Safety and efficacy of treatment with vitamin K antagonists in patients managed in a network of anticoagulation services or as routine general care

Gianfranco De Girolamo; Luca Sarti; Sonia Cecoli; Karin Bonora; Chiara  Ajolfi; Francesco Bellelli; Valeria Coluccio; Gualtiero Palareti; Marco Marietta

doi:10.4081/btvb.2022.9

Authors

Gianfranco De Girolamo Department of Public Health, Epidemiology and Risk Communication Unit, Azienda Unità Sanitaria Locale di Modena, Italy.
Luca Sarti Internal and Emergency Medicine Unit, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile Baggiovara, Italy.
Sonia Cecoli Servizio Interaziendale Ingegneria Clinica, Azienda Unità Sanitaria Locale di Modena, Italy.
Karin Bonora Department of Public Health, Epidemiology and Risk Communication Unit, Azienda Unità Sanitaria Locale di Modena, Italy.
Chiara Ajolfi Local Pharmaceutical Department, Azienda Unità Sanitaria Locale di Modena, Italy.
Francesco Bellelli Dipartimento Aziendale di Cure Primarie - U.O. Cure Primarie Distretto di Modena, Azienda Unità Sanitaria Locale di Modena, Italy.
Valeria Coluccio Hematology Unit, Azienda Ospedaliero-Universitaria di Modena, Ospedale Policlinico, Modena, Italy.
Gualtiero Palareti Arianna Anticoagulazione Foundation, Bologna, Italy.
Marco Marietta
marco.marietta1@gmail.com
Hematology Unit, Azienda Ospedaliero-Universitaria di Modena, Ospedale Policlinico, Modena, Italy.

This is a retrospective, record-linkage study aimed at comparing the effectiveness and safety of two management models of vitamin K antagonists: a Network model (NAS), in which anticoagulation clinics and general practitioners (GP) share the same management software and database, and an individual General Practitioners model. Main outcomes were thromboembolic events (TE), major bleeding (MB) and all-cause mortality. Crude incidence rate and sub-distribution hazard ratio were calculated. Fine and Grey models were used to calculate SHR in multi-variable analysis. 9,418 patients in the NAS and 5,508 in the Routine General Care (RGC) cohort were included. Patients in the NAS cohort had a lower incidence of TE and mortality in respect to the RGC (sHR 0.76%, 95% CI 0.64-0.90 and 0.82%, 95% CI 0.75-0.89, respectively). More patients in the NAS than in the RGC cohort attained a Time in Therapeutic Range >60% (62.2% vs 35.7%, p<0.001). No statistically significant difference was found in MB incidence. This study shows that the NAS model for vitamin K antagonist oral anticoagulants management significantly improves the TTR and reduces the incidence of TE and mortality, without affecting the MB rate.

Ageno W, Gallus AS, Wittkowsky A, et al. Oral Anticoagulant Therapy. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e44–88S. DOI: https://doi.org/10.1378/chest.11-2292

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. DOI: https://doi.org/10.1056/NEJMoa0905561

Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. DOI: https://doi.org/10.1056/NEJMoa1009638

Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92. DOI: https://doi.org/10.1056/NEJMoa1107039

Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-110. DOI: https://doi.org/10.1056/NEJMoa1310907

van der Hulle T, Kooiman J, den Exter PL, et al. 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 2014;12:320-8. DOI: https://doi.org/10.1111/jth.12485

Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013;369:1206-14. DOI: https://doi.org/10.1056/NEJMoa1300615

Grandone E, Aucella F, Barcellona D, et al. Position paper on the safety/efficacy profile of direct oral anticoagulants in patients with chronic kidney disease. Consensus document from the SIN, FCSA and SISET. Blood Transfus 2020;18:478-85.

Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996;335:540-6. DOI: https://doi.org/10.1056/NEJM199608223350802

Palareti G, Legnani C, Cosmi B, et al. Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence. J Thromb Haemost 2005;3:955-61. DOI: https://doi.org/10.1111/j.1538-7836.2005.01330.x

Chiquette E, Amato MG, Bussey HI. Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. Arch Intern Med 1998;158:1641-7. DOI: https://doi.org/10.1001/archinte.158.15.1641

Witt DM, Sadler MA, Shanahan RL, et al. Effect of a centralized clinical pharmacy anticoagulation service on the outcomes of anticoagulation therapy. Chest 2005;127:1515-22. DOI: https://doi.org/10.1378/chest.127.5.1515

Marietta M, Banchelli F, Pavesi P, et al. Direct oral anticoagulants vs vitamin K antagonist in atrial fibrillation: A prospective, propensity score adjusted cohort study. Eur J Intern Med 2019;62:9-16. DOI: https://doi.org/10.1016/j.ejim.2018.12.010

Modena Statistiche. Available from: http://www.modenastatistiche.it/page.asp?IDCategoria=175&IDSezione=8393&cod_sesso=3&cod_tipo_tab=1&excel=no&TipoForm=8&Speciale=Atlante_Output Accessed 29 Mar 2021.

Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69:236-9. DOI: https://doi.org/10.1055/s-0038-1651587

Fine JP, Gray RJ. A Proportional Hazards Model for the Subdistribution of a Competing Risk. J Am Stat Assoc 1999;94:496-509. DOI: https://doi.org/10.1080/01621459.1999.10474144

Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med 2014;33:1242-58. DOI: https://doi.org/10.1002/sim.5984

Austin PC, Fine JP. Practical recommendations for reporting Fine-Gray model analyses for competing risk data. Stat Med 2017;36:4391-400. DOI: https://doi.org/10.1002/sim.7501

Imai K, Ratkovic M. Covariate balancing propensity score. J R Stat Soc B 2014;76:243-63. DOI: https://doi.org/10.1111/rssb.12027

Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 2011;46:399-424. DOI: https://doi.org/10.1080/00273171.2011.568786

Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd edition. Routledge 1988.

Tosetto A, Testa S, Palareti G, et al. The effect of management models on thromboembolic and bleeding rates in anticoagulated patients: an ecological study. Intern Emerg Med 2019;14:1307-15. DOI: https://doi.org/10.1007/s11739-019-02148-7

De Girolamo, G., Sarti, L., Cecoli, S., Bonora, K., Ajolfi, C. ., Bellelli, F., Coluccio, V., Palareti, G., & Marietta, M. (2022). Safety and efficacy of treatment with vitamin K antagonists in patients managed in a network of anticoagulation services or as routine general care. Bleeding, Thrombosis, and Vascular Biology, 1(1). https://doi.org/10.4081/btvb.2022.9