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Original research
Novel bleeding prediction model in atrial fibrillation patients on new oral anticoagulants
  1. Ofra Barnett-Griness1,
  2. Nili Stein1,
  3. Antonio Kotler2,
  4. Walid Saliba1,3,
  5. Naomi Gronich1,3
  1. 1Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel
  2. 2Hematology, Lady Davis Carmel Medical Center, Haifa, Israel
  3. 3The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
  1. Correspondence to Dr Naomi Gronich, Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; gronichn{at}


Objective Clinical models such as the HAS-BLED (standing for Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage) were developed to predict risk of major bleeding on vitamin K antagonists/antiplatelet therapy. We aimed to develop a model that will improve the ability to predict major bleeding events in patients with non-valvular atrial fibrillation (AF) treated with new oral anticoagulants (NOACs).

Methods Clalit Health Services is the largest of four integrated healthcare organisations in Israel, which insures 4.7 million patients (53% of the population). We identified in Clalit Health Services all patients with AF, new users of an NOAC (2013–2017), and followed them until first occurrence of a major bleeding event, death, switch to another oral anticoagulant, 30 days after discontinuation of NOAC or end of follow-up (31 December 2019). Importance of the candidate model variables was estimated by inclusion frequencies across forward selection algorithm applied to 50 bootstrap samples. Then, backward selection algorithm using the modified Bayesian Information Criterion for competing risks was applied to select predictors for the final model.

Results 47 623 patients with AF prescribed NOAC were studied. 28 055 patients with AF, initiators of apixaban (mean age 78.7, SD 9.0), were included in the first phase and had 662 major bleeding events. Nine variables were selected for inclusion in a final points-based risk-scoring system: male sex, anaemia, thrombocytopaenia (<99×103/µL), concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low estimated glomerular filtration rate, with apparent area-under-curve (AUC) of 0.6546. Applicability of the model was then shown for 14 118 and 5450 patients with AF, initiators of dabigatran and rivaroxaban, where the score achieved c indices of 0.62 and 0.61, respectively.

Conclusions We present a novel and simple risk score for prediction of major bleeding in patients with non-valvular AF treated with NOACs. Validation in additional cohorts is warranted.

  • atrial fibrillation

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • WS and NG contributed equally.

  • Contributors OB-G and NS performed the analysis; OB-G, AK, WS and NG designed the research study; OB-G and NG wrote the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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