Journal of Interventional Cardiac Electrophysiology

, Volume 40, Issue 3, pp 277–284 | Cite as

Performance of the HAS-BLED high bleeding-risk category, compared to ATRIA and HEMORR2HAGES in patients with atrial fibrillation: a systematic review and meta-analysis

  • Daniel CaldeiraEmail author
  • João Costa
  • Ricardo M. Fernandes
  • Fausto J. Pinto
  • Joaquim J. Ferreira



Atrial fibrillation (AF) patients’ major bleeding risk should be evaluated through risk scores such as HAS-BLED, HEMORR2HAGES or ATRIA. These scores were validated in independent studies with different methods. Therefore, we aimed to review and estimate the value added by ATRIA and HEMORR2HAGES compared to HAS-BLED.


Medline and Cochrane Library (July 2013) were searched, as well as reviews and references of obtained articles. We looked for studies reporting data for diagnostic accuracy of HAS-BLED with any of HEMORR2HAGES or ATRIA scores, concerning Major Bleeding events. We determined the sensitivity, specificity, and diagnostic odds ratio (DOR) of ATRIA and HEMORR2HAGES compared to HAS-BLED within the same studies. Random effects meta-analysis was performed in order to derive diagnostic accuracy estimates. Heterogeneity was assessed through I 2 test.


Six studies fulfilled inclusion criteria. Five studies evaluated simultaneously HAS-BLED and HEMORR2HAGES. Sensitivity, specificity, and DOR were respectively 0.53 (0.52–0.54), 0.65 (0.65–0.65) and 2.11 (1.91–2.35) for HAS-BLED, and 0.27 (0.26–0.27), 0.89 (0.89–0.89) and 2.90 (2.77–3.04) for HEMORR2HAGES. Four studies compared HAS-BLED with ATRIA. Sensitivity, specificity, and DOR were respectively 0.41 (0.35–0.48), 0.78 (0.76–0.79) and 2.22 (1.08–4.55) for HAS-BLED, and 0.23 (0.17–0.29), 0.91 (0.90–0.91) and 1.98 (1.29–3.03) for ATRIA.


The ‘high-risk’ categories of the evaluated major bleeding-risk scores are not sensitive. HAS-BLED, due to its sensitivity (compared to other scores) and ease to apply, is recommended for the assessment of AF patients’ major bleeding risk.


Bleeding Hemorrhage Score system Clinical prediction rule HAS-BLED 




Conflict of interest

DC, JC and RMF do not have any competing interests to disclose. JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, Lundbeck, Solvay, Abbott, Bial, Grunenthal, and Merck Sharp and Dohme. FJP had consultant and speaker fees with Astra Zeneca, Bayer and Boehringer Ingelheim.

Supplementary material

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Supplementary Figure 1

Flowchart of studies selection. (GIF 881 kb)

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High resolution image (TIFF 184 kb)
10840_2014_9930_MOESM2_ESM.pdf (126 kb)
ESM 1 (PDF 126 kb)


  1. 1.
    Lip, G. Y., Andreotti, F., Fauchier, L., Huber, K., Hylek, E., Knight, E., et al. (2011). Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis. Europace, 13, 723–746.PubMedCrossRefGoogle Scholar
  2. 2.
    Camm, A. J., Kirchhof, P., Lip, G. Y., Schotten, U., Savelieva, I., Ernst, S., et al. (2010). Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace, 12(10), 1360–1420.PubMedCrossRefGoogle Scholar
  3. 3.
    Camm, A. J., Lip, G. Y., De Caterina, R., Savelieva, I., Atar, D., & Hohnloser, S. H. (2012). 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association. Europace, 14, 1385–1413.PubMedCrossRefGoogle Scholar
  4. 4.
    Hart, R. G., Benavente, O., McBride, R., & Pearce, L. A. (1999). Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Annals of Internal Medicine, 131, 492–501.PubMedCrossRefGoogle Scholar
  5. 5.
    Miller, C. S., Grandi, S. M., Shimony, A., Filion, K. B., & Eisenberg, M. J. (2012). Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. The American Journal of Cardiology, 10, 453–460.CrossRefGoogle Scholar
  6. 6.
    Andersen, L. V., Vestergaard, P., Deichgraeber, P., Lindholt, J. S., Mortensen, L. S., & Frost, L. (2008). Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis. Heart, 94, 1607–1613.PubMedCrossRefGoogle Scholar
  7. 7.
    Agarwal, S., Hachamovitch, R., & Menon, V. (2012). Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Archives of Internal Medicine, 172, 623–631.PubMedCrossRefGoogle Scholar
  8. 8.
    Pisters, R., Lane, D. A., Nieuwlaat, R., de Vos, C. B., Crijns, H. J., & Lip, G. Y. (2010). A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest, 138, 1093–1100.PubMedCrossRefGoogle Scholar
  9. 9.
    Gage, B. F., Yan, Y., Milligan, P. E., Waterman, A. D., Culverhouse, R., & Rich, M. W. (2006). Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). American Heart Journal, 151, 713–719.PubMedCrossRefGoogle Scholar
  10. 10.
    Fang, M., Go, A., Chang, Y., Borowsky, L. H., Pmernacki, N. K., Udaltsova, N., et al. (2010). Abstract 16443: Development of a new risk stratification scheme to predict warfarin-associated hemorrhage: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. Circulation, 122, A16443.Google Scholar
  11. 11.
    Moons, K. G., Royston, P., Vergouwe, Y., Grobbee, D. E., & Altman, D. G. (2009). Prognosis and prognostic research: what, why, and how? BMJ, 338, b375.PubMedCrossRefGoogle Scholar
  12. 12.
    Hemingway, H., Croft, P., Perel, P., Hayden, J. A., Abrams, K., Timmis, A., et al. (2013). Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes. BMJ, 346, e5595.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Whiting, P., Rutjes, A. W., Reitsma, J. B., Bossuyt, P. M., & Kleijnen, J. (2003). The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Medical Research Methodology, 3, 25.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Glas, A. S., Lijmer, J. G., Prins, M. H., Bonsel, G. J., & Bossuyt, P. M. (2003). The diagnostic odds ratio: a single indicator of test performance. Journal of Clinical Epidemiology, 56, 1129–1135.PubMedCrossRefGoogle Scholar
  15. 15.
    Oosterhuis, W. P., Niessen, R. W., & Bossuyt, P. M. (2000). The science of systematic reviewing studies of diagnostic tests. Clinical Chemistry and Laboratory Medicine, 38, 577–588.PubMedCrossRefGoogle Scholar
  16. 16.
    Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21, 1539–1558.PubMedCrossRefGoogle Scholar
  17. 17.
    Olesen, J. B., Lip, G. Y., Hansen, P. R., Lindhardsen, J., Ahlehoff, O., Andersson, C., et al. (2011). Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort. Journal of Thrombosis and Haemostasis, 9, 1460–1467.PubMedCrossRefGoogle Scholar
  18. 18.
    Friberg, L., Rosenqvist, M., & Lip, G. Y. (2012). Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. European Heart Journal, 33, 1500–1510.PubMedCrossRefGoogle Scholar
  19. 19.
    Apostolakis, S., Lane, D. A., Guo, Y., Buller, H., & Lip, G. Y. (2012). Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. Journal of the American College of Cardiology, 60, 861–867.PubMedCrossRefGoogle Scholar
  20. 20.
    Apostolakis, S., Lane, D. A., Guo, Y., Buller, H., & Lip, G. Y. (2013). Performance of the HEMORR2HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in nonwarfarin anticoagulated atrial fibrillation patients. Journal of the American College of Cardiology, 61, 386–387.PubMedCrossRefGoogle Scholar
  21. 21.
    Roldán, V., Marín, F., Fernández, H., Manzano-Fernandez, S., Gallego, P., Valdés, M., et al. (2013). Predictive value of the HAS-BLED and ATRIA bleeding scores for the risk of serious bleeding in a "real-world" population with atrial fibrillation receiving anticoagulant therapy. Chest, 143, 179–184.PubMedCrossRefGoogle Scholar
  22. 22.
    Seet, R. C., Rabinstein, A. A., Christianson, T. J., Petty, G. W., & Brown, R. D., Jr. (2013). Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study. Journal of Stroke and Cerebrovascular Diseases, 22, 561–569.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Schulman, S., Kearon, C., & Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. (2005). Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Journal of Thrombosis and Haemostasis, 3, 692–694.PubMedCrossRefGoogle Scholar
  24. 24.
    Hamon, M., Filippi-Codaccioni, E., Riddell, J. W., & Lepage, O. (2007). Prognostic impact of major bleeding in patients with acute coronary syndromes. A systematic review and meta-analysis. EuroIntervention, 3, 400–408.PubMedCrossRefGoogle Scholar
  25. 25.
    Ruiz-Nodar, J. M., Marín, F., Roldán, V., Valencia, J., Manzano-Fernández, S., Caballero, L., et al. (2012). Should we recommend oral anticoagulation therapy in patients with atrial fibrillation undergoing coronary artery stenting with a high HAS-BLED bleeding risk score? Circulation. Cardiovascular Interventions, 5, 459–466.PubMedCrossRefGoogle Scholar
  26. 26.
    Lip, G. Y., Banerjee, A., Lagrenade, I., Lane, D. A., Taillandier, S., & Fauchier, L. (2012). Assessing the risk of bleeding in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation project. Circulation. Arrhythmia and Electrophysiology, 5, 941–948.PubMedCrossRefGoogle Scholar
  27. 27.
    Smith, J. G., Wieloch, M., Koul, S., Braun, O. Ö., Lumsden, J., Rydell, E., et al. (2012). Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. EuroIntervention, 8, 672–678.PubMedCrossRefGoogle Scholar
  28. 28.
    Omran, H., Bauersachs, R., Rübenacker, S., Goss, F., & Hammerstingl, C. (2012). The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thrombosis & Haemostasis, 108, 65–73.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Daniel Caldeira
    • 1
    • 2
    • 6
    Email author
  • João Costa
    • 1
    • 2
    • 3
    • 4
  • Ricardo M. Fernandes
    • 1
    • 2
  • Fausto J. Pinto
    • 5
  • Joaquim J. Ferreira
    • 1
    • 2
  1. 1.Clinical Pharmacology UnitInstituto de Medicina MolecularLisbonPortugal
  2. 2.Laboratory of Clinical Pharmacology and Therapeutics, Faculty of MedicineUniversity of LisbonLisbonPortugal
  3. 3.Portuguese Collaborating Centre of the Cochrane Iberoamerican Network, Faculty of MedicineUniversity of LisbonLisbonPortugal
  4. 4.Evidence-Based Medicine Centre, Faculty of MedicineUniversity of LisbonLisbonPortugal
  5. 5.Cardiology Department, CCUL, CAMLUniversity of LisbonLisbonPortugal
  6. 6.Cardiology DepartmentHospital Garcia de OrtaAlmadaPortugal

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