Focus on atrial fibrillation

ABC Scores: assessment of biomarker levels over time allows for better prediction of embolic and bleeding events

The need for more precise and personalized risk prediction in patients with atrial fibrillation (AF) is undeniable. Biomarkers offer this possibility. Below, we summarize the Oyama et al. 2021 paper which reports that reassessment of the ABC risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk. This could allow for an exciting possibility of a new direction for monitoring patients with AF and a dynamic risk of future events.


Publication summary

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.

Oyama K, Giugliano RP, Berg DD, Ruff CT, Jarolim P, Tang M, Murphy SA, Lanz HJ, Grosso MA, Antman EM, Braunwald E, Morrow DA.

Atrial fibrillation patients (N=6308)


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Serial biomarker assessment: hs‑cTnT, NT‑proBNP, GDF‑15

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Monitored at baseline and 1 year


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Increases in biomarker levels over 1 year were associated with increased risk of:

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 Stroke or systemic embolism (hs-cTnT; NT-proBNP)

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Major bleeding (GDF-15)

Reassessment of ABC-bleeding or ABC-stroke scores at 1 year accurately reclassified a significant proportion of patients compared with baseline risk

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GDF-15, growth differentiation factor-15; hs-cTnT, high-sensitivity cardiac troponin T; NT-proBNP, N-terminal pro-B-type natriuretic peptide; ABC, age, biomarker, and clinical history



  • When combined with clinical parameters, biomarkers improve prediction of stroke and bleeding in trial-based cohorts of patients with atrial fibrillation (AF)1,2

  • A previous study demonstrated that the ABC (age, biomarkers, clinical history)-stroke and ABC-bleeding scores outperformed guideline-recommended3–5 CHA2DS2-VASc and HAS-BLED scores to predict stroke and bleeding.6
    Biomarker analysis of NT-proBNP, hs-cTnT and GDF-15 was performed on 8705 baseline samples from the ENGAGE AF-TIMI 48 trial, a double-blind randomized controlled trial of the oral factor Xa inhibitor edoxaban versus warfarin for the prevention of stroke and systemic embolism in patients with AF6,7

  • There is limited information, however, regarding variations in these biomarkers over the longer term and whether the fluctuations in biomarkers are subsequently associated with adverse clinical outcomes in patients with AF8

  • The objective of this study was to investigate whether patients with AF demonstrate detectable changes in NT-proBNP, hs-cTnT and GDF-15 over a 1-year period and whether variations from baseline to 12 months are associated with subsequent risk of stroke, systemic embolism or major bleeding8



  • A nested prospective biomarker analysis of NT-proBNP, hs-cTnT and GDF-15 biomarkers at baseline and 12 months was conducted in 6308 samples from patients enrolled in the ENGAGE AF-TIMI 48 trial, with a median follow-up of 2.8 years

  • Clinical outcomes of interest were the time to the first adjudicated stroke (ischemic and hemorrhagic), or systemic embolism, and adjudicated major bleeding during treatment. Major bleeding included the following fatal bleeding: 
    - Bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome 
    - Bleeding causing a fall in hemoglobin level of ≥2 g/dL (adjusted for transfusion) or leading to transfusion of ≥2U whole blood or red cells




  • At the 12-month time point a graded relationship between biomarker concentrations and outcomes was observed
    - Elevated NT-proBNP and hs-cTnT were independently associated with a greater than two-fold increased rate of subsequent stroke or systemic embolism (p<0.001)
    - Elevated GDF-15 was independently associated with a 1.76-fold higher rate of subsequent major bleeding (p<0.001)

  • Changes in biomarker concentrations between baseline and 12 months analyzed as a continuous variable were also independently associated with a risk of subsequent stroke, systemic embolism or bleeding
    - Patients with a two-fold increase in hs-cTnT or NT-proBNP from baseline to 12 months had 74% and 27% higher risks for stroke (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.36–2.23; p<0.001) and systemic embolism (HR 1.27; 95% CI 1.07–1.50; p=0.007), respectively 
    - Patients with a two-fold increase in GDF-15 over 12 months had a 40% higher risk for major bleeding (HR 1.40; 95% CI 1.02–1.92; p=0.037)

  • Reassessment of the ABC scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk for stroke or systemic embolism (net reclassification improvement [NRI] 0.50; 95% CI 0.36–0.65) and bleeding (NRI 0.42; 95% CI 0.33–0.51)
    - For example, patients with moderate risk for stroke, systemic embolism or bleeding at baseline who had a higher ABC scores at 12 months were be appropriately reclassified into a higher risk category


Clinical significance

  • A significant proportion of patients with AF had dynamic values in NT-proBNP, hs-cTnT and GDF-15 biomarkers between baseline and 12 months8

  • Serial biomarker-based risk assessment may allow clinicians to accurately monitor changes in risk over time, in line with the 2020 European Society of Cardiology guideline recommendations for the management of patients with AF9

  • Regular patient reassessment using ABC scores may represent a new strategy to dynamically monitor patients with AF for risk of future events and allow development of tailored therapeutic interventions8

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  2. Hijazi Z, et al. Lancet 2016;387:2302–11
  3. January CT, et al. Circulation 2014;130:2071–104
  4. Steffel J, et al. Eur Heart J 2018;39:1330–93 
  5. Kirchhof P, et al. Europace 2016;18:1609–78
  6. Berg DD, et al. Circulation 2019;139:760–71 
  7. Giugliano RP, et al. N Engl J Med 2013;369:2093–104
  8. Oyama K, et al. Eur Heart J 2021;42:1698–1706
  9. Hindricks G, et al. Eur Heart J 2021;42:373–498