Effect of aliskiren addition to amlodipine on ankle edema in hypertensive patients: A three-way crossover study

Roberto Fogari, Annalisa Zoppi, Amedeo Mugellini, Pamela Maffioli, Pierangelo Lazzari, Claudio Monti, Giuseppe Derosa

Research output: Contribution to journalArticlepeer-review


Objective: The aim of this study was to assess the effect of aliskiren and amlopidine on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Research design and methods: After 4-week placebo, 120 outpatients with grade 1 - 2 hypertension were randomized to amlodipine 10 mg or aliskiren 300 mg or their combination for 8 weeks in three crossover periods. At the end of each treatment, blood pressure, AFV, PSTP, plasma renin activity (PRA) and norepinephrine were assessed. Results: Both monotherapies similarly reduced systolic blood pressure (SBP; p <0.001) and diastolic blood pressure (DBP; p <0.001), but the reduction was greater with amlodipine/aliskiren combination (SBP: - 24.6 mmHg, p <0.001 vs monotherapy; DBP: -20.9 mmHg, p <0.01 vs monotherapy). Amlodipine increased both AFV (+ 28.4%, p <0.01) and PSTP (+ 80.4%, p <0.01), while the combination produced a less marked increase in AFV (+ 6.6%, p <0.01 vs amlodipine) and PSTP (+ 20.1%, p <0.01 vs amlodipine). Plasma norepinephrine increased with amlodipine (+ 53.5%, p <0.01) and this increase was not reduced by aliskiren addition. PRA was unaffected by amlodipine, while it was reduced by both aliskiren monotherapy (- 77.7%, p <0.01) and aliskiren/amlodipine combination (- 75.7%, p <0.01). Conclusions: Direct renin inhibition by aliskiren partially counteracts the microcirculatory changes responsible for calcium-channel-induced edema formation, possibly through preferential vasodilation of venous capacitance vessels.

Original languageEnglish
Pages (from-to)1351-1358
Number of pages8
JournalExpert Opinion on Pharmacotherapy
Issue number9
Publication statusPublished - Jun 2011


  • Aliskiren
  • amlodipine
  • ankle edema
  • hypertension

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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