title: Effect of aliskiren in patients with heart failure according to background dose of ACE inhibitor: a retrospective analysis of the Aliskiren Observation of Heart Failure Treatment (ALOFT) trial.
abstract: OBJECTIVE
  To compare the effect of the direct renin inhibitor aliskiren on neurohumoral activity in heart failure patients treated with low-dose and high-dose ACE inhibitor.
  
  
  METHODS
  A retrospective analysis of the ALOFT trial. Comparison of the effects of 6 months treatment with aliskiren (versus placebo) in patients receiving <guideline-recommended dose of ACE inhibitor (n = 109) with those receiving ≥ recommended-dose (n = 81). Neurohumoral measures included B-type natriuretic peptide (BNP), NT proBNP, plasma renin activity and urinary aldosterone excretion.
  
  
  RESULTS
  Patients in each ACE inhibitor-dose group were generally similar (those in the ≥ recommended ACE inhibitor-dose had higher baseline blood-pressures and LVEF and were more often female and diabetic). In the <recommended-dose sub-group, the reduction in BNP from baseline to end-of-study was -1% (95% CI -32 to +44%) in the placebo-group and -32% (-1 to -53%) in the aliskiren group. The corresponding reductions in the ≥recommended ACE inhibitor-dose sub-group were: placebo -19% (-46 to +22%) and aliskiren -46% (-22 to -62%); interaction p-value 0.94. The pattern of results for other neurohumoral markers was similar.
  
  
  CONCLUSIONS
  Aliskiren causes neurohumoral suppression in heart failure, even in patients treated with ≥recommended-dose of ACE inhibitor.
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
authors.forename: Novalia P
authors.initials: NP
authors.lastname: Sidik
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Melanie
authors.initials: M
authors.lastname: Wright
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Gimpelewicz
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000652:urine; D000577:Amides / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; 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; D010446:Peptide Fragments / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D012083:Renin / Q000097:blood; D012189:Retrospective Studies; D016037:Single-Blind Method; D000092502:Renin Inhibitors
chemical_list: D000450:Aldosterone; D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D005650:Fumarates; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D012083:Renin; D000092502:Renin Inhibitors; C109794:pro-brain natriuretic peptide (1-76); C446481:aliskiren