New oral anti-coagulants versus vitamin K antagonists in high thromboembolic risk patients

Autoři: Annachiara Bellin aff001;  Patrizia Berto aff002;  Sakis Themistoclakis aff003;  Aastha Chandak aff002;  Pietro Giusti aff001;  Giacomo Cavalli aff001;  Sumeet Bakshi aff002;  Michele Tessarin aff003;  Paola Deambrosis aff004;  Alessandro Chinellato aff003
Působiště autorů: Università degli studi di Padova, Padova, Italia aff001;  Analytica-Laser, a Certara company, Londra, United Kingdom aff002;  LHU 3 Serenissima, Venezia, Italia aff003;  LHU 2 Marca Trevigiana, Treviso, Italia aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222762



Oral anticoagulant therapy (VKA) is nowadays the mainstay of treatment in primary and secondary stroke prevention in patients with atrial fibrillation. Given the limited risk-benefit ratio of vitamin K antagonists, pharmacological research has been directed towards the development of products that could overcome these limits, new oral anticoagulants were recently introduced: dabigatran, rivaroxaban, apixaban, and edoxaban.


Scope of the present study was to examine patterns of use, effectiveness, safety and mean annual cost per patient of anticoagulant treatment for non-valvular AF in real clinical practice.


A retrospective observational cohort study, by using administrative databases (drugs, hospitalizations, clinical visits, lab tests, population registry), was conducted in the Local Health Unit (LHU) of Treviso, Italy, from January 1, 2012 to December 31, 2016.


5597 subjects were selected, 2171 of which satisfied all inclusion criteria. In particular 1355 patients were treated with VKA, 577 patients were treated with NOAC, and 239 patients were treated initially with VKA and subsequently switched to NOAC (switch group). NOAC treatment showed to be superior to VKA and this superiority was statistically significant on both end-points: patients in the NOAC group reported less cardiovascular events (9,9%) and less bleeding episodes (5,5%) versus VKA patients (14,6% and 11,4%; p<,0001 and p = 0,0049, respectively).

The mean cost per patient per year was respectively € 1323,9 for patients treated with NOAC versus € 1003,3 for patients treated with VKA. Cost difference appears to be largely driven by drug cost (€ 767,9 for NOAC versus € 17,7 for VKA patients) and by specialist visits and laboratory tests (€ 318,4 for NOAC versus € 733,4 for VKA patients).


In this retrospective real-world study treatment with NOAC showed to be associated with significant reductions of CV events and bleeding events compared to VKA use, albeit at a higher NHS’ direct cost per patient/year, mainly due to higher drug therapy cost.

Klíčová slova:

Atrial fibrillation – Drug therapy – Hemorrhage – Italy – Stroke – Thromboembolism – Anticoagulant therapy – Anticoagulants


1. Lip GYH, Brechin CM, Lane DA. The global burden of atrial fibrillation and stroke: A systematic review of the epidemiology of atrial fibrillation in regions outside North America and Europe. Chest. 2012, p.1489–1498. doi: 10.1378/chest.11-2888 22459778

2. Sanità, Istituto Superiore di. Il Progetto Cuore. Progetto cuore.iss. [Online] 02 11 2018.

3. Inzitari D, Polizzi BM, Roti L, Il Progetto FAI: La Fibrillazione Atriale in Italia. La Medicina di Iniziativa e il Medico di Medicina Generale per garantire l’accesso a servizi e cure efficaci riducendo i costi per il SSN e i costi sociali legati all’elevato rischio di ictus cerebrale. 2017.

4. Bollettino informativo SER del Veneto. Veneto, Regione. 2009.

5. Fedeli U, Avossa F, Ferroni E, Saugo M, Pengo V, Contemporary Burden of Atrial Fibrillation and Associated Mortality in Northeastern Italy. American Journal of Cardiology, 2016; p. 720–724.

6. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al.,Worldwide epidemiology of atrial fibrillation: A global burden of disease 2010 study. Circulation. 2014; p. 837–47.

7. Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ, Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart, 2004; p. 286–292. doi: 10.1136/hrt.2002.008748 14966048

8. Wolf PA, Abbott RD, Kannel WB, Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke, 1991; 22(8):983–988. doi: 10.1161/01.str.22.8.983 1866765

9. Hart RG, Pearce LA, Aguilar MI, Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Annals of internal medicine, 2007;146(12):857–67. doi: 10.7326/0003-4819-146-12-200706190-00007 17577005

10. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al, RE-LY Steering Commit- tee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, 2009; 361:1139–1151. doi: 10.1056/NEJMoa0905561 19717844

11. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al., ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med, 2011, p.365: 981–992.

12. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al., ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011, p. 365:883–891. doi: 10.1056/NEJMoa1009638 21830957

13. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al., Investigators EA-T. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med, 2013, p. 369:2093–2104. doi: 10.1056/NEJMoa1310907 24251359

14. Trifirò G., Sultana J., Bate A., From Big Data to Smart Data for Pharmacovigilance: The Role of Healthcare Databases and Other Emerging Sources. Drug Safety 2018, pag. 143–149 doi: 10.1007/s40264-017-0592-4 28840504

15. Trifirò G, Gini R, Barone-Adesi F, Beghi E, Cantarutti A, Capuano A, et al., The Role of European Healthcare Databases for Post-Marketing Drug Effectiveness, Safety and Value Evaluation: Where Does Italy Stand?, Drug Safety 2019, pag. 347–363 doi: 10.1007/s40264-018-0732-5 30269245

16. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al., ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European heart journal, 2016, p. 37 (389): 2893–962. doi: 10.1093/ehjcvp/pvw022

17. Deambrosis P, Bettiol A, Bolcato J, Pirolo R, Franchin G, Chinellato A. et al., Real-practice thromboprophylaxis in atrial fibrillation. Acta Pharmaceutica, 2017; p. 227–236. doi: 10.1515/acph-2017-0016 28590907

18. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Conti JB, et al., 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 Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 2014, p. 2;64(21):e1-76.

19. Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a real world atrial fibrillation population: a modelling analysis based on a nationwide cohort study.Thrombosis and haemostasis, 2012; 107.3: 584p. 125–131. doi: 10.1160/TH11-11-0784 22186961

20. Esteve-Pastor MA, Rivera-Caravaca JM, Roldán V, Vicente V, Romiti GF, Romanazzi I, et al., Estimated absolute effects on efficacy and safety outcomes of using non-vitamin K antagonist oral anticoagulants in real-world atrial fibrillation patients: A comparison with optimally acenocoumarol anticoagulated patients. International journal of cardiology, 2018; p. 254, 125–131.

21. Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH, Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke, 2017; p. 2494–2503. doi: 10.1161/STROKEAHA.117.017549 28716982

22. Bouillon K, Bertrand M, Maura G, Blotière PO, Ricordeau P, Zureik M, Risk of bleeding and arterial thromboembolism in patients with non-valvular atrial fibrillation either maintained on a vitamin K antagonist or switched to a non-vitamin K-antagonist oral anticoagulant: a retrospective, matched-cohort study. The Lancet Haematology, 2015; p. e150–e159. doi: 10.1016/S2352-3026(15)00027-7 26687957

23. Beyer-Westendorf J, Gelbricht V, Förster K, Ebertz F, Röllig D, Schreier T, Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care–results from the D resden NOAC registry. British journal of clinical pharmacology, 2014; p. 908–917.

24. Deitelzweig S, Amin A, Jing Y, Makenbaeva D, Wiederkehr D, Lin J, et al., Medical cost reductions associated with the usage of novel oral anticoagulants vs warfarin among atrial fibrillation patients, based on the RE-LY, ROCKET-AF, and ARISTOTLE trials. Journal of medical economics, 2012; p. 776–785. doi: 10.3111/13696998.2012.680555 22449118

25. Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S, et al., Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. Value in health, 2013; p. 498–506. doi: 10.1016/j.jval.2013.01.009 23796283

26. Harrington AR, Armstrong EP, Nolan PE Jr, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke, 2013; p. 1676–1681. doi: 10.1161/STROKEAHA.111.000402 23549134

27. Rognoni C1, Marchetti M, Quaglini S, Liberato NL, Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clinical Drug Investigation, 2014; p. 9–17. doi: 10.1007/s40261-013-0144-3 24135964

28. López-López JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al., Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BJM, 2017.

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