title: Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial.
abstract: OBJECTIVE
  Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.
  
  
  OBJECTIVE
  To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients.
  
  
  METHODS
  International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] ≥ 400 pg/mL or N -terminal pro-BNP [NT-proBNP] ≥ 1600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012.
  
  
  METHODS
  All patients received 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months. MAIN OUTCOME MEASURES Cardiovascular death or HF rehospitalization at 6 months and 12 months.
  
  
  RESULTS
  In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), β-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P = .41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P = .36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo.
  
  
  CONCLUSIONS
  Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00894387.
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. m-gheorghiade@northwestern.edu
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Fabio
authors.initials: F
authors.lastname: Baschiera
authors.forename: Jaco
authors.initials: J
authors.lastname: Botha
authors.forename: Tsushung A
authors.initials: TA
authors.lastname: Hua
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Gimpelewicz
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaumont
authors.forename: Anastasia
authors.initials: A
authors.lastname: Lesogor
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
mesh_terms: D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren