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

OBJECTIVES:

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: Ziad Hijazi, Lars Wallentin, Agneta Siegbahn, Ulrika Andersson, Christina Christersson, Justin Ezekowitz, Bernard J Gersh, Michael Hanna, Stefan Hohnloser, John Horowitz, Kurt Huber, Elaine M Hylek, Renato D Lopes, John J V McMurray, Christopher B Granger
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 61 Issue 22 Pg. 2274-84 (Jun 04 2013) ISSN: 1558-3597 [Electronic] United States
• PMID: 23563134 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticoagulants
• Biomarkers
• Fibrinolytic Agents
• Peptide Fragments
• Pyrazoles
• Pyridones
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• apixaban
• Warfarin

Topics

• Aged
• Anticoagulants (therapeutic use)
• Atrial Fibrillation (blood, drug therapy, mortality)
• Biomarkers (blood)
• Embolism (epidemiology)
• Female
• Fibrinolytic Agents (therapeutic use)
• Humans
• Male
• Multivariate Analysis
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Prognosis
• Proportional Hazards Models
• Pyrazoles (therapeutic use)
• Pyridones (therapeutic use)
• Risk Assessment
• Stroke (epidemiology, prevention & control)
• Warfarin (therapeutic use)