title: Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial.
abstract: OBJECTIVE
  This double-blind study compared long-term efficacy, safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension.
  
  
  METHODS
  After a 2-4-week placebo run-in, 842 patients [mean sitting diastolic blood pressure (msDBP) 95-109 mmHg] were randomized to aliskiren 150 mg (n = 420) or ramipril 5 mg (n = 422). Dose titration (to aliskiren 300 mg/ramipril 10 mg) and subsequent hydrochlorothiazide addition (12.5 mg, titrated to 25 mg if required) were permitted at weeks 6, 12, 18 and 21 for inadequate blood pressure control. Patients completing the 26-week active-controlled treatment period were re-randomized to their existing regimen or placebo for a 4-week double-blind withdrawal phase.
  
  
  RESULTS
  Six hundred and eighty-seven patients (81.6%) completed the active treatment period. At week 26, aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure (17.9 versus 15.2 mmHg, P = 0.0036) and msDBP (13.2 versus 12.0 mmHg, P = 0.025), and higher rates of systolic blood pressure control (< 140 mmHg; 72.5 versus 64.1%, P = 0.0075) compared with ramipril-based therapy. During withdrawal, blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy; median blood pressure reached 140/90 mmHg after 1 and 4 weeks, respectively. Blood pressure reductions were maintained with continued active treatment. Aliskiren therapy was well tolerated. Overall adverse event rates were similar with aliskiren (61.3%) and ramipril (60.4%); cough was more frequent with ramipril (9.5%) than aliskiren (4.1%).
  
  
  CONCLUSIONS
  Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months, greater than those with ramipril-based therapy.
authors.affiliation: Department of Medicine, Division of Cardiology, Landspitali University Hospital, Reykjavik, Iceland. cardiac@simnet.is
authors.forename: Karl
authors.initials: K
authors.lastname: Andersen
authors.forename: Myron H
authors.initials: MH
authors.lastname: Weinberger
authors.forename: Brent
authors.initials: B
authors.lastname: Egan
authors.forename: Christian M
authors.initials: CM
authors.lastname: Constance
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Ali
authors.forename: James
authors.initials: J
authors.lastname: Jin
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Keefe
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000577:Amides / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage*; D012083:Renin / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D006852:Hydrochlorothiazide; D017257:Ramipril; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren