title: Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.
abstract: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear.
  
  
  
  This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152).
  
  
  
  In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Ahmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Haris P
authors.initials: HP
authors.lastname: Subacius
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Ambrosy
authors.affiliation: Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.affiliation: INSERM, CHRU Nancy, Université de Lorraine, Centre d'Investigation Clinique CIC1433, F54000, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Division of Cardiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000368:Aged; D000577:Amides / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications; D001282:Atrial Flutter / Q000097:blood / Q000150:complications; D018450:Disease Progression; D005260:Female; D005650:Fumarates / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C446481:aliskiren
keywords: Atrial fibrillation; Heart failure; Natriuretic peptide; Outcomes