title: Long-term antihypertensive efficacy and safety of the oral direct renin inhibitor aliskiren: a 12-month randomized, double-blind comparator trial with hydrochlorothiazide.
abstract: BACKGROUND
  Diuretics are recommended as first-line agents for the treatment of hypertension. This randomized, double-blind, multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension.
  
  
  RESULTS
  After a 2- to 4-week placebo run-in, 1124 patients (mean sitting diastolic blood pressure [BP] 95 to 109 mm Hg) were randomized to aliskiren 150 mg (n=459), hydrochlorothiazide 12.5 mg (n=444), or placebo (n=221) once daily. Forced titration (to aliskiren 300 mg or hydrochlorothiazide 25 mg) occurred at week 3; at week 6, patients receiving placebo were reassigned (1:1 ratio) to aliskiren 300 mg or hydrochlorothiazide 25 mg. From week 12, amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled. Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method. BP reductions (mean sitting systolic BP/mean sitting diastolic BP) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 (-20.3/-14.2 versus -18.6/-13.0 mm Hg; P<0.05) and were also greater at week 52 (-22.1/-16.0 versus -21.2/-15.0 mm Hg; P<0.05 for mean sitting diastolic BP). At the end of the monotherapy period (week 12), aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP (-17.4/-12.2 versus -14.7/-10.3 mm H; P<0.001). Adverse event rates were similar with aliskiren- (65.2%) and hydrochlorothiazide-based therapy (61.5%). Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy (17.9% versus 0.9%; P<0.0001).
  
  
  CONCLUSIONS
  Aliskiren treatment, both as monotherapy and with optional addition of amlodipine, provided significantly greater BP reductions than the respective hydrochlorothiazide regimens. Aliskiren-based therapy was well tolerated. Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany. Roland.Schmieder@rzmail.uni-erlangen.de
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
authors.forename: Thomas
authors.initials: T
authors.lastname: Philipp
authors.forename: Javier
authors.initials: J
authors.lastname: Guerediaga
authors.forename: Manuel
authors.initials: M
authors.lastname: Gorostidi
authors.forename: Beverly
authors.initials: B
authors.lastname: Smith
authors.forename: Nicole
authors.initials: N
authors.lastname: Weissbach
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Maboudian
authors.forename: Jaco
authors.initials: J
authors.lastname: Botha
authors.forename: Hein
authors.initials: H
authors.lastname: van Ingen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004415:Dyspepsia / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D005650:Fumarates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000502:physiology; D016037:Single-Blind Method; D013995:Time; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D006852:Hydrochlorothiazide; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren