title: Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure.
abstract: BACKGROUND
  Suppression of the renin-angiotensin-aldosterone system (RAAS) is therapeutically valuable in chronic heart failure (CHF). RAAS inhibition can be achieved in a number of ways though an orally active renin inhibitor (RI) has never been studied before. We describe the neurohumoral effects of an RI.
  
  
  RESULTS
  27 patients with NYHA class II or III CHF and an ejection fraction <or=0.35, were randomised to placebo, the ACE inhibitor ramipril or the RI aliskiren for 1 week after a 5-7 day washout period following ACE inhibitor withdrawal. Thereafter, patients were treated with either ramipril (target dose 10 mg qd) or aliskiren (target dose 300 mg qd) for a further 5 weeks. Plasma renin activity (PRA), angiotensin II, aldosterone and B-type natriuretic peptide (BNP) were measured at baseline (pre-randomisation), after one week and at two week intervals thereafter. The mean changes (%) at the end of the study (6 weeks), compared with baseline, were: PRA 164.9 (SD 149)% ramipril, -60.1 (24)% aliskiren (between groups p value<0.0001); angiotensin II 39.7 (138)% ramipril, -51.4 (40)% aliskiren (p<0.05); aldosterone -0.94 (67)% ramipril, 4.74 (60)% aliskiren (p=n.s.); BNP-7.51 (38)% ramipril, -1.79 (43)% aliskiren (p=n.s.).
  
  
  CONCLUSIONS
  Aliskiren appeared to suppress the RAAS as effectively as ramipril in the short term. RIs may offer an alternative therapeutic approach to the blockade of the RAAS.
authors.affiliation: Department of Cardiology, Western Infirmary, Glasgow, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Seed
authors.forename: Roy
authors.initials: R
authors.lastname: Gardner
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: Chris
authors.initials: C
authors.lastname: Hillier
authors.forename: David
authors.initials: D
authors.lastname: Murdoch
authors.forename: Robert
authors.initials: R
authors.lastname: MacFadyen
authors.forename: Alain
authors.initials: A
authors.lastname: Bobillier
authors.forename: Jessica
authors.initials: J
authors.lastname: Mann
authors.forename: Theresa
authors.initials: T
authors.lastname: McDonagh
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D000577:Amides / Q000627:therapeutic use*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017257:Ramipril / Q000627:therapeutic use; D012083:Renin / Q000097:blood; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000450:Aldosterone; D000577:Amides; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D005650:Fumarates; D020097:Natriuretic Peptide, Brain; D017257:Ramipril; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren