Research in context
Evidence before this study
Bleeding risk scores are important clinical instruments to balance the risk of bleeding events against the risk of stroke during anticoagulant treatment in atrial fibrillation. However, current guideline recommended bleeding scores only have a modest predictive ability. During the past years, several biomarkers reflecting cardiovascular and renal physiology, coagulation, and inflammatory activity have shown association with risk of major bleeding in patients with atrial fibrillation. A risk score for major bleeding in atrial fibrillation using both clinical risk factors and prognostic biomarkers could improve the risk assessment and clinical usefulness.
We have previously reviewed data for biomarkers and risk of cardiovascular events in patients with atrial fibrillation. We updated our review of this topic with added focus on risk of major bleeding. We searched PubMed without language or date restrictions for publications up to February, 2016, about bleeding risk in atrial fibrillation and biomarkers of renal and cardiovascular physiology as well as biomarkers of coagulation and inflammatory activity, included free-text search terms such as “atrial fibrillation”, “biomarkers”, “major bleeding”, “renal function”, “cystatin C”, “cardiac biomarkers”, “troponin”, “GDF-15, “, “coagulation”, “D-dimer”, “inflammation”, “CRP”, and “IL-6” in various combinations. No language or date restrictions were enabled. Several of these biomarkers were associated with major bleeding risk in patients with atrial fibrillation on oral anticoagulation. In particular, GDF-15, cardiac troponin, and markers of renal dysfunction showed robust associations with the outcome. However, development and validation of a risk score including the prognostically most important biomarkers and clinical characteristics for major bleeding risk in atrial fibrillation has not previously been done.
Added value of this study
In this study, a novel risk score for prediction of major bleeding events using age, history of bleeding, and the level of three biomarkers (GDF-15, cTn-hs, and haemoglobin) was developed and internally and externally validated and was calibrated in two large cohorts of patients with atrial fibrillation treated with oral anticoagulation. The ABC-bleeding score, containing the variables (age, biomarkers, clinical history [previous bleeding]), showed better discrimination and use than the HAS-BLED score. Although the study also provided external validation of the superiority of the recently presented ORBIT bleeding score in comparison to the HAS-BLED score in both these large cohorts, the ABC-bleeding score also did better than the ORBIT score. The ABC score should therefore be useful as decision support regarding indications for and selection of treatment with oral anticoagulation treatment in patients with atrial fibrillation.
Importantly, the biomarkers included in the score, cardiac troponin, GDF-15, or cystatin C, and haemoglobin or haematocrit, are already, or will be (GDF-15), generally available in many parts of the world, which enables a wide clinical use of the new score. Furthermore, and by contrast with previous scores, which use mainly irreversible risk factors, the proposed ABC-bleeding score contains continuous biomarker concentrations, which over time might increase or decrease reflecting changes in the patient's cardiovascular condition and therefore provides additional unique features for personalised risk assessment.
Implications of all the available evidence
This study brings new insights to clinical physicians by providing a fundamentally new and improved model to predict the risk of bleeding in atrial fibrillation and could accordingly provide improved decision support in these patient populations.