title: Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide.
abstract: OBJECTIVE
  Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed.
  
  
  METHODS
  A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers.
  
  
  RESULTS
  Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated.
  
  
  CONCLUSIONS
  Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ.
authors.affiliation: Fundapres, Las-Heras 2910-Piso 1A, Buenos Aires, Argentina. asvillamil@intramed.net
authors.forename: Alberto
authors.initials: A
authors.lastname: Villamil
authors.forename: Steven G
authors.initials: SG
authors.lastname: Chrysant
authors.forename: David
authors.initials: D
authors.lastname: Calhoun
authors.forename: Bonnie
authors.initials: B
authors.lastname: Schober
authors.forename: Huang
authors.initials: H
authors.lastname: Hsu
authors.forename: Linda
authors.initials: L
authors.lastname: Matrisciano-Dimichino
authors.forename: Jack
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000577:Amides; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D006852:Hydrochlorothiazide; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren