Download PDF
Thromb Haemost 2021; 121(08): 1107-1114
DOI: 10.1055/a-1333-4448
Stroke, Systemic or Venous Thromboembolism

Stroke and Thromboembolism in Warfarin-Treated Patients with Atrial Fibrillation: Comparing the CHA2DS2-VASc and GARFIELD-AF Risk Scores

Marco Proietti    *
1   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
2   Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
3   Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
,
José Miguel Rivera-Caravaca  ‡   *
4   Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBER-CV, Murcia, Spain
,
María Asunción Esteve-Pastor 
4   Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBER-CV, Murcia, Spain
,
Francísco Marín
4   Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBER-CV, Murcia, Spain
,
Gregory Y. H. Lip    **
1   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
5   Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
› Author Affiliations Funding No funding has been received in the preparation of this manuscript. Astra Zeneca provided datasets for the analysis. Astra Zeneca was never involved in any stage of manuscript drafting and preparation.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Background Evaluation of thromboembolic risk is essential in anticoagulated atrial fibrillation (AF) patients. The CHA2DS2-VASc score is largely validated and recommended by most guidelines. The GARFIELD-AF Stroke score has been proposed as an alternative risk score.

Methods We analyzed warfarin-treated patients from SPORTIF III and V studies. Any thromboembolic event (TE) was an adjudicated study outcome. We compared the two scores' capacity in predicting any TE occurrence.

Results A total of 3,665 patients (median [interquartile range] age: 72 [66–77] years; 30.5% female) were included in this analysis. After a mean (standard deviation) follow-up of 566.3 (142.5) days, 148 (4.03%) TEs were recorded. Both continuous CHA2DS2-VASc and GARFIELD-AF were associated with TE (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.22–1.53 and HR: 2.43, 95% CI: 1.72–3.42), with modest predictive ability (c-indexes: 0.63, 95% CI: 0.59–0.68 and 0.61, 95% CI: 0.56–0.66, respectively), with no differences. CHA2DS2-VASc quartiles showed an increasing cumulative risk, while in GARFIELD-AF only the highest quartile (Q4) demonstrated an increased TE risk. On multivariate Cox regression analysis, CHA2DS2-VASc quartiles were associated with increasing risk of TE, whereas for GARFIELD-AF only Q4 showed an association with TE. Discrimination analysis showed that GARFIELD-AF quartiles were associated with a 48.7% reduction in discriminatory ability. Using decision curve analysis, CHA2DS2-VASc was associated with improved clinical usefulness and net clinical benefit, compared with GARFIELD-AF.

Conclusion In a warfarin-treated trial cohort of AF patients, both CHA2DS2-VASc and GARFIELD-AF Stroke scores were associated with adjudicated TE events, with modest predictive capacity. The simpler CHA2DS2-VASc score improved discriminatory capacity compared with the more complex GARFIELD-AF score, demonstrating improved clinical usefulness and net clinical benefit.

Keywords

atrial fibrillation - risk scores - thromboembolic events

* Both authors equally contributed to the manuscript.


** The editorial process for this paper article was fully handled by Prof. Christian Weber, Editor-in-Chief.


Supplementary Material



Publication History

Received: 23 September 2020

Accepted: 04 December 2020

Accepted Manuscript online:
09 December 2020

Article published online:
26 January 2021

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Lip G, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial fibrillation: past, present and future. Comparing the guidelines and practical decision-making. Thromb Haemost 2017; 117 (07) 1230-1239
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Proietti M, Lane DA, Boriani G. et al. Stroke prevention, evaluation of bleeding risk, and anticoagulant treatment management in atrial fibrillation contemporary international guidelines. Can J Cardiol 2019; 35 (05) 619-633
    CrossrefPubMedSearch in Google Scholar
  • 3 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
    CrossrefPubMedSearch in Google Scholar
  • 4 Lip GYH, Banerjee A, Boriani G. et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018; 154 (05) 1121-1201
    CrossrefPubMedSearch in Google Scholar
  • 5 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020;
    CrossrefPubMedSearch in Google Scholar
  • 6 Fanola CL, Giugliano RP, Ruff CT. et al. A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial. Eur Heart J 2017; 38 (12) 888-896
    PubMedSearch in Google Scholar
  • 7 Oldgren J, Hijazi Z, Lindbäck J. et al; RE-LY and ARISTOTLE Investigators. Performance and validation of a novel biomarker-based stroke risk score for atrial fibrillation. Circulation 2016; 134 (22) 1697-1707
    CrossrefPubMedSearch in Google Scholar
  • 8 Fox KAA, Lucas JE, Pieper KS. et al; GARFIELD-AF Investigators. Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation. BMJ Open 2017; 7 (12) e017157
    CrossrefPubMedSearch in Google Scholar
  • 9 Borre ED, Goode A, Raitz G. et al. Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review. Thromb Haemost 2018; 118 (12) 2171-2187
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Proietti M, Mujovic N, Potpara TS. Optimizing stroke and bleeding risk assessment in patients with atrial fibrillation: a balance of evidence, practicality and precision. Thromb Haemost 2018; 118 (12) 2014-2017
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Kakkar AK, Mueller I, Bassand JP. et al. International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD). Am Hear J 2012; 163 (01) 13.e1-19.e1
    CrossrefPubMedSearch in Google Scholar
  • 12 Dalgaard F, Pieper K, Verheugt F. et al. GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study. BMJ Open 2019; 9 (11) e033283
    CrossrefPubMedSearch in Google Scholar
  • 13 Halperin JL. Executive Steering Committee, SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003; 146 (03) 431-438
    CrossrefPubMedSearch in Google Scholar
  • 14 Olsson SB. Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362 (9397): 1691-1698
    CrossrefPubMedSearch in Google Scholar
  • 15 Albers GW, Diener H-C, Frison L. et al; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005; 293 (06) 690-698
    CrossrefPubMedSearch in Google Scholar
  • 16 Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
    CrossrefPubMedSearch in Google Scholar
  • 17 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
    CrossrefPubMedSearch in Google Scholar
  • 18 Pencina MJ, D'Agostino Sr RB, D'Agostino Jr RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27 (02) 157-172
    CrossrefPubMedSearch in Google Scholar
  • 19 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26 (06) 565-574
    CrossrefPubMedSearch in Google Scholar
  • 20 Vickers AJ, Cronin AM, Elkin EB, Gonen M. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 2008; 8: 53
    CrossrefPubMedSearch in Google Scholar
  • 21 Zhu WG, Xiong QM, Hong K. Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation. Texas Hear Inst J 2015; 42: 6-15
    CrossrefPubMedSearch in Google Scholar
  • 22 Olesen JB, Lip GYH, Hansen ML. et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011; 342: d124
    CrossrefPubMedSearch in Google Scholar
  • 23 Chao TF, Liu CJ, Tuan TC. et al. Comparisons of CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in atrial fibrillation: Which scoring system should be used for Asians?. Hear Rhythm 2016; 13: 46-53
    CrossrefPubMedSearch in Google Scholar
  • 24 Proietti M, Farcomeni A, Romiti GF. et al. Association between clinical risk scores and mortality in atrial fibrillation: systematic review and network meta-regression of 669,000 patients. Eur J Prev Cardiol 2020; 27 (06) 633-644
    CrossrefPubMedSearch in Google Scholar
  • 25 Bassand J-P, Accetta G, Camm AJ. et al; GARFIELD-AF Investigators. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 2016; 37 (38) 2882-2889
    CrossrefPubMedSearch in Google Scholar
  • 26 Camm AJ, Accetta G, Ambrosio G. et al; GARFIELD-AF Investigators. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart 2017; 103 (04) 307-314
    CrossrefPubMedSearch in Google Scholar
  • 27 Camelo-Castillo A, Rivera-Caravaca JM, Marín F, Vicente V, Lip GYH, Roldán V. Predicting adverse events beyond stroke and bleeding with the ABC-stroke and ABC-bleeding scores in patients with atrial fibrillation: the Murcia AF Project. Thromb Haemost 2020; 120 (08) 1200-1207
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Esteve-Pastor MA, Roldán V, Rivera-Caravaca JM, Ramírez-Macías I, Lip GYH, Marín F. The use of biomarkers in clinical management guidelines: a critical appraisal. Thromb Haemost 2019; 119 (12) 1901-1919
    Thieme ConnectPubMedSearch in Google Scholar