Evidence map›Paper›PMID 33760027›Full record

ArticleEuropean heart journal2021

Serial assessment of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial.

Kazuma Oyama, Robert P Giugliano, David D Berg, Christian T Ruff, Petr Jarolim, Minao Tang, Sabina A Murphy, Hans J Lanz, Michael A Grosso, Elliott M Antman and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Vascular cell adhesion molecule 1: a marker for atrial fibrillation and heart failure risk.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025
    Article
  4. Article
  5. Review
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  7. Article
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  9. Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Biomarker-based risk scores in atrial fibrillation.European heart journal. Acute cardiovascular care · 2021
    Article
  15. Review
  16. Review
  17. Review
  18. Atrial fibrillation.Nature reviews. Disease primers · 2016
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

Kazuma OyamaTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0002-4001-7312
Robert P GiuglianoTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0003-4110-7675
David D BergTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.
Christian T RuffTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.
Petr JarolimDivision of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.ORCID 0000-0002-9612-8652
Minao TangTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0002-4028-8534
Sabina A MurphyTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.
Hans J LanzDaiichi Sankyo, Zielstattstraße 48, München 81379, Germany.
Michael A GrossoDaiichi Sankyo, 211 Mt Airy Rd, Basking Ridge, NJ 07920, USA.
Elliott M AntmanTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0002-0808-9199
Eugene BraunwaldTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0002-3472-626X
David A MorrowTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.ORCID 0000-0002-9589-5382
Brigham and Women's Hospital · USDaiichi Sankyo (Germany) · DEDaiichi Sankyo (United States) · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
NCATS NIH HHS UL1 TR002541
6 · The paper itself

Abstract

aimsWe investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of stroke or systemic embolic events (S/SEE) and bleeding. METHODS AND

resultsENGAGE AF-TIMI 48 was a randomized trial of the oral factor Xa inhibitor edoxaban in patients with AF and a CHADS2 score of ≥2. We performed a nested prospective biomarker study in 6308 patients, analysing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/mL change), GDF-15 in 45.6% (≥300 pg/mL change) during 12 months. In a Cox regression model, upward changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE [adjusted hazard ratio (adj-HR) 1.74; 95% confidence interval (CI) 1.36-2.23 and adj-HR 1.27; 95% CI 1.07-1.50, respectively] and log2-transformed GDF-15 with bleeding (adj-HR 1.40; 95% CI 1.02-1.92). Reassessment of ABC-stroke (age, prior stroke/transient ischaemic attack, hsTnT, and NT-proBNP) and ABC-bleeding (age, prior bleeding, haemoglobin, hsTnT, and GDF-15) risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk [net reclassification improvement (NRI) 0.50; 95% CI 0.36-0.65; NRI 0.42; 95% CI 0.33-0.51, respectively].

conclusionSerial assessment of hsTnT, NT-proBNP, and GDF-15 revealed that a substantial proportion of patients with AF had dynamic values. Greater increases in these biomarkers measured over 1 year are associated with important clinical outcomes in anticoagulated patients with AF.

Indexed as

Atrial FibrillationEmbolismStrokeBiomarkersHumansInfantNatriuretic Peptide, BrainPeptide FragmentsProspective StudiesRisk AssessmentRisk FactorsBiomarkersNatriuretic Peptide, BrainPeptide FragmentsAtrial fibrillationBiomarkersHaemorrhageRisk assessmentStroke

Identifiers

PMID33760027
PMCPMC8599897
OpenAlexW3137991798

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.