Rational Pharmacotherapy in Cardiology

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Large randomized clinical trials (RCTs) in patients with non-valvular atrial fibrillation (AF) showed that new direct oral anticoagulants (DOACs) were just as effective at preventing stroke and systemic thromboembolic (STE) complications as warfarin, although DOACs were associated with less risk of intracranial bleeding. There was significant increasing number of publications addressed to use of DOACs in real-world setting in recent years. We discussed some of pros and cons for studies used real-world data in the review. Results of real-world studies provided a generally strong support for conclusions of main RCTs. In comparison of different DOACs against each other apixaban demonstrated lower bleeding risk while patients given rivaroxaban appeared to have higher rate of hemorrhagic events. High adherence to apixaban treatment for AF irrespective to additional value educational program suggested that apixaban treatment is easy to follow and well accepted by patients despite of twice-daily dosing regimen. Healthcare cost analyses demonstrated that patients who were prescribed apixaban had lower stroke/STE-related as well as major bleeding-related medical costs.

About the Authors

Zh. D. Kobalava
Peoples' Friendship University of Russia (RUDN University)
Russian Federation

Zhanna D. Kobalava – MD, PhD, Professor, Head of Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Head of Chair of Internal Medicine, Cardiology and Functional Diagnostics of the Faculty of Advanced Training of Medical Workers, Medical Institute

Miklukho-Maklaya ul. 6, Moscow, 117198

S. V. Villevalde
Peoples' Friendship University of Russia (RUDN University)
Russian Federation

Svetlana V. Villevalde – MD, PhD, Professor, Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Medical Institute

Miklukho-Maklaya ul. 6, Moscow, 117198

A. A. Shavarov
Peoples' Friendship University of Russia (RUDN University)
Russian Federation

Andrey A. Shavarov – MD, PhD, Associate Professor, Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics

Miklukho-Maklaya ul. 6, Moscow, 117198


1. Wolf P.A., Abbott R.D., Kannel W.B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983-8. doi: 10.1161/01.STR.22.8.983.

2. Savelieva I., Camm A.J. Practical considerations for using novel oral anticoagulants in patients with atrial fibrillation. Clin Cardiol. 2014;37:32-47. doi:10.1002/clc.22204.

3. Macedo A.F., Bell J., McCarron C., et al. Determinants of oral anticoagulation control in new warfarin patients: analysis using data from Clinical Practice Research Datalink. Thromb Res. 2015;136:25060. doi:10.1016/j.thromres.2015.06.007.

4. Fang M.C., Go A.S., Chang Y., et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2010;3:624-31. doi:10.1161/CIRCOUTCOMES.110.937680.

5. Zalesak M., Siu K., Francis K., et al. Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes. 2013;6:567-74. doi:10.1161/CIRCOUTCOMES.113.000192.

6. Ruff C.T., Giugliano R.P., Braunwald E., et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-¬analysis of randomised trials. Lancet. 2014;383:955-62. doi:10.1016/S0140-6736(13)62343-0.

7. Kirchhof P., Benussi S., Kotecha D., et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;18:1609-78. doi: 10.1016/j.rec.2016.11.033.

8. Sulimov V.A., Golitsyn J.V., Panchenko E.P., et al. Diagnosis and treatment of atrial fibrillation. Clinical guidelines. Russian Journal of Cardiology. 2013;4(suppl 3):1-100. (In Russ.)

9. Fosbol E.L., Vinding N.E., Lamberts M., et al. Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation. Europace. 2017;0:1-9. doi:10.1093/europace/eux193.

10. Boriani G., Cimaglia P., Fantecchi E., et al. Non-valvular atrial fibrillation: potential clinical implications of the heterogeneous definitions used in trials on new oral anticoagulants. J Cardiovasc Med (Hagerstown). 2015;16:491-6. doi: 10.2459/JCM.0000000000000236.

11. Grzhibovsky A.M., Ivanov S.V. Cohort studies in health care. Nauka i Zdravoohranenie. 2015;3: 516 (In Russ.)

12. Grzhibovsky A.M., Ivanov S.V. Cross-sectional (one-stage) studies in public health. Nauka i Zdravoohranenie. 2015;2:5-18. (In Russ.)

13. Garrison L.P. Jr., Neumann P.J., Erickson P, et al. Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force Report. Value Health. 2007;10:326-335. doi: 10.1111/j.1524-4733.2007.00186.x.

14. Fairies D.E., Leon A.C., Haro J.M., Obenchain R.L. Analysis of observational healthcare data using SAS. Cary, NC: SAS Institute, Inc.; 2010.

15. Riley G.F. Administrative and claims records as sources of health care cost data. Med Care. 2009;47:S51-S551. doi:10.1097/MLR.0b013e31819c95aa.

16. Annemans L., Aristides A., Kubin M. Real-Life Data: A Growing Need. ISPOR Connections. 2007,13(5):8-12.

17. Johnson M.L., Crown W., Martin B.C., et al. Good research practices for comparative effectiveness research: analytic methods to improve causal inference from nonrandomized studies of treatment effects using secondary data sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force ReportPart III. Value Health. 2009;8:1062-73. doi: 10.1111/j.15244733.2009.00602.x.

18. Yao X., Abraham N.S., Sangaralingham L.R., et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. Am Heart Assoc. 2016;5:e003725. doi:10.1161/JAHA.116.003725.

19. Amin A., Keshishian A., Trocio J., et al. Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States Medicare population. Curr Med Res Opin. 2017;33(9):1595-1604. doi:10.1080/03007995.2017.1345729.

20. Larsen T.B., Skjoth F., Nielsen B., et al. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. Br Med J. 2016;353:i3189. doi:10.1136/bmj.i3189.

21. Tepper P., Mardekian J., Masseria C., et al. Real¬world comparison of bleeding risks among non¬valvular atrial fibrillation patients on apixaban, dabigatran, rivaroxaban: cohorts comprising new initiators and/or switchers from warfarin. Eur Heart J. 2015;36(Abstract Suppl.):339.

22. Noseworthy P.A., Yao X., Abraham N.S., et al. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in non-valvular atrial fibrillation. Chest 2016;150(6):130212. doi:10.1016/j.chest.2016.07.013.

23. Lip G.Y., Keshishian A., Kamble S., et al. Real-world comparison of major bleeding risk among nonvalvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin. Thromb Haemost. 2016;116(5):975-86. doi: 10.1160/TH16-05-0403.

24. Li X., Deitelzweig S., Keshishian A., et al. Effectiveness and safety of apixaban versus warfarin in nonvalvular atrial fibrillation patients in "real-world" clinical practice. A propensity-matched analysis of 76,940 patients. Thromb Haemost. 2017;117:1072-82. doi:10.1160/TH17-01-0068.

25. Deitelzweig S., Luo X., Gupta K., et al. Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients. Curr Med Res Opin. 2017;33(10):1745-54. doi:10.1080/03007995.2017.1334638.

26. Lin J., Trocio J., Gupta K., et al. Major bleeding risk and healthcare economic outcomes of nonvalvular atrial fibrillation patients newly initiated with oral anticoagulant therapy in the real-world setting. J Med Econ. 2017;20(9):952-61. doi:10.1080/13696998.2017.1341902.

27. Zhang Z., Peluzo M.J., Gross C.P., et al. Adherence reporting in randomized controlled trials. Clin Trial. 2014;11(2):195-204. doi:10.1177/1740774513512565.

28. Amara W., Larsen T.B., Sciaraffia E., et al. Patients' attitude and knowledge about oral anticoagulation therapy: results of a self-assessment survey in patients with atrial fibrillation conducted by the European Heart Rhythm Association. Europace. 2016:18;151-5. doi:10.1093/europace/euv317.

29. Lane D.A., Barker R.V., Lip G.Y. Best practice for atrial fibrillation patient education. Curr Pharm Des. 2014;21:533-43. doi:10.2174/13816128/20666140825125715.

30. Potpara T.S., Pison L., Larsen T.B., et al. How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey. Europace. 2015;17:468-72. doi:10.1093/europace/euv025.

31. Yao X., Abraham N.S., Alexander C., et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc. 2016;5:e003074. doi:10.1161/JAHA.115.003074.

32. Montalescot G. Adherence and persistence to apixaban treatment in patients with non-valvular atrial fibrillation is high and similar with standard of care patient education or with an additional educational program: the randomized AEGEAN study. Circulation. 2016;134:A18842.

33. Pan X., Kachroo S., Liu X., et al. Real world discontinuation rates with apixaban versus warfarin, dabigatran, or rivaroxaban among atrial fibrillation patients newly initiated on anticoagulation therapy: early findings. J Am Coll Cardiol. 2014;63:A415. doi:10.1016/S0735-1097(14)60415-0.

34. Brown J.D., Shewale A.R., Talbert J.C. Adherence to rivaroxaban, dabigatran, and apixaban for stroke prevention in incident, treatment-naive nonvalvular atrial fibrillation. J Manag Care Spec Pharm. 2016;22(11):1319-29. doi:10.18553/jmpc.2016.22.11.1319.

35. Andrade J.G., Krahn A.D., Skanes A.C., et al. Values and preferences of physicians and patients with nonvalvular atrial fibrillation who receive oral anticoagulation therapy for stroke prevention. Can J Cardiol. 2016;32(6):747-53. doi:10.1016/j.cjca.2015.09.023.

36. Vrijens B., Heidbuchel H. Non-vitamin K antagonist oral anticoagulants: considerations on oncevs. twice-daily regimens and their potential impact on medication adherence. Europace. 2015;17(4):514-23. doi:10.1093/europace/euu311.

For citation:

Kobalava Z.D., Villevalde S.V., Shavarov A.A. NEW DIRECT ORAL ANTICOAGULANTS FOR TREATMENT OF PATIENTS WITH ATRIAL FIBRILLATION IN REAL-WORLD SETTING. Rational Pharmacotherapy in Cardiology. 2018;14(2):298-305. (In Russ.)

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