Advertisement

Internal and Emergency Medicine

, Volume 14, Issue 8, pp 1307–1315 | Cite as

The effect of management models on thromboembolic and bleeding rates in anticoagulated patients: an ecological study

  • Alberto TosettoEmail author
  • Sophie Testa
  • Gualtiero Palareti
  • Oriana Paoletti
  • Ilaria Nichele
  • Francesca Catalano
  • Rossella Morandini
  • Maria Di Paolo
  • Maurizio Tala
  • Pilar Esteban
  • Francesco Cora’
  • Salvatore Mannino
  • Anna Maroni
  • Maria Sessa
  • Giancarlo Castaman
IM - ORIGINAL
Part of the following topical collections:
  1. Direct Oral Anticoagulants

Abstract

The primary study objective is to compare the outcomes of patients taking oral anticoagulant medications in two distinct populations treated according to different management models (comprehensive vs. usual care). (Design: regional prospective cohort study; setting: hospital admission data from two regions). Eligible partecipants were patients taking oral anticoagulant drugs (vitamin K antagonist or direct oral anticoagulants), residents in the Vicenza and Cremona districts from February 1st, 2016 to June 30th, 2017. Patients were identified by accessing the administrative databases of patient drug prescriptions. The primary study outcome was admission to the Emergency Department for stroke, systemic arterial embolism, recurrence of venous thromboembolism or major bleeding. The study evaluated outcomes in 14,226 patients taking oral anticoagulants, of whom 6725 being followed in Cremona with a comprehensive management model. There were 19 and 45 thromboembolic events over 6205 and 6530 patient-years in the Cremona and Vicenza cohort, respectively (IRR 0.44, 95% CI 0.24–0.77). The reduction of events in the Cremona cohort was almost entirely explained by a decrease of events in patients taking VKA (IRR 0.41, 95% CI 0.20–0.78) but not DOACs (IRR 1.08, 95% CI 0.25–5.24). The rate of major bleeding was non-significantly higher in Cremona than in Vicenza (IRI 1.32; 95% CI 0.74–2.40). Across the two cohorts, the risk of bleeding was lower in patients being treated with DOACs rather than warfarin (10/4574 vs. 42/8161 event/person-years, respectively, IRR 0.42 95% CI 0.19–0.86). We conclude that a comprehensive management model providing centralized dose prescription and follow-up may significantly reduce the rate of thromboembolic complications, without substantially increasing the number of bleeding complications. Patients treated with direct oral anticoagulants appear to have a rate of thromboembolic complications comparable to VKA patients under the best management model, with a reduction of major bleeding.

Keywords

Vitamin K antagonists Direct oral anticoagulants Complications 

Notes

Author contributions

AT and ST contributed equally to the manuscript. AT designed the study, analyzed the data, and wrote the manuscript. He has received travel funding from Bayer and Novo-Nordisk; lecture fees from Stago, Werfen, and Roche. ST designed the study and wrote the manuscript. She declares lecture fees from Bayer, Stago, Roche, Boheringer, Sobi, Daiichi, BMS Pfizer, and Sanofi. GP revised the manuscript for important intellectual content. He declares participation to advisory boards for Alfasigma, Pfizer, Roche; lectures fees from Werfen. FC, MP, PE, RM, IN, OP, and MT collected the data. FC, SM, and AM contributed to the study design and administrative data collection. MS and GC revised the data and critically revised the manuscript for important intellectual content and adjudicated events

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no conflict of interest.

Statement of human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Cremona and Vicenza Institutional Review Boards and with the 1964 Helsinki declaration and its later amendments (see also Ethics, funding and data sharing paragraph). This article does not contain any studies with animals performed by any of the author.

Informed consent

For this type of observational study, formal consent is not required.

References

  1. 1.
    Huisman MV, Rothman KJ, Paquette M, Teutsch C, Diener HC, Dubner SJ, Halperin JL, Ma C, Zint K, Elsaesser A, Bartels DB, Lip GY (2015) Antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation: the GLORIA-AF Registry, Phase II. Am J Med 128(12):1306–1313.e1301.  https://doi.org/10.1016/j.amjmed.2015.07.013 CrossRefPubMedGoogle Scholar
  2. 2.
    Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS (2016) US emergency department visits for outpatient adverse drug events, 2013–2014. JAMA 316(20):2115–2125.  https://doi.org/10.1001/jama.2016.16201 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Georg Haeusler K, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbuchel H, Group ESCSD (2018) The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary. Europace.  https://doi.org/10.1093/europace/euy054 CrossRefGoogle Scholar
  4. 4.
    Italian Federation of Thrombosis Centers (FCSA) (2003) A guide to oral anticoagulant treatment. Haematologica 88(Suppl 2):52Google Scholar
  5. 5.
    Ansell J, Hirsh J, Dalen J, Bussey H, Anderson D, Poller L, Jacobson A, Deykin D, Matchar D (2001) Managing oral anticoagulant therapy. Chest 119(1):22S–38S.  https://doi.org/10.1378/chest.119.1_suppl.22S CrossRefPubMedGoogle Scholar
  6. 6.
    Beyth RJ, Quinn LM, Landefeld CS (1998) Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 105(2):91–99CrossRefGoogle Scholar
  7. 7.
    Landefeld CS, Goldman L (1989) Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med 87(2):144–152CrossRefGoogle Scholar
  8. 8.
    Chiquette E, Amato M, Bussey H (1998) Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. Arch Intern Med 158(15):1641–1647CrossRefGoogle Scholar
  9. 9.
    van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ (2006) Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 129(5):1155–1166.  https://doi.org/10.1378/chest.129.5.1155 CrossRefPubMedGoogle Scholar
  10. 10.
    Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, Healey JS, Yusuf S (2008) Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 118(20):2029–2037.  https://doi.org/10.1161/circulationaha.107.750000 CrossRefPubMedGoogle Scholar
  11. 11.
    Nieuwlaat R, Connolly BJ, Hubers LM, Cuddy SM, Eikelboom JW, Yusuf S, Connolly SJ (2012) Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study. Thromb Res 129(6):715–719.  https://doi.org/10.1016/j.thromres.2011.08.024 CrossRefPubMedGoogle Scholar
  12. 12.
    Palareti G, Legnani C, Guazzaloca G, Lelia V, Cosmi B, Lunghi B, Marchetti G, Poli D, Pengo V (2005) Risks factors for highly unstable response to oral anticoagulation: a case-control study. Br J Haematol 129(1):72–78.  https://doi.org/10.1111/j.1365-2141.2005.05417.x CrossRefPubMedGoogle Scholar
  13. 13.
    Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, Shehab N, Mock J, Myers T, Dentali F, Crowther MA, Agarwal A, Bhatt M, Khatib R, Riva JJ, Zhang Y, Guyatt G (2018) American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2(22):3257–3291.  https://doi.org/10.1182/bloodadvances.2018024893 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955–962.  https://doi.org/10.1016/S0140-6736(13)62343-0 CrossRefGoogle Scholar
  15. 15.
    Mazurek M, Huisman MV, Rothman KJ, Paquette M, Teutsch C, Diener H-C, Dubner SJ, Halperin JL, Zint K, França LR, Lu S, Lip GYH (2018) Gender differences in antithrombotic treatment for newly diagnosed atrial fibrillation: the GLORIA-AF Registry Program. Am J Med 131(8):945–955.e943.  https://doi.org/10.1016/j.amjmed.2018.03.024 CrossRefPubMedGoogle Scholar
  16. 16.
    Thompson LE, Maddox TM, Lei L, Grunwald GK, Bradley SM, Peterson PN, Masoudi FA, Turchin A, Song Y, Doros G, Davis MB, Daugherty SL (2017) Sex differences in the use of oral anticoagulants for atrial fibrillation: a report from the National Cardiovascular Data Registry (NCDR (®)) PINNACLE Registry. J Am Heart Assoc Cardiovasc Cerebrovasc Dis 6(7):e005801.  https://doi.org/10.1161/JAHA.117.005801 CrossRefGoogle Scholar
  17. 17.
    Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH (2010) Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 123(7):638–645.e634.  https://doi.org/10.1016/j.amjmed.2009.11.025 CrossRefPubMedGoogle Scholar
  18. 18.
    Morgenstern H (1995) Ecologic studies in epidemiology: concepts, principles, and methods. Annu Rev Public Health 16:61–81.  https://doi.org/10.1146/annurev.pu.16.050195.000425 CrossRefPubMedGoogle Scholar
  19. 19.
    Testa S, Alatri A, Paoletti O, Morstabilini G, Medagliani MA, Denti N, Martellenghi E (2006) Reorganisation of an anticoagulation clinic using a telemedicine system: description of the model and preliminary results. Intern Emerg Med 1(1):24–29CrossRefGoogle Scholar
  20. 20.
    Tosetto A, Manotti C, Marongiu F, Italian Federation of Anticoagulation Clinics clinical quality study g (2015) Center-related determinants of vka anticoagulation quality: a prospective multicenter evaluation. PLoS ONE 10(12):e0144314.  https://doi.org/10.1371/journal.pone.0144314 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Istituto Nazionale di Statistica (ISTAT) (2017) Istat. Popolazione residente al 1° gennaio. https://dati.istat.it/Index.aspx?DataSetCode=DCIS_POPRES1. Accessed 30 Apr 2017
  22. 22.
    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381.  https://doi.org/10.1016/j.jbi.2008.08.010 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Sorensen R, Gislason G, Torp-Pedersen C, Olesen JB, Fosbol EL, Hvidtfeldt MW, Karasoy D, Lamberts M, Charlot M, Kober L, Weeke P, Lip GY, Hansen ML (2013) Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ Open.  https://doi.org/10.1136/bmjopen-2013-002758 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    World Health Organization (2017) World Standard Population. https://apps.who.int/healthinfo/statistics/mortality/whodpms/definitions/pop.htm. Accessed 16 Apr 2018
  25. 25.
    R Development Core Team (2016) R: a language and environment for statistical computing (v 3.3.2). R Foundation for Statistical Computing, ViennaGoogle Scholar
  26. 26.
    Fay MP, Feuer EJ (1997) Confidence intervals for directly standardized rates: a method based on the gamma distribution. Stat Med 16(7):791–801CrossRefGoogle Scholar
  27. 27.
    Dixon RF, Rao L (2014) Asynchronous virtual visits for the follow-up of chronic conditions. Telemed J e-health 20(7):669–672.  https://doi.org/10.1089/tmj.2013.0211 CrossRefPubMedGoogle Scholar
  28. 28.
    Klonoff DC (2009) Using telemedicine to improve outcomes in diabetes–an emerging technology. J Diabetes Sci Technol 3(4):624–628.  https://doi.org/10.1177/193229680900300401 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Barcellona D, Fenu L, Cornacchini S, Marongiu F (2013) Telemedicine can improve the quality of oral anticoagulation using portable devices and self-testing at home. J Telemed Telecare 19(6):298–301.  https://doi.org/10.1177/1357633x13501764 CrossRefPubMedGoogle Scholar
  30. 30.
    Barcellona D, Fenu L, Marongiu F (2017) Point-of-care testing INR: an overview. Clin Chem Lab Med 55(6):800–805.  https://doi.org/10.1515/cclm-2016-0381 CrossRefPubMedGoogle Scholar
  31. 31.
    Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146(12):857–867CrossRefGoogle Scholar
  32. 32.
    Dentali F, Riva N, Crowther M, Turpie AG, Lip GY, Ageno W (2012) Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation 126(20):2381–2391.  https://doi.org/10.1161/CIRCULATIONAHA.112.115410 CrossRefPubMedGoogle Scholar
  33. 33.
    van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV (2014) Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 12(3):320–328.  https://doi.org/10.1111/jth.12485 CrossRefPubMedGoogle Scholar
  34. 34.
    Hart J (2011) On ecological studies: a short communication. Dose Response 9(4):497–501.  https://doi.org/10.2203/dose-response.10-046.Hart CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR (2011) Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs Study to Improve Anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes 4(1):22–29.  https://doi.org/10.1161/circoutcomes.110.957738 CrossRefPubMedGoogle Scholar
  36. 36.
    Yao X, Abraham NS, Alexander GC, Crown W, Montori VM, Sangaralingham LR, Gersh BJ, Shah ND, Noseworthy PA (2016) Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc.  https://doi.org/10.1161/jaha.115.003074 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, Kowey PR, Mahaffey KW, Naccarelli G, Reiffel J, Singer DE, Peterson ED, Piccini JP (2016) Off-label dosing of non-vitamin K antagonist oral anticoagulants and adverse outcomes: the ORBIT-AF II Registry. J Am Coll Cardiol 68(24):2597–2604.  https://doi.org/10.1016/j.jacc.2016.09.966 CrossRefPubMedGoogle Scholar

Copyright information

© Società Italiana di Medicina Interna (SIMI) 2019

Authors and Affiliations

  • Alberto Tosetto
    • 1
    Email author
  • Sophie Testa
    • 2
  • Gualtiero Palareti
    • 3
  • Oriana Paoletti
    • 2
  • Ilaria Nichele
    • 1
  • Francesca Catalano
    • 2
  • Rossella Morandini
    • 2
  • Maria Di Paolo
    • 1
  • Maurizio Tala
    • 2
  • Pilar Esteban
    • 2
  • Francesco Cora’
    • 4
  • Salvatore Mannino
    • 5
  • Anna Maroni
    • 6
  • Maria Sessa
    • 7
  • Giancarlo Castaman
    • 8
  1. 1.Haemostasis and Thrombosis Unit, Haematology DepartmentSan Bortolo HospitalVicenzaItaly
  2. 2.Haemostasis and Thrombosis CentreCremona HospitalCremonaItaly
  3. 3.Arianna Anticoagulazione FoundationBolognaItaly
  4. 4.Emergency DepartmentSan Bortolo HospitalVicenzaItaly
  5. 5.ATS ValpadanaCremonaItaly
  6. 6.Territorial Pharmacy UnitSan Bortolo HospitalVicenzaItaly
  7. 7.Neurology DivisionCremona HospitalCremonaItaly
  8. 8.Department of Oncology, Centre for Bleeding Disorders and CoagulationCareggi University HospitalFlorenceItaly

Personalised recommendations