Algorithm for the Choice of Anticoagulant for Patients with Atrial Fibrillation

Aim. To evaluate the effectiveness of the anticoagulant choice algorithm in the prevention of complications of atrial fibrillation (AF).

Material and methods. Patients with AF (n=98) were included into observational prospective study. The level of adherence to treatment, risk of food interactions and presence of CYP2C9 and VKORC1 genes mutations were determined at the initial examination. These indicators were necessary to specify an eligible anticoagulant according to the evaluated algorithm. Therapy was prescribed by the attending physician. Hemorrhagic and thromboembolic complications were assessed at the next examination after 24 weeks.

Results. Hemorrhagic complications were observed in 31.6% of patients during the follow-up. Their number was comparable in individuals taking antiplatelet agents and direct oral anticoagulants (DOACs) (χ²=1.44; p<0.49, Pearson) and significantly more in individuals taking warfarin (as compared to DOACs: χ²=25.08; p<0.000, Pearson; and antiplatelet agents: χ²=34.32; p<0.000, Pearson). Thromboembolic complications were reported in 8.16% of patients. Their number was more in patients taking DOACs than warfarin (χ²=7.03; p<0.03, Pearson). Patients who had to take DOACs according to the algorithm, but in the study took warfarin, demonstrated significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Patients who could take warfarin according to the algorithm, but in the study took DOACs, had significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications.

Conclusion. The results of the study demonstrated the potential for reduction in complications, especially thromboembolic, in the choice of anticoagulant using the algorithm; and reduction in complications of therapy, primarily with warfarin, due to the initial prescription of DOACs. The proposed approach, which consists in using the quantitative assessment of adherence to treatment, and only if necessary supplemented by the assessment of food preferences and/or pharmacogenetic studies, contributes to the treatment optimization.

1. Diagnosis and treatment of atrial fibrillation. Russian Clinical Recommendations (2017) [cited by Jul 07, 2019]. Available from: https://scardio.ru/content/Guidelines/FP_rkj_13.pdf (In Russ.)

2. January C.T., Wann L.S., Calkins H., et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society. J Am CollCardiol. 2019;74(1):104-32. DOI:10.1016/j.jacc.2019.01.011.

3. Verma A., Cairns J.A., Mitchell L.B., et al. 2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation. Can J Cardiol. 2014;30(10):1114-30. DOI:10.1016/j.cjca.2014.08.001.

4. Kirchhof P., Benussi S., Kotecha D., et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38)2893-962. DOI:10.1093/eurheartj/ehw210.

5. Steffel J., Verhamme P., Potpara T.S., et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330-93. DOI:10.1093/eurheartj/ehy136.

6. Sorensen R., Gislason G., Torp-Pedersen Ch., et al. Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ Open. 2013;3:e002758. DOI:10.1136/bmjopen-2013-002758.

7. Boriani G., Proietti M., Lip G.Y.H., et al. Contemporary stroke prevention strategies in 11 096 european patients with atrial fibrillation: a report from the eurobservational research programmeon atrial fibrillation (EORP-AF) long-term general registry. Europace. 2018;20(5):747-57. DOI:10.1093/europace/eux30.

8. Lip G., Bassand J.P., Fitzmaurice D., et al. Inappropriate utilization of anticoagulation in patients with atrial fibrillation: the global anticoagulant registry in the field (GARFIELD) registry. J Am Coll Cardiol. 2012;59(13):670.

9. O'Brien E.C., Simon D.N., Allen L.A., et al. Reasons for Warfarin Discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J. 2014;168(4):487- 94. DOI:10.1016/j.ahj.2014.07.002.

10. Lip G.Y., Haguenoer K., Saint-Etienne C., et al. Relationship of the SAMeTT(2)R(2) score to poor quality anticoagulation, stroke, clinically relevant bleeding, and mortality in patients with atrial fibrillation. Chest. 2014;146:719-26. DOI:10.1378/chest.13-2976.

11. Albert N.M. Use of novel anticoagulants for patients with atrial fibrillation: systematic review and clinical implications. Heart Lung. 2014;43:48-59. DOI:10.1016/j.hrtlng.2013.10.014.

12. Bockeria O.L., Kopaliani T.I. Cаn we abandon warfarin? Annals of Arrhythmology. 2016;13(2):87- 95 (In Russ.) [Бокерия О.Л., Копалиани Т.И. Откажемся ли мы от варфарина? Анналы Аритмологии. 2016;13(2):87-95]. DOI:10.15275/annaritmol.2016.2.4.

13. Rudakova A.V. Analysis of the influence of thromboembolic complications prevention with oral anticoagulants on budget in patients with non-valvular atrial fibrillation. Rational Pharmacotherapy in Cardiology. 2015;11(3):267-71 (In Russ.) DOI:10.20996/1819-6446-2015-11-3-267-271.

14. Bunin Y.A., Miklishanskaya S.V. Clinical significance of new oral anticoagulants in the prevention of thromboembolic complications in patients with atrial fibrillation: not all dreams come true. Rational Pharmacotherapy in Cardiology. 2016;12(4):465-70 (In Russ.) DOI:10.20996/1819-6446-2016-12-4-465-470.

15. Skirdenko J.P., Nikolayev N.A. New Approaches to Individualized Choice of Oral Anticoagulants in Patients with Atrial Fibrillation. Rational Pharmacotherapy in Cardiology. 2018;14(1):58-64 (In Russ.) DOI:10.20996/1819-6446-2018-14-1-58-64.

16. Skirdenko Y.P., Nikolaev N.A. Contribution of anticoagulant therapy adherence to the risk of complications of atrial fibrillation. Russian Journal of Cardiology. 2019;(2):64-9 (In Russ.) DOI:10.15829/1560-4071-2019-2-64-69.

17. Lehr R. Sixteen s squared over d squared: a relation for crudesample size estimates. Statistics in Medicine. 1992;11:1099-102.

18. Nikolaev N.A., Martynov A.I., Drapkina O.M., et al. The first Russian consensus on the quantitativeassessment of the adherence to treatment. Therapy. 2018; 5:11-32 (In Russ.) DOI:10.18565/Therapy.2018;5[23]:11-32.

19. Nikolaev N.A., Skirdenko Yu.P., Livzan M.A., et al. Clinically important dietary preferences:evaluation, analysis, interpretation. Farmateka. 2018;9:85-8 (In Russ.) DOI:10.18565/pharmateca.2018.9.85-88.

20. Kakkar A.K., Mueller I., Bassand J.P., et al. International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD). Am Heart J. 2012;163(1):13-19.e1. DOI:10.1016/j.ahj.2011.09.09.011.