title: Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension.
abstract: OBJECTIVE
  To assess the antihypertensive efficacy and safety of the combination of the direct renin inhibitor aliskiren and ramipril in patients with diabetes and hypertension.
  
  
  METHODS
  In this double-blind, multicentre trial, 837 patients with diabetes mellitus and hypertension (mean sitting diastolic blood pressure [BP] > 95 and < 110 mmHg) were randomised to once-daily aliskiren (150 mg titrated to 300 mg after four weeks; n=282), ramipril (5 mg titrated to 10 mg; n=278) or the combination (n=277) for eight weeks. Efficacy variables were cuff mean sitting diastolic BP (msDBP) and mean sitting systolic BP (msSBP); 24-hour ambulatory BP, plasma renin activity (PRA) and plasma renin concentration (PRC) were also assessed.
  
  
  RESULTS
  At week 8, aliskiren, ramipril and aliskiren/ramipril lowered msDBP (mean+/-SEM) by 11.3+/-0.5, 10.7+/-0.5 and 12.8+/-0.5 mmHg, and msSBP by 14.7+/-0.9, 12.0+/-0.9 and 16.6+/-0.9 mmHg, respectively. Aliskiren/ramipril provided superior msDBP reductions to ramipril (p=0.004) or aliskiren (p=0.043) monotherapy; adding aliskiren to ramipril provided an additional mean BP reduction of 4.6/2.1 mmHg. Aliskiren monotherapy was non-inferior to ramipril for msDBP reduction (p=0.0002) and superior for msSBP reduction (p=0.021). All treatments significantly lowered mean 24-hour ambulatory BP. Aliskiren significantly reduced PRA from baseline as monotherapy (by 66%, p<0.0001) or in combination with ramipril (by 48%, p<0.0001), despite large increases in PRC in all treatment groups. Aliskiren was well tolerated as monotherapy or in combination with ramipril.
  
  
  CONCLUSIONS
  Combining aliskiren with ramipril provided a greater reduction in msDBP than either drug alone in patients with diabetes and hypertension.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Istanbul Medical Faculty, Istanbul, Turkey.
authors.forename: Yagiz
authors.initials: Y
authors.lastname: Uresin
authors.forename: Addison A
authors.initials: AA
authors.lastname: Taylor
authors.forename: Charles
authors.initials: C
authors.lastname: Kilo
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschöpe
authors.forename: Massimo
authors.initials: M
authors.lastname: Santonastaso
authors.forename: Ghionul
authors.initials: G
authors.lastname: Ibram
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.forename: Andrew
authors.initials: A
authors.lastname: Satlin
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D048909:Diabetes Complications / Q000188:drug therapy*; D003971:Diastole / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D001786:Blood Glucose; D005650:Fumarates; D017257:Ramipril; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren