N-Terminal Pro–B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation
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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).
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Measurement of cardiac troponin (high-sensitivity troponin T or I) and N-terminal pro-B-type natriuretic peptide may provide additional prognostic information in selected AF patients.
“Measurement of cardiac troponin (high-sensitivity troponin T or I) and N-terminal pro-B-type natriuretic peptide may provide additional prognostic information in selected AF patients.[380][381][382]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [381]
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- Authors
- Hijazi, Z., Wallentin, L., Siegbahn, A., Andersson, U., Christersson, C., Ezekowitz, J., Gersh, B. J., Hanna, M., Hohnloser, S., Horowitz, J., Huber, K., Hylek, E. M., Lopes, R. D., McMurray, J. J. V., & Granger, C. B.
- Affiliations
- Uppsala University (SE)
- University of Alberta (CA)
- Mayo Clinic (US)
- Bristol-Myers Squibb (United States) (US)
- Goethe University Frankfurt (DE)
- The University of Adelaide (AU)
- Wilhelminen Hospital (AT)
- Boston University (US)
- Western Infirmary (GB)
- Duke Medical Center (US)
- Corresponding author
- Hijazi, Ziad
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 61
- Issue
- 22
- Pages
- 2274-2284
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W189243586
- Cited by
- 231
- References
- 39
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 17 · 2023: 21 · 2022: 14 · 2021: 15 · 2020: 19 · 2019: 23 · 2018: 22 · 2017: 22 · 2016: 27 · 2015: 11 · 2014: 14 · 2013: 8
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Bristol-Myers Squibb, Co.
- Pfizer Inc.
- Bristol-Myers Squibb Co.
- Boehringer-Ingelheim
- AstraZeneca, Merck/Schering-Plough, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline
- AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, Schering-Plough
- Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough/Merck
- AstraZeneca and Boehringer-Ingelheim
- Bristol-Myers Squibb/Pfizer
- Alere, AstraZeneca, Amgen, Abbott, Servier, Johnson & Johnson, Pfizer, and Bristol-Myers Squibb
- sanofi-aventis, St. Jude Medical, Boehringer-Ingelheim, Cardiome, Pfizer, Bayer, and Bristol-Myers Squibb
- sanofi-aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Medtronic, and St. Jude Medical
- Bristol-Myers Squibb and Pfizer
- AstraZeneca, Bristol-Myers Squibb/Pfizer, Boehringer-Ingelheim, Bayer, Daiichi Sankyo, and sanofi-aventis
- Johnson & Johnson, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, and Ortho-McNeil-Janssen
- Boehringer Ingelheim and Bayer
- Bristol-Myers Squibb, AstraZeneca, Boehringer-Ingelheim, and Daiichi Sankyo
- Bristol-Myers Squibb and Boehringer-Ingelheim
- Bristol-Myers Squibb, Boehringer-Ingelheim, Astellas, AstraZeneca, GlaxoSmithKline, Medtronic Foundation, Merck, sanofi-aventis, and the Medicines Company
- Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, AstraZeneca, Eli Lily, GlaxoSmithKline, Hoffman-La Roche, Novartis, Otsuka, Sanofi-Aventis, and the Medicines Company
- Pfizer, Novartis, Otsuka, and Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- atrial fibrillation, apixaban, stroke risk stratification, CHA2DS2-VASc score, cardiovascular mortality, systemic embolism, risk prediction, ARISTOTLE trial, warfarin, bleeding risk, biomarkers, prognosis, natriuretic peptides, cardiovascular risk
- MeSH terms
- Aged, Anticoagulants, Atrial Fibrillation, Embolism, Female, Fibrinolytic Agents, Humans, Male, Peptide Fragments, Prognosis, Pyrazoles, Pyridones, Warfarin, Biomarkers, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Natriuretic Peptide, Brain, Stroke
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