title: Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.
abstract: OBJECTIVE
  The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).
  
  
  RESULTS
  ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction).
  
  
  CONCLUSIONS
  This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.
authors.affiliation: Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Fabio
authors.initials: F
authors.lastname: Baschiera
authors.forename: Tsushung A
authors.initials: TA
authors.lastname: Hua
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Gimpelewicz
authors.forename: Anastasia
authors.initials: A
authors.lastname: Lesogor
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D002316:Cardiotonic Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren
keywords: Aliskiren; Diabetes; Outcomes; Post-discharge