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Predicting the risk for major bleeding in elderly patients with venous thromboembolism using the Charlson index. Findings from the RIETE

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Abstract

Old patients receiving anticoagulant therapy for venous thromboembolism (VTE) are at an increased risk for bleeding. We used data from the RIETE registry to assess the prognostic ability of the Comorbidity Charlson Index (CCI) to predict the risk for major bleeding in patients aged > 75 years receiving anticoagulation for VTE beyond the third month. We calculated the area under the receiver-operating characteristic curve (AUC), the category-based net reclassification index (NRI) and the net benefit (NB). We included 4303 patients with a median follow-up of 706 days (interquartile range [IQR] 462–1101). Of these, 147 (3%) developed major bleeding (27 died of bleeding). The AUC was 0.569 (95% CI 0.524–0.614). Patients with CCI ≤ 4 points were at a lower risk for adverse outcomes than those with CCI > 10 (major bleeding 0.81 (95% CI 0.53–1.19) vs. 2.21 (95% CI 1.18–3.79) per 100 patient-years; p < 0.05; all-cause death 1.9 (95% CI 1.45–2.44) vs. 15.67 (95% CI 12.63–19.22) per 100 patient-years; p < 0.05). A cut-off point of 4 points (CCI4) had a sensitivity of 82% (95% CI 75–89) and a specificity of 30% (95% CI 29–31) to predict major bleeding beyond the third month. CCI4 reclassification improved the NB of the RIETE bleeding score to predict bleeding beyond the third month (CCI4 NB 1.78% vs. RIETE NB 0.44%). Although the AUC of the CCI to predict major bleeding was modest, it could become an additional help to select patients aged > 75 years that obtain more benefit of extended anticoagulation, due to a lower risk for bleeding and better survival.

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Abbreviations

AMI:

Acute myocardial infarction

AUC:

Area under the receiver-operating characteristic curve

CCI:

Charlson comorbidity index

CI:

Confidence intervals

CrCl:

Creatinine clearance

DVT:

Deep vein thrombosis

INR:

International normalized ratio

IQR:

Interquartile range

NA:

Not applicable

NB:

Net benefit

NRI:

Net reclassification index

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OR:

Odds ratio

PE:

Pulmonary embolism

ROC:

Receiver-operating characteristic curve

VTE:

Venous thromboembolism

References

  1. Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease. Chest 149:315–352. https://doi.org/10.1016/j.chest.2015.11.026

    Article  PubMed  Google Scholar 

  2. Konstantinides SV, Meyer G, Becattini C et al (2019) 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): the Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of. Eur Respir J 54:1–61. https://doi.org/10.1183/13993003.01647-2019

    Article  Google Scholar 

  3. Spencer FA, Gore JM, Lessard D et al (2008) Venous thromboembolism in the elderly a community-based perspective. Thromb Haemost 100:780–788. https://doi.org/10.1160/TH08-04-0255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Leiss W, Méan M, Limacher A et al (2015) Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism. J Gen Intern Med 30:17–24. https://doi.org/10.1007/s11606-014-2993-8

    Article  PubMed  Google Scholar 

  5. López-Jiménez L, Montero M, González-Fajardo JA et al (2006) Venous thromboembolism in very elderly patients: findings from a prospective registry (RIETE). Haematologica 91:1046–1051

    PubMed  Google Scholar 

  6. Moustafa F, Giorgi Pierfranceschi M, Di Micco P et al (2017) Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism. Res Pract Thromb Haemost 1:172–179. https://doi.org/10.1002/rth2.12036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ruíz-Giménez N, Suárez C, González R et al (2008) Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 100:26–31. https://doi.org/10.1160/TH08-03-0193

    Article  CAS  PubMed  Google Scholar 

  8. Iñurrieta A, Pedrajas J, Núñez M et al (2018) Outcomes beyond the third month of anticoagulation in patients aged > 75 years with a first episode of unprovoked venous thromboembolism. TH Open 02:e428–e436. https://doi.org/10.1055/s-0038-1676359

    Article  Google Scholar 

  9. van Es N, Wells PS, Carrier M (2017) Bleeding risk in patients with unprovoked venous thromboembolism: a critical appraisal of clinical prediction scores. Thromb Res 152:52–60. https://doi.org/10.1016/j.thromres.2017.02.016

    Article  CAS  PubMed  Google Scholar 

  10. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383

    Article  CAS  Google Scholar 

  11. Polo Friz H, Corno V, Orenti A et al (2017) Comorbidity assessment as predictor of short and long-term mortality in elderly patients with hemodynamically stable acute pulmonary embolism. J Thromb Thrombolysis 44:316–323. https://doi.org/10.1007/s11239-017-1540-y

    Article  PubMed  Google Scholar 

  12. Ariza-Solé A, Guerrero C, Formiga F et al (2018) Global geriatric assessment and in-hospital bleeding risk in elderly patients with acute coronary syndromes: insights from the LONGEVO-SCA registry. Thromb Haemost 118:581–590. https://doi.org/10.1055/s-0038-1623532

    Article  PubMed  Google Scholar 

  13. Bikdeli B, Jimenez D, Hawkins M et al (2018) Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 118:214–224. https://doi.org/10.1160/th17-07-0511

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sakamoto J, Yamashita Y, Morimoto T et al (2019) Cancer-associated venous thromboembolism in the real world - from the Command VTE registry. Circ J 83:2271–2281. https://doi.org/10.1253/circj.CJ-19-0515

    Article  PubMed  Google Scholar 

  15. Pencina MJ, D’Agostino RB, D’Agostino RB, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172. https://doi.org/10.1002/sim.2929

    Article  PubMed  Google Scholar 

  16. Steyerberg EW, Van Calster B, Pencina MJ (2011) Medidas del rendimiento de modelos de predicción y marcadores pronósticos: evaluación de las predicciones y clasificaciones. Rev Esp Cardiol 64:788–794. https://doi.org/10.1016/j.recesp.2011.04.017

    Article  PubMed  Google Scholar 

  17. Steyerberg EW (2019) Clinical prediction models. Springer, Cham. https://doi.org/10.1007/978-3-030-16399-0

    Book  Google Scholar 

  18. Thomas LE, O’Brien EC, Piccini JP et al (2019) Application of net reclassification index to non-nested and point-based risk prediction models: a review. Eur Heart J 40:1880–1887. https://doi.org/10.1093/eurheartj/ehy345

    Article  PubMed  Google Scholar 

  19. Klok F, Barco S, Konstantinides S (2017) External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism. Thromb Haemost 117:1164–1170. https://doi.org/10.1160/TH16-10-0810

    Article  PubMed  Google Scholar 

  20. Riva N, Bellesini M, Di Minno MND et al (2014) Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism: a multicentre retrospective cohort study. Thromb Haemost 112:511–521. https://doi.org/10.1160/TH14-01-0081

    Article  CAS  PubMed  Google Scholar 

  21. Seiler E, Limacher A, Méan M et al (2017) Derivation and validation of a novel bleeding risk score for elderly patients with venous thromboembolism on extended anticoagulation. Thromb Haemost 117:1930–1936. https://doi.org/10.1160/th17-03-0162

    Article  Google Scholar 

  22. Toll DB, Janssen KJM, Vergouwe Y, Moons KGM (2008) Validation, updating and impact of clinical prediction rules: a review. J Clin Epidemiol 61:1085–1094. https://doi.org/10.1016/j.jclinepi.2008.04.008

    Article  CAS  PubMed  Google Scholar 

  23. Spencer FA, Gurwitz JH, Schulman S et al (2014) Venous thromboembolism in older adults: a community-based study. Am J Med 127:530–537. https://doi.org/10.1016/j.amjmed.2014.02.011

    Article  PubMed  Google Scholar 

  24. Carrier M, Le Gal G, Wells PS, Rodger MA (2010) Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 152:578–589. https://doi.org/10.7326/0003-4819-152-9-201005040-00008

    Article  PubMed  Google Scholar 

  25. Ng ACC, Chow V, Yong ASC et al (2013) Prognostic impact of the charlson comorbidity index on mortality following acute pulmonary embolism. Respiration 85:408–416. https://doi.org/10.1159/000342024

    Article  PubMed  Google Scholar 

  26. Partridge JSL, Harari D, Martin FC, Dhesi JK (2014) The impact of pre-operative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review. Anaesthesia 69:8–16. https://doi.org/10.1007/978-3-030-16399-0

    Article  PubMed  Google Scholar 

  27. Hoogendijk EO, Van Der Horst HE, Van De Ven PM et al (2016) Effectiveness of a Geriatric Care Model for frail older adults in primary care: results from a stepped wedge cluster randomized trial. Eur J Intern Med. https://doi.org/10.1016/j.ejim.2015.10.023

    Article  PubMed  Google Scholar 

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Acknowledgements

We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant. We also thank the RIETE Registry Coordinating Center, S&H Medical Science Service, for their quality control data, logistic and administrative support.

Coordinator of the RIETE Registry: Manuel Monreal. RIETE Steering Committee Members: Paolo Prandoni, Benjamin Brenner and Dominique Farge-Bancel. RIETE National Coordinators: Raquel Barba (Spain), Pierpaolo Di Micco (Italy), Laurent Bertoletti (France), Sebastian Schellong (Germany), Inna Tzoran (Israel), Abilio Bosevski (Portugal), Marijan Bosevski (R. Macedonia), Henri Bounameaux (Switzerland), Radovan Malý (Czech Republic), Peter Verhamme (Belgium), Joseph A. Caprini (USA), Hanh My Bui (Vietnam). RIETE Registry Coordinating Center: S & H Medical Science Service.

Members of the RIETE Group SPAIN: Adarraga MD, Agud M, Aibar MA, Alfonso J, Amado C, Arcelus JI, Ballaz A, Barba R, Barbagelata C, Barrón M, Barrón-Andrés B, Blanco-Molina A, Camon AM, Cañas I, Castro J, de Miguel J, del Toro J, Demelo-Rodríguez P, Díaz-Pedroche C, Díaz-Peromingo JA, Díez-Sierra J, Domínguez IM, Encabo M, Escribano JC, Fernández-Capitán C, Fidalgo MA, Flores K, Font C, Font L, Francisco I, Furest I, García MA, García-Bragado F, García-García M, García-Raso A, Gavín-Sebastián O, Gayol MC, Gil-Díaz A, Gómez V, Gómez-Cuervo C, González-Martínez J, Grau E, Gutiérrez J, Hernández-Blasco LM, Iglesias M, Jara-Palomares L, Jaras MJ, Jiménez D, Jiménez R, Joya MD, Jou I, Lima J, Llamas P, Lobo JL, López-Jiménez L, López-Meseguer M, López-Miguel P, López-Núñez JJ, López-Reyes R, López-Sáez JB, Lorente MA, Lorenzo A, Loring M, Madridano O, Maestre A, Marchena PJ, Martín-Martos F, Martínez-García MA, Mellado M, Moisés J, Monreal M, Morales MV, Muñoz-Blanco A, Nieto JA, Núñez MJ, Olivares MC, Olivera PE, Ortega-Michel C, Ortega-Recio MD, Osorio J, Otero R, Panadero-Macia M, Parra V, Pedrajas JM, Pellejero G, Pérez-Ductor C, Pérez-Jacoíste A, Pérez-Rus G, Peris ML, Porras JA, Portillo J, Riera-Mestre A, Rivas A, Rodríguez-Cobo A, Rodríguez-Matute C, Rosa V, Rubio CM, Ruiz-Giménez N, Ruiz-Sada P, Sahuquillo JC, Sala-Sainz MC, Salgueiro G, Sampériz A, Sánchez-Muñoz-Torrero JF, Sancho T, Soler S, Soto MJ, Suárez S, Suriñach JM, Torres MI, Tolosa C, Trujillo-Santos J, Uresandi F, Valle R, Vela JR, Vidal G, Villares P, ARGENTINA: Gutiérrez P, Vázquez FJ, BELGIUM: Vanassche T, Vandenbriele C, Verhamme P, CZECH REPUBLIC: Hirmerova J, Malý R, ECUADOR: Salgado E, FRANCE: Benzidia I, Bertoletti L, Bura-Riviere A, Debourdeau P, Courtois MC, Farge-Bancel D, Helfer H, Hij A, Mahé I, Moustafa F, GERMANY: Schellong S, ISRAEL: Braester A, Brenner B, Tzoran I, ITALY: Bilora F, Bortoluzzi C, Bucherini E, Ciammaichella M, Dentali F, Di Micco P, Grandone E, Imbalzano E, Maida R, Mastroiacovo D, Pace F, Parisi R, Pesavento R, Pinelli M, Pomero F, Prandoni P, Quintavalla R, Rocci A, Siniscalchi C, Tiraferri E, Tufano A, Visonà A, Vo Hong N, Zalunardo B, LATVIA: Kigitovica D, Skride A, Strautmane S, PORTUGAL: Ferreira M, Guedes C, REPUBLIC OF MACEDONIA: Bosevski M, Zdraveska M, SWITZERLAND: Bounameaux H, Mazzolai L, USA: Caprini JA, Weinberg I, Wilkins H, VIETNAM: Bui HM.

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Authors and Affiliations

  1. Department of Internal Medicine, Hospital Universitario, 12 de Octubre, Avenida de Córdoba s/n 28041, Madrid, Spain

    Covadonga Gómez-Cuervo

  2. Department of Pneumonology, Hospital Universitario Araba, Álava, Spain

    Agustina Rivas

  3. Department of Vascular Medicine, Ospedale Castelfranco Veneto, Castelfranco Veneto, Italy

    Adriana Visonà

  4. Department of Internal Medicine, Hospital Universitario, de La Princesa, Madrid, Spain

    Nuria Ruiz-Giménez

  5. Department of Internal Medicine, Hospital Universitario Reina Sofía, Córdoba, Spain

    Ángeles Blanco-Molina

  6. Department of Internal Medicine, Hospital General de Granollers, Barcelona, Spain

    Inmaculada Cañas

  7. Department of Internal Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

    José Portillo

  8. Department of Pneumonology, Hospital General, Universitario de Albacete, Albacete, Spain

    Patricia López-Miguel

  9. Department of Hematology, Hospital Universitario General de Cataluña, Barcelona, Spain

    Katia Flores

  10. Department of Internal Medicine, Hospital Germans Trias i Pujol, Universidad Autónoma de Barcelona, Badalona, Barcelona, Spain

    Manuel Monreal

Authors
  1. Covadonga Gómez-Cuervo
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  2. Agustina Rivas
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  3. Adriana Visonà
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  4. Nuria Ruiz-Giménez
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  5. Ángeles Blanco-Molina
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  6. Inmaculada Cañas
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  7. José Portillo
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  8. Patricia López-Miguel
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  9. Katia Flores
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  10. Manuel Monreal
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Consortia

the RIETE Investigators

  • Paolo Prandoni
  • , Benjamin Brenner
  • , Dominique Farge-Bancel
  • , Raquel Barba
  • , Pierpaolo Di Micco
  • , Laurent Bertoletti
  • , Sebastian Schellong
  • , Inna Tzoran
  • , Abilio Reis
  • , Marijan Bosevski
  • , Henri Bounameaux
  • , Radovan Malý
  • , Peter Verhamme
  • , Joseph A. Caprini
  •  & Hanh My Bui

Contributions

Substantial contributions to conception and design of the work: CGC and MM. Substantial contributions to the acquisition, analysis, and interpretation of data for the work: CGC, AR, AV, NRG, ABM, IC, JP, PLM, KF, MM. Drafting of the work or revising it critically for important intellectual content: CGC, and MM. All the authors approved the final version to be published.

Corresponding author

Correspondence to Covadonga Gómez-Cuervo.

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Conflict of interest

Dr. Gómez-Cuervo reports non-financial support from Leo Pharma and Sanofi, outside the submitted work. No other potential conflicts of interest associated with this work.

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The mmebers of the RIETE investigators is given in the ‘Acknowledgments’.

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Gómez-Cuervo, C., Rivas, A., Visonà, A. et al. Predicting the risk for major bleeding in elderly patients with venous thromboembolism using the Charlson index. Findings from the RIETE. J Thromb Thrombolysis 51, 1017–1025 (2021). https://doi.org/10.1007/s11239-020-02274-6

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