title: Effect of aliskiren addition to amlodipine on ankle edema in hypertensive patients: a three-way crossover study.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Clinica Medica II, University of Pavia, Centro Ipertensione e Fisiopatologia Cardiovascolare, Department of Internal Medicine and Therapeutics , Pavia , Italy. r.fogari@unipv.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zoppi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Claudio
authors.initials: C
authors.lastname: Monti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D017311:Amlodipine / Q000008:administration & dosage*; D000842:Ankle / Q000473:pathology; D000843:Ankle Joint / Q000473:pathology; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004487:Edema / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D017311:Amlodipine; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D005650:Fumarates; D009638:Norepinephrine; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren