treatment provided greater BP reductions versus moderate treatment (P < 0.05) from week 4 (-23.0/-10.4 versus -19.2/-8.7 mmHg; primary endpoint) to week 12 (-29.0/-14.8 versus -25.3/-12.3 mmHg). Adverse events were reported by a similar percentage of patients in both groups (36.3% intensive, 37.6% moderate); peripheral edema was more common with intensive versus moderate treatment (8.7 versus 4.5%; P = 0.025).

Conclusions: Initiating treatment with an intensive dose of amlodipine/valsartan provides significantly greater BP lowering versus moderate treatment in hypertensive patients unresponsive to ARB monotherapy. Both treatment regimens were generally well tolerated based on adverse event reports, but the lack of routine laboratory testing after screening limits conclusions on tolerability.

Trial registration: ClinicalTrials.gov NCT00666536.

Figures

Fig. 1

Study design. HCTZ, hydrochlorothiazide.

Fig. 2

Patient disposition.

Fig. 3

Mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) during double-blind treatment with intensive treatment (single-pill amlodipine 10 mg/valsartan 320 mg) versus moderate treatment (single-pill amlodipine 5 mg/valsartan 160 mg). Hydrochlorothiazide (HCTZ) 12.5mg was added to both treatments at week 4, with optional additional HCTZ 12.5mg at week 8. Error bars represent standard error.

Fig. 4

Proportion of patients achieving blood pressure goal (P values are based on logistic regression.

Fig. 5

Mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) among patients with severe hypertension (baseline MSSBP ≥180mmHg) participating in the study. Error bars represent standard error.

Fig. 6

Mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) among patients at least 65 years of age (a) and below 65 years of age (b) participating in the study. Error bars represent standard error.