Как нивелировать риск кровотечений на фоне приема антикоагулянтной терапии у пациентов с фибрилляцией предсердий?

Бернс С.А., Барбараш О.Л. Как нивелировать риск кровотечений на фоне приема антикоагулянтной терапии у пациентов с фибрилляцией предсердий? Consilium Medicum. 2022;24(1):36–41.
DOI: 10.26442/20751753.2022.1.201474

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Berns SA, Barbarash OL. How to level the risk of bleeding while taking anticoagulant therapy in patients with atrial fibrillation. Consilium Medicum. 2022;24(1):36–41. DOI: 10.26442/20751753.2022.1.201474

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Аннотация

Фибрилляция предсердий (ФП) относится к наиболее распространенному виду нарушений сердечного ритма, при этом ФП является основным фактором риска развития ишемического инсульта. На протяжении длительного времени к стандарту профилактики тромбоэмболических осложнений у пациентов с ФП относятся антагонисты витамина К, в первую очередь варфарин. Еще 5 лет назад в структуре назначения антикоагулянтов (АК) дабигатран, ривароксабан и апиксабан занимали 2-е место, уступая лидерство варфарину. Общеизвестной причиной неадекватного применения АК является опасность развития кровотечения. Известно большое количество валидированных шкал для оценки риска геморрагических осложнений, в частности HAS-BLED, АВС, HEMORR2HAGES, ATRIA, ORBIT, но расчетный высокий риск кровотечений не должен являться единственным и абсолютным ограничением к назначению АК. Несмотря на реально существующий риск развития кровотечений на фоне приема АК у пациентов с ФП, комплексный подход с учетом факторов риска не только тромбоэмболических, но и геморрагических осложнений, с акцентом на имеющиеся сопутствующие заболевания, наличие коморбидности, пожилой возраст и т.д., позволит индивидуально подходить к выбору АК и его дозы, способствуя оптимизации ведения такого рода пациентов.

Ключевые слова: фибрилляция предсердий, антикоагулянты, тромбоэмболические осложнения, кровотечение

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Atrial fibrillation (AF) is one of the most common types of cardiac arrhythmias, while AF is the main risk factor for ischemic stroke. For a long time, vitamin K antagonists, primarily warfarin, have been the standard for the prevention of thromboembolic complications in patients with AF. 5 years ago, dabigatran, rivaroxaban and apixaban occupied the 2nd place in the structure of anticoagulant prescribing (AC), giving way to warfarin. The well-known reason for the inadequate use of AC is the risk of bleeding. There are a large number of validated scales for assessing the risk of hemorrhagic complications, in particular HAS-BLED, ABC, HEMORRHR2HAGES, ATRIA, ORBIT, but the estimated high risk of bleeding should not be the only and absolute limitation to the appointment of AC. Despite the real risk of bleeding on the background of taking AC in patients with AF, an integrated approach taking into account not only the risk factors of the thromboembolic complications, but also hemorrhagic complications, with an emphasis on the existing comorbidities, the presence of comorbidity, old age, etc., will allow an individual approach to the choice of AC and its dose, contributing to the optimization of the management of such kind of patients.

Keywords: atrial fibrillation, anticoagulants, thromboembolic complications, bleeding

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Список литературы

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23. Roldan V, Marin F, Manzano-Fernandez S, et al. The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2013;62(23):2199-204. DOI:10.1016/j.jacc.2013.08.1623
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26. O'Brien EC, Simon DN, Thomas LE, et al. The ORBIT Bleeding Score: A Simple Bedside Score to Assess Bleeding Risk in Atrial Fibrillation. Eur Heart J. 2015;36(46):3258-64. DOI:10.1093/eurheartj/ehv476
27. Svennberg E, Engdahl J, Al-Khalili F, et al. Mass Screening for Untreated Atrial Fibrillation: The STROKESTOP Study. Circulation. 2015;131(25):2176-84.
DOI:10.1161/CIRCULATIONANA.114.014343
28. McMurray JJV, Ezekowitz JA, Lewis BS, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail. 2013;6(3):451-60. DOI:10.1161/CIRCHEARTFAILURE.112.000143
29. Lopes RD, Alexander JH, Al-Khatib SM, et al. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159(3):331-9. DOI:10.1016/j.ahj.2009.07.035
30. Graham DJ, Baro E, Zhang R, et al. Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation. Am J Med. 2019;132(5):596-604.e11. DOI:10.1016/j.amjmed.2018.12.023
31. Ferreira J, Ezekowitz MD, Connolly SJ, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail. 2013;15(9):1053-61. DOI:10.1093/eurjhf/hft111
32. Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol. 2014;63:2141-7. DOI:10.1016/j.jacc.2014.02.549
33. Miller CS, Dorreen A, Martel M, et al. Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2017;15(11):1674-83. DOI:10.1016/j.cgh.2017.04.031
34. Wehling M, Collins R, Gil VM, et al. Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016). Drugs Aging. 2017;34(7):499-507. DOI:10.1007/s40266-017-0466-6
35. Pollack CV. Coagulation assessment with the new generation of oral anticoagulants. Emerg Med J. 2016;33:423-30. DOI:10.1136/emermed-2015-204891
36. Kotecha D, Chudasama R, Lane DA, et al. Atrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic reviewand metaanalysis of death and adverse outcomes. Int J Cardiol. 2016;203:660-6.
37. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implicationsfor the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol. 2014;64:2222-31. DOI:10.1016/j.jacc.2014.09.028

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1. Jonas DE, Kahwati LC, Yun JY, et al. Screening for Atrial Fibrillation With Electrocardiography: An Evidence Review for the US Preventive Services Task Force: Evidence Synthesis No. 164. Rockville, MD: Agency for Healthcare Research and Quality, 2018. AHRQ publication 17-05236-EF-1.
2. Centers for Disease Control and Prevention (CDC). Atrial fibrillation fact sheet. CDC website. Available at: https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm. Updated August 22, 2017. Accessed: 21.06.2018.
3. Kato E, Ngo-Metzger Q, Fingar KR, et al. Statistical Brief 236: Inpatient Stays Involving Atrial Fibrillation, 1998–2014. Healthcare Cost and Utilization Project website. Available at: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb236-Atrial-Fibrillation-Hospital-Stays-Trends.jsp. Published February 2018. Accessed: 21.06.2018.
4. Screening for Atrial Fibrillation With Electrocardiography US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force Article Information. JAMA. 2018;320(5):478-84. DOI:10.1001/jama.2018.10321
5. Morillo CA, Banerjee A, Perel P, et al. Atrial fibrillation: the current epidemic. J Geriatr Cardiol. 2017;14(3):195-203. DOI:10.11909/j.issn.1671-5411.2017.03.011
6. Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021;23(10):1612-76. DOI:10.1093/europace/euab065
7. 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
8. Petrov VI, Shatalova OV, Maslakov AS. Analysis of antithrombotic therapy in patients with permanent atrial fibrillation (pharmacoepidemiological study). Rational Pharmacotherapy in Cardiology. 2014;10(2):174-8 (in Russian).
9. Singer DE, Hellkamp AS, Piccini JP, et al. Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. J Am Heart Assoc. 2013;2(1):e000067. DOI:10.1161/JAHA.112.000067
10. Vestergaard AS, Skjøth F, Larsen TB, et al. The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis. PLoS One. 2017;12(11):e0188482. DOI:10.1371/journal.pone.0188482
11. Liu S, Li X, Shi Q, et al. Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation. Curr Med Res Opin. 2018;34(3):415-21. DOI:10.1080/03007995.2017.1384370
12. Liu S, Singer A, McAlister FA, et al. Quality of warfarin management in primary care: Determining the stability of international normalized ratios using a nationally representative prospective cohort. Can Fam Physician. 2019;65:416-25.
13. Apostolakis S, Sullivan RM, Olshansky B, Lip GYH. Factors affecting quality of anticoagulation control amongst atrial fibrillation patients on warfarin: the SAMe-TT2R2 score. Chest. 2013;144(5):1555-63. DOI:10.1378/chest.13-0054
14. Диагностика и лечение фибрилляции предсердий. Российские рекомендации. 2011. Рациональная фармакотерапия в кардиологии. 2011;7(4):5-80 [Diagnosis and treatment of atrial fibrillation. Russian guidelines. 2011. Rational Pharmacotherapy in Cardiology. 2011;7(4):5-80 (in Russian)]. DOI:10.20996/1819-6446-2011-7-4
15. Sindet-Pedersen C, Lamberts M, Staerk L, et al. Combining Oral Anticoagulants With Platelet Inhibitors in Patients With Atrial Fibrillation and Coronary Disease. J Am Coll Cardiol. 2018;72:1790-800. DOI:10.1016/j.jacc.2018.07.054
16. Gaisenok OV, Leonov AS. The use of oral anticoagulants in patients with atrial fibrillation: cohort study data. Rational Pharmacotherapy in Cardiology. 2016;12(4):376-79 (in Russian). DOI:10.20996/1819-6446-2016-12-4-376-379
17. O'Brien EC, Simon DN, Allen LA, et al. Reasons for Warfarin Discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J. 2014;68(4):487-94. DOI:10.1016/j.ahj.2014.07.002
18. Mazurek M, Halperin JL, Huisman MV, et al. Antithrombotic treatment for newly diagnosed atrial fibrillation in relation to patient age the GLORIA_AF registry programme. Europace. 2020;22(1):47-57. DOI:10.1093/europace/euz278
19. Ionin VA, Barashkova EI, Filatova AG, et al. Atrial fibrillation in St Petersburg cohort: frequency, risk factors, antiarrhythmic therapy and thromboembolism prevention. Arterial’naya Gipertenziya (Arterial Hypertension). 2020;26(2):192-201 (in Russian). DOI:10.18705/1607-419X-2020-26-2-192-201
20. Turakhia MP, Shafrin J, Bognar K, et al. Estimated prevalence of undiagnosed atrial fibrillation in the United States. PLoS One. 2018;13:e0195088. DOI:10.1371/journal.pone.0195088
21. Petrov VI, Shatalova OV, Gerasimenko AS, Gorbatenko VS. Comparative Analysis of Antithrombotic Therapy in In-Patients with Atrial Fibrillation. Rational Pharmacotherapy in Cardiology. 2019;15(1):49-53 (in Russian). DOI:10.20996/1819-6446-2019-15-1-49-53
22. Hijazi Z, Oldgren J, Lindback J, et al. ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016;387:2302-11. DOI:10.1016/S0140-6736(16)00741-8
23. Roldan V, Marin F, Manzano-Fernandez S, et al. The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2013;62(23):2199-204. DOI:10.1016/j.jacc.2013.08.1623
24. Panchenko EP. Antitromboticheskaia terapiia v kardiologii. Moscow: Remedium, 2019 (in Russian).
25. Hijazi Z, Oldgren J, Lindbäck J, et al. ARISTOTLE and RE-LY Investigators The Novel BiomarkerBased ABC (Age, Biomarkers, Clinical History)-Bleeding Risk Score for Patients 140 With Atrial Fibrillation: A Derivation and Validation Study. Lancet. 2016;387(10035):2302-11. DOI:10.1016/S0140- 6736(16)00741-8
26. O'Brien EC, Simon DN, Thomas LE, et al. The ORBIT Bleeding Score: A Simple Bedside Score to Assess Bleeding Risk in Atrial Fibrillation. Eur Heart J. 2015;36(46):3258-64. DOI:10.1093/eurheartj/ehv476
27. Svennberg E, Engdahl J, Al-Khalili F, et al. Mass Screening for Untreated Atrial Fibrillation: The STROKESTOP Study. Circulation. 2015;131(25):2176-84.
DOI:10.1161/CIRCULATIONANA.114.014343
28. McMurray JJV, Ezekowitz JA, Lewis BS, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail. 2013;6(3):451-60. DOI:10.1161/CIRCHEARTFAILURE.112.000143
29. Lopes RD, Alexander JH, Al-Khatib SM, et al. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159(3):331-9. DOI:10.1016/j.ahj.2009.07.035
30. Graham DJ, Baro E, Zhang R, et al. Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation. Am J Med. 2019;132(5):596-604.e11. DOI:10.1016/j.amjmed.2018.12.023
31. Ferreira J, Ezekowitz MD, Connolly SJ, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail. 2013;15(9):1053-61. DOI:10.1093/eurjhf/hft111
32. Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol. 2014;63:2141-7. DOI:10.1016/j.jacc.2014.02.549
33. Miller CS, Dorreen A, Martel M, et al. Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2017;15(11):1674-83. DOI:10.1016/j.cgh.2017.04.031
34. Wehling M, Collins R, Gil VM, et al. Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016). Drugs Aging. 2017;34(7):499-507. DOI:10.1007/s40266-017-0466-6
35. Pollack CV. Coagulation assessment with the new generation of oral anticoagulants. Emerg Med J. 2016;33:423-30. DOI:10.1136/emermed-2015-204891
36. Kotecha D, Chudasama R, Lane DA, et al. Atrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic reviewand metaanalysis of death and adverse outcomes. Int J Cardiol. 2016;203:660-6.
37. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implicationsfor the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol. 2014;64:2222-31. DOI:10.1016/j.jacc.2014.09.028

Авторы

С.А. Бернс*1, О.Л. Барбараш2

1 ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава России, Москва, Россия;
2 ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Россия
*svberns@yandex.ru

________________________________________________

Svetlana A. Berns*1, Olga L. Barbarash2

1 National Research Center for Therapy and Preventive Medicine, Moscow, Russia;
2 Research Institute of Complex Problems of Cardiovascular Diseases, Kemerovo, Russia
*svberns@yandex.ru

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