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Thromb Haemost 2021; 121(11): 1512-1522
DOI: 10.1055/s-0041-1726345
Stroke, Systemic or Venous Thromboembolism

Comparison of Bleeding Risk Scores in Elderly Patients Receiving Extended Anticoagulation with Vitamin K Antagonists for Venous Thromboembolism

Andrea N. Frei
1   Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
,
Odile Stalder
2   CTU Bern, University of Bern, Bern, Switzerland
,
Andreas Limacher
2   CTU Bern, University of Bern, Bern, Switzerland
,
Marie Méan
3   Department of General Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Christine Baumgartner
1   Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
,
Nicolas Rodondi
1   Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
4   Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
,
Drahomir Aujesky
1   Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
› Author Affiliations Funding This work was supported by the Swiss National Science Foundation (Grant no. 33CSO-122659/139470).
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Abstract

Background In elderly patients with venous thromboembolism (VTE), the decision to extend anticoagulation beyond 3 months must be weighed against the bleeding risk. We compared the predictive performance of 10 clinical bleeding scores (VTE-BLEED, Seiler, Kuijer, Kearon, RIETE, ACCP, OBRI, HEMORR2HAGES, HAS-BLED, ATRIA) in elderly patients receiving extended anticoagulation for VTE.

Methods In a multicenter Swiss cohort study, we analyzed 743 patients aged ≥65 years who received extended treatment with vitamin K antagonists after VTE. The outcomes were the time to a first major and clinically relevant bleeding. For each score, we classified patients into two bleeding risk categories (low/moderate vs. high). We calculated likelihood ratios and the area under the receiver operating characteristic (ROC) curve for each score.

Results Over a median anticoagulation duration of 10.1 months, 45 patients (6.1%) had a first major and 127 (17.1%) a clinically relevant bleeding. The positive likelihood ratios for predicting major bleeding ranged from 0.69 (OBRI) to 2.56 (Seiler) and from 1.07 (ACCP) to 2.36 (Seiler) for clinically relevant bleeding. The areas under the ROC curves were poor to fair and varied between 0.47 (OBRI) and 0.70 (Seiler) for major and between 0.52 (OBRI) and 0.67 (HEMORR2HAGES) for clinically relevant bleeding.

Conclusion The predictive performance of most clinical bleeding risk scores does not appear to be sufficiently high to identify elderly patients with VTE who are at high risk of bleeding and who may therefore not be suitable candidates for extended anticoagulation.

Keywords

anticoagulants - bleeding - elderly - risk scores - venous thromboembolism

Author Contributions

A.N. Frei and D. Aujesky were responsible for study concept and design. O. Stalder and A. Limacher performed the statistical analyses. A.N. Frei and D. Aujesky wrote the manuscript. O. Stalder, A. Limacher, M. Méan, C. Baumgartner, and N. Rodondi revised the manuscript. M. Méan and D. Aujesky collected the data and obtained funding from the Swiss National Science Foundation.


Supplementary Material



Publication History

Received: 16 November 2020

Accepted: 09 February 2021

Article published online:
30 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedSearch in Google Scholar
  • 2 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139 (11) 893-900
    CrossrefPubMedSearch in Google Scholar
  • 3 Spencer FA, Gore JM, Lessard D. et al. Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost 2008; 100 (05) 780-788
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Di Minno MN, Ambrosino P, Dentali F. Safety of warfarin in “high-risk” populations: a meta-analysis of randomized and controlled trials. Thromb Res 2017; 150: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 5 Klok FA, Kooiman J, Huisman MV, Konstantinides S, Lankeit M. Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review. Eur Respir J 2015; 45 (01) 201-210
    CrossrefPubMedSearch in Google Scholar
  • 6 Klok FA, Hösel V, Clemens A. et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J 2016; 48 (05) 1369-1376
    CrossrefPubMedSearch in Google Scholar
  • 7 Seiler E, Limacher A, Mean M. et al. Derivation and validation of a novel bleeding risk score for elderly patients with venous thromboembolism on extended anticoagulation. Thromb Haemost 2017; 117 (10) 1930-1936
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Kuijer PM, Hutten BA, Prins MH, Büller HR. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159 (05) 457-460
    CrossrefPubMedSearch in Google Scholar
  • 9 Kearon C, Ginsberg JS, Kovacs MJ. et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349 (07) 631-639
    CrossrefPubMedSearch in Google Scholar
  • 10 Ruíz-Giménez N, Suárez C, González R. et al; RIETE Investigators. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100 (01) 26-31
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med 1989; 87 (02) 144-152
    CrossrefPubMedSearch in Google Scholar
  • 12 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. 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 2010; 138 (05) 1093-1100
    CrossrefPubMedSearch in Google Scholar
  • 13 Gage BF, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151 (03) 713-719
    CrossrefPubMedSearch in Google Scholar
  • 14 Fang MC, Go AS, Chang Y. et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58 (04) 395-401
    CrossrefPubMedSearch in Google Scholar
  • 15 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105 (02) 91-99
    CrossrefPubMedSearch in Google Scholar
  • 16 Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med 2013; 126 (09) 832.e13-832.e21
    CrossrefPubMedSearch in Google Scholar
  • 17 Méan M, Righini M, Jaeger K. et al. The Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+): rationale and methodology. J Thromb Thrombolysis 2013; 36 (04) 475-483
    CrossrefPubMedSearch in Google Scholar
  • 18 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e419S-e496S
    CrossrefPubMedSearch in Google Scholar
  • 19 Besarab A, Bolton WK, Browne JK. et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339 (09) 584-590
    CrossrefPubMedSearch in Google Scholar
  • 20 Kämpfen P, Méan M, Limacher A. et al. Risk of falls and bleeding in elderly patients with acute venous thromboembolism. J Intern Med 2014; 276 (04) 378-386
    CrossrefPubMedSearch in Google Scholar
  • 21 Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69 (03) 236-239
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedSearch in Google Scholar
  • 23 Scherz N, Méan M, Limacher A. et al. Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism. J Thromb Haemost 2013; 11 (03) 435-443
    CrossrefPubMedSearch in Google Scholar
  • 24 Jakobsson C, Jiménez D, Gómez V, Zamarro C, Méan M, Aujesky D. Validation of a clinical algorithm to identify low-risk patients with pulmonary embolism. J Thromb Haemost 2010; 8 (06) 1242-1247
    CrossrefPubMedSearch in Google Scholar
  • 25 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
  • 26 Jaeschke R, Guyatt GH, Sackett DL. Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA 1994; 271 (09) 703-707
    CrossrefPubMedSearch in Google Scholar
  • 27 Poli D, Antonucci E, Testa S, Cosmi B, Palareti G, Ageno W. FCSA Italian Federation of Anticoagulation Clinics. The predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study. J Thromb Haemost 2013; 11 (06) 1053-1058
    CrossrefPubMedSearch in Google Scholar
  • 28 Donzé J, Rodondi N, Waeber G, Monney P, Cornuz J, Aujesky D. Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study. Am J Med 2012; 125 (11) 1095-1102
    CrossrefPubMedSearch in Google Scholar
  • 29 Jaspers Focks J, van Vugt SP, Albers-Akkers MT. et al. Low performance of bleeding risk models in the very elderly with atrial fibrillation using vitamin K antagonists. J Thromb Haemost 2016; 14 (09) 1715-1724
    CrossrefPubMedSearch in Google Scholar
  • 30 Geldhof V, Vandenbriele C, Verhamme P, Vanassche T. Venous thromboembolism in the elderly: efficacy and safety of non-VKA oral anticoagulants. Thromb J 2014; 12: 21
    CrossrefPubMedSearch in Google Scholar
  • 31 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (08) 699-708
    CrossrefPubMedSearch in Google Scholar
  • 32 Weitz JI, Lensing AWA, Prins MH. et al; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 2017; 376 (13) 1211-1222
    CrossrefPubMedSearch in Google Scholar
  • 33 Riva N, Bellesini M, Di Minno MN. et al. Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study. Thromb Haemost 2014; 112 (03) 511-521
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Mai V, Guay CA, Perreault L. et al. Extended anticoagulation for VTE: a systematic review and meta-analysis. Chest 2019; 155 (06) 1199-1216
    CrossrefPubMedSearch in Google Scholar
  • 35 Aujesky D, Obrosky DS, Stone RA. et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172 (08) 1041-1046
    CrossrefPubMedSearch in Google Scholar
  • 36 Fine MJ, Auble TE, Yealy DM. et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336 (04) 243-250
    CrossrefPubMedSearch in Google Scholar