title: N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).
abstract: OBJECTIVE
  This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.
  
  
  BACKGROUND
  Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.
  
  
  METHODS
  In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.
  
  
  RESULTS
  Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.
  
  
  CONCLUSIONS
  NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984).
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Ziad.Hijazi@ucr.uu.se
authors.forename: Ziad
authors.initials: Z
authors.lastname: Hijazi
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Christina
authors.initials: C
authors.lastname: Christersson
authors.forename: Justin
authors.initials: J
authors.lastname: Ezekowitz
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohnloser
authors.forename: John
authors.initials: J
authors.lastname: Horowitz
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D004617:Embolism / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D011720:Pyrazoles; D011728:Pyridones; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C522181:apixaban; D014859:Warfarin