10.4081/btvb.2023.97
Not available
application/pdf
2785-5309
97
3
en
Paolo Prandoni
https://creativecommons.org/licenses/by-nc/4.0
Bleeding, Thrombosis and Vascular Biology
risk assessment tool
Personalized bleeding risk assessment for atrial fibrillation patients on direct oral anticoagulants: the DOAC score
Text.Serial.Journal
https://www.btvb.org/btvb
2
Invited Editorials
2023-10-11
2023-09-26
2023-07-31
2023-11-15
Bleed Thromb Vascul Biol
Paolo Prandoni
2023/10/11
10.4081/btvb.2023.97
Arianna Foundation on Anticoagulation, Bologna
2785-5309
3
risk assessment tool
en
Connolly SJ, Healey JS, Belley-Cote EP, et al. Oral Anticoagulation use and left atrial appendage occlusion in LAAOS III. Circulation 2023 Sep 21. [Epub ahead of print].
Personalized bleeding risk assessment for atrial fibrillation patients on direct oral anticoagulants: the DOAC score
https://www.btvb.org/btvb/article/download/97/84
2
                                                                                                           INVITED EDITORIAL

Personalized bleeding risk assessment for atrial fibrillation patients
on direct oral anticoagulants: the DOAC score
Paolo Prandoni

Arianna Foundation on Anticoagulation, Bologna, Italy




                                                                            sessment tool designed to personalize bleeding risk estimates for
Introduction                                                                AF patients on DOACs.2
    Atrial fibrillation (AF) is a common cardiac arrhythmia that
significantly increases the risk of stroke and systemic embolism.
To mitigate these risks, individuals with AF are often prescribed           Developing the DOAC Score
anticoagulant medications, such as warfarin or direct-acting oral
                                                                                 The study, conducted across 44 countries and involving 951




                                                                                                       ly
anticoagulants (DOACs). However, the use of anticoagulants
                                                                            centers, drew upon a diverse cohort of AF patients taking dabiga-
comes with its own set of concerns, particularly the risk of bleed-




                                                                                               on
                                                                            tran 150 mg twice daily.3 The researchers developed a risk score
ing. Current clinical tools for assessing bleeding risk in AF pa-
                                                                            by analyzing various patient-specific factors using a Cox propor-
tients have been primarily developed for those treated with
                                                                            tional hazards model. The resultant risk prediction model under-
warfarin and have shown limited performance when applied to




                                                                                         e
                                                                            went rigorous internal validation through bootstrapping techniques.
individuals on DOAC therapy.1 In response to this gap, a recent
                                                                            The DOAC Score was then further refined in the GARFIELD-AF
study has introduced the DOAC Score, a novel clinical risk as-
                                                                                  us
                                                                            registry, which included patients taking a range of DOACs, includ-
                                                                            ing dabigatran, edoxaban, rivaroxaban, and apixaban.4 Finally, to
                                                                            al
                                                                            determine generalizability in external cohorts and among individ-
                                                                            uals on different DOACs, the risk prediction model was validated
                                                                  ci

  Correspondence: Paolo Prandoni, the Arianna Foundation on An-             in the COMBINE-AF pooled clinical trial cohort,5 and in the Que-
  ticoagulation, Via P. Fabbri 1/3, 40138 Bologna, Italy.                   bec Régie de l’Assurance Maladie du Québec and Med-Echo Ad-
                                                                er


  Tel.: +39.340.2808202.                                                    ministrative Databases (RAMQ) administrative database.6
  E-mail: prandonip@gmail.com
                                                               m




  Citation: Prandoni P. Personalized bleeding risk assessment for
                                                                            Key findings
                                                    om




  atrial fibrillation patients on direct oral anticoagulants: the DOAC
  score. Bleeding, Thrombosis, and Vascular Biology 2023;2:97.
                                                                                 One of the primary outcomes assessed in this study was the
  Key words: atrial fibrillation, direct oral anticoagulants, hemor-        incidence of major bleeding events among AF patients, defined
                                             -c




  rhagic risk, risk assessment tool.                                        according to the classification of the International Society on
                                    on




                                                                            Thrombosis and Haemostasis.7 Of the 5684 patients in the RE-LY
  Conflict of interest: the author declares no potential conflict of in-
                                                                            trial, 6.8% experienced a major bleeding event over a median fol-
  terest.
                                                                            low-up period of 1.74 years. The DOAC Score proved to be a re-
                              N




  Funding: none.                                                            liable predictor of bleeding risk, with an optimism-corrected C
                                                                            statistic of 0.73 after internal validation. Calibration plots demon-
  Received: 26 September 2023.                                              strated excellent goodness-of-fit (p=0.57), indicating that the
  Accepted: 29 September 2023.                                              model accurately estimated bleeding risk.
                                                                                 The DOAC Score assigns points based on various patient
  Publisher’s note: all claims expressed in this article are solely those
                                                                            characteristics, including age, creatinine clearance/glomerular fil-
  of the authors and do not necessarily represent those of their affili-
                                                                            tration rate, underweight status, history of stroke/transient is-
  ated organizations, or those of the publisher, the editors and the re-
  viewers. Any product that may be evaluated in this article or claim       chemic attack/embolism, diabetes, hypertension, antiplatelet use,
  that may be made by its manufacturer is not guaranteed or endorsed        nonsteroidal anti-inflammatory use, liver disease, and bleeding
  by the publisher.                                                         history (Table 1). Importantly, each additional point on the DOAC
                                                                            Score was associated with a substantial 48.7% increase in the risk
  ©
   Copyright: the Author(s), 2023                                           of major bleeding. This underscores the tool’s effectiveness in
  Licensee PAGEPress, Italy                                                 stratifying patients based on their expected bleeding risk. The risk
  Bleeding, Thrombosis and Vascular Biology 2023; 2:97                      of bleeding is defined as being very low in case of a score ranging
  doi:10.4081/btvb.2023.97
                                                                            from 0 to 3, low 4 or 5, moderate 6 or 7, high 8 or 9, very high if
  This work is licensed under a Creative Commons Attribution-               the score is ≥10. The assessment refers to the first year of an-
  NonCommercial 4.0 International License (CC BY-NC 4.0).                   tithrombotic therapy, so it does not apply to subsequent periods;
                                                                            conceptually, the score should be recalculated at the end of each
                                                                            year of treatment.


                                              Bleeding, Thrombosis and Vascular Biology 2023; 2:97
             Personalized bleeding risk assessment for atrial fibrillation patients on direct oral anticoagulants: the DOAC score              47



                                                                               tool, ongoing evaluation and refinement will be necessary to en-
Comparison with existing tools                                                 sure its continued accuracy and relevance. Future research
                                                                               should also explore the implementation of the DOAC Score in
    One of the notable aspects of the study was the comparison
                                                                               real-world clinical practice to assess its impact on patient care
of the DOAC Score with the widely used HAS-BLED score.8,9
                                                                               and outcomes.
The DOAC Score consistently outperformed HAS-BLED in all
phases of the study. In the RE-LY trial, the DOAC Score had a
higher C statistic (0.73 versus 0.60) and demonstrated superior
predictive performance. Similar results were observed in the
                                                                               Conclusions
GARFIELD-AF registry (C statistic, 0.71 versus 0.66), COM-                         In conclusion, the development and validation of the DOAC
BINE-AF cohort (C statistic, 0.67 versus 0.63), and the RAMQ                   Score represent a significant step forward in the management of
administrative database (C statistic, 0.65 versus 0.58). These                 AF. This innovative tool offers a personalized approach to as-
findings suggest that the DOAC Score is not only more accurate                 sessing bleeding risk in AF patients on DOAC therapy, outper-
but also more robust across different cohorts and DOAC types.                  forming existing scoring systems and providing clinicians with
                                                                               a valuable resource for making treatment decisions.
                                                                                   As we move toward an era of precision medicine, the DOAC
Implications and future directions                                             Score exemplifies the potential of data-driven healthcare to im-
                                                                               prove patient safety and the quality of care provided to individ-




                                                                                                  ly
    The introduction of the DOAC Score represents a signifi-                   uals with AF.




                                                                                          on
cant advancement in personalized medicine for AF patients. By
providing a more accurate and tailored assessment of bleeding
risk, this tool enables healthcare providers to make more in-                  References



                                                                                    e
formed decisions when prescribing anticoagulant therapy. This,
in turn, can help optimize treatment strategies, minimize the                   1. Klok FA, Huisman MV. How I assess and manage the risk of
risk of bleeding complications, and improve patient outcomes.
In addition, the DOAC score has the potential to help physi-
                                                                              us   bleeding in patients treated for venous thromboembolism.
                                                                                   Blood 2020;135:724-34.
cians choose the most appropriate dosages of DOACs, and                         2. Aggarwal R, Ruff CT, Virdone S, et al. Development and val-
                                                                              al
identify candidates for left atrial appendage occlusion, which                     idation of the DOAC score: a novel bleeding risk prediction
                                                          ci

increasingly qualifies as a suitable tool for subjects at high he-                 tool for patients with atrial fibrillation on direct-acting oral
morrhagic risk.10                                                                  anticoagulants. Circulation 2023;148:936-46.
                                                        er


    The study’s broad international scope and validation across                 3. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus
diverse patient populations lend credibility to the DOAC Score’s                   warfarin in patients with atrial fibrillation. N Engl J Med
                                                       m




generalizability. However, as with any clinical risk assessment                    2009;361:1139-51.
                                                                                4. Kakkar AK, Mueller I, Bassand JP, et al. International longi-
                                           om




                                                                                   tudinal registry of patients with atrial fibrillation at risk of
                                                                                   stroke: Global Anticoagulant Registry in the FIELD
Table 1. DOAC score.
                                                                                   (GARFIELD). Am Heart J. 2012;163:13-9.
                                    -c




Clinical risk prediction tools                                 Points           5. Carnicelli AP, Hong H, Giugliano RP, et al. Individual patient
                           on




                                                                                   data from the pivotal randomized controlled trials of non-vi-
Age, years
                                                                                   tamin K antagonist oral anticoagulants in patients with atrial
 65-69                                                            2
                                                                                   fibrillation (COMBINE AF): design and rationale from the
                     N




 70-74                                                            3
 75-79                                                            4                COMBINE AF investigators. Am Heart J 2021;233:48-58.
 ≥80                                                              5             6. Qazi JZ, Schnitzer ME, Côté R, et al. Predicting major bleed-
Creatinine clearance, mL/min                                                       ing among hospitalized patients using oral anticoagulants for
 30-60                                                            1                atrial fibrillation after discharge. PLoS One 2021;16:
                                                                                   e0246691.
 <30                                                              2
                                                                                7. Schulman S, Kearon. Definition of major bleeding in clinical
Underweight (body mass index <18.5 kg/m2)                         1
                                                                                   investigations of antihemostatic medicinal products in non-
Stroke/transient ischemic attack/embolism history                 1                surgical patients. J Thromb Haemost 2005;3:692-4.
Blood hypertension                                                1             8. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly
Diabetes mellitus                                                 1                score (HAS-BLED) to assess 1-year risk of major bleeding
Antiplatelet use                                                                   in patients with atrial fibrillation: the Euro Heart Survey.
 Aspirin                                                          2                Chest 2010;138:1093-100.
 Dual-antiplatelet                                                3             9. Borre ED, Goode A, Raitz G, et al. Predicting thromboem-
Nonsteroidal anti-inflammatory use                                1                bolic and bleeding event risk in patients with non-valvular
                                                                                   atrial fibrillation: a systematic review. Thromb Haemost
Bleeding history                                                  3
                                                                                   2018;118:2171-87.
Liver disease*                                                    2
                                                                               10. Connolly SJ, Healey JS, Belley-Cote EP, et al. Oral Antico-
*Defined as: aspartate aminotransferase, alanine aminotransferase, alkaline
phosphatase ≥3X upper limit of normal, alkaline phosphatase ≥2X upper limit
                                                                                   agulation use and left atrial appendage occlusion in LAAOS
of normal, or liver cirrhosis.                                                     III. Circulation 2023 Sep 21. [Epub ahead of print].


                                               Bleeding, Thrombosis and Vascular Biology 2023; 2:97
