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Background and Purpose— Current European guidelines for the management of atrial fibrillation suggest using biomarkers to refine the risk stratification process. However, it is unclear whether ≥2 biomarkers incrementally improve risk prediction beyond 1 biomarker alone. We investigated whether the predictive performance of CHA2 DS2 -VASc and HAS-BLED scores could be enhanced by incrementally adding consecutive different biomarkers in real-world atrial fibrillation patients taking vitamin K antagonists therapy.Methods— We included 940 atrial fibrillation patients stable on vitamin K antagonists (international normalized ratio, 2.0–3.0) for at least the previous 6 months. At inclusion, VWF (von Willebrand factor), high-sensitivity troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity IL (interleukin)-6, fibrin monomers, and BTP (β-trace protein) concentrations were quantified. During follow-up, all adverse events were recorded, and biomarkers were added to CHA2 DS2 -VASc and HAS-BLED scores depending on the C index.Results— During 6.5 (4.3–7.9) years, there were 98 ischemic strokes (1.60% per year) and 172 major bleeds (1.60% per year). After the addition of biomarkers, the predictive performance of CHA2 DS2 -VASc was not significantly increased, although the model with 3 biomarkers (ie, NT-proBNP+BTP+VWF) showed a low gain in sensitivity (integrated discrimination improvement, 2.70%;P &lt;0.001). The predictive performance of HAS-BLED was enhanced in all biomarker-based models, with the best prediction shown by the model with 3 biomarkers (ie, VWF+NT-proBNP+high-sensitivity IL-6; C index, 0.600 [95% CI, 0.561–0.625] versus 0.639 [95% CI, 0.607–0.669];P =0.025). This model also confirmed an increased sensitivity (integrated discrimination improvement, 5.20%;P &lt;0.001) and positive reclassification (net reclassification improvement, 19.20%;P =0.020).Conclusions— By adding consecutive biomarkers, the predictive ability of CHA2 DS2 -VASc for ischemic stroke was not increased, whereas the predictive ability of HAS-BLED for major bleeding was only slightly enhanced. The net benefit and clinical usefulness of the biomarker-based models were marginal in comparison to the original scores based on clinical factors.

Refining Stroke and Bleeding Prediction in Atrial Fibrillation by Adding Consecutive Biomarkers to Clinical Risk Scores