Antihypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy

Abstract

This study investigated the addition of the direct renin inhibitor aliskiren to amlodipine in patients with mild to moderate hypertension that was inadequately controlled with amlodipine alone. Following once-daily treatment with amlodipine 5 mg for 4 weeks, patients whose hypertension responded inadequately to therapy (mean sitting diastolic blood pressure [DBP] 90-109 mm Hg) (n=545) were randomized to 6 weeks of double-blind treatment with amlodipine 5 mg plus aliskiren 150 mg, amlodipine 5 mg, or amlodipine 10 mg. At the study's end, mean systolic blood pressure and DBP reductions with the combination of aliskiren 150 mg and amlodipine 5 mg (11.0/8.5 mm Hg) were significantly greater (P<.0001) than with amlodipine 5 mg (5.0/4.8 mm Hg)--the comparator group--but similar to amlodipine 10 mg (9.6/8.0 mm Hg). All treatments were well tolerated. Edema occurred more frequently with amlodipine 10 mg (11.2%) than with combination therapy (2.1%) or amlodipine 5 mg (3.4%). In conclusion, aliskiren 150 mg plus amlodipine 5 mg shows similar but not better blood pressure-lowering efficacy when compared with amlodipine 10 mg in patients not completely responsive to amlodipine 5 mg; less edema was noted with combination therapy.

Figure 1

Patient flow. AEs indicates adverse events.

Figure 2

Change from baseline in mean sitting diastolic blood pressure (DBP) and mean sitting systolic blood pressure (SBP) at study end with once‐daily aliskiren 150 mg/amlodipine 5 mg, amlodipine 5 mg, and amlodipine 10 mg in hypertensive patients not responding (DBP ≥90 mm Hg and <110 mm Hg) to amlodipine 5 mg monotherapy (intent‐to‐treat population). *P<.0001 for aliskiren 150 mg/amlodipine 5 mg vs amlodipine 5 mg. †P=.0002 for amlodipine 10 mg vs amlodipine 5 mg (calculated retrospectively for completeness). Error bars indicate standard error of the mean.

Figure 3

Time course of mean sitting diastolic blood pressure (DBP) with once‐daily aliskiren 150 mg/amlodipine 5 mg, amlodipine 5 mg, and amlodipine 10 mg in hypertensive patients not responding to amlodipine 5 mg monotherapy (intent‐to‐treat population).

Figure 4

Change from baseline in plasma renin activity (PRA) at study end with once‐daily aliskiren 150 mg/amlodipine 5 mg, amlodipine 5 mg, and amlodipine 10 mg in hypertensive patients not responding to amlodipine 5 mg monotherapy (preselected subsection of study population).