Некоторые аспекты применения антикоагулянтов при венозных тромбоэмболиях, тромбоэмболии легочной артерии. Фокус на пожилых пациентов

Pаспространенность венозных тромбоэмболий (ВТЭ), а также смертность от данной патологии среди населения во всем мире занимает лидирующие позиции. Частота встречаемости, а также степень тяжести ВТЭ тем больше, чем старше пациент. Появление новой группы прямых оральных антикоагулянтов внесло существенные коррективы в схемы ведения данных групп пациентов. В статье затронута проблема выбора, эффективности и безопасности применения пероральных антикоагулянтов у пациентов пожилого и старческого возраста при ВТЭ, в частности, при тромбоэмболии легочной артерии (ТЭЛА). Приводится анализ результатов рандомизированных клинических исследований и проспективных когортных наблюдений; даются рациональные, по мнению авторов, рекомендации по оптимальному выбору перорального антикоагулянта у данных категорий пациентов. Апиксабан и ривароксабан являются высокоэффективными препаратами выбора с надежным профилем безопасности у пациентов старческой возрастной группы при профилактике и лечении ВТЭ, включая ТЭЛА, а апиксабан имеет оптимальный профиль и класс безопасности — А, согласно мнению экспертов FORTA, среди всех остальных пероральных антикоагулянтов при применении у пациентов пожилого и старческого возраста.

1. Mazzolai L, Aboyans V, Ageno W, et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J. 2018;39(47):4208-4218. doi:10.1093/eurheartj/ehx003.

2. Wendelboe AM, Raskob GE. Global burden of thrombosis: epidemiologic aspects. Circ Res. 2016;118(9):1340-7. doi:10.1161/CIRCRESAHA.115.306841.

3. Barco S, Cheung YW, Eikelboom JW, et al. New oral anticoagulants in elderly patients. Best Pract Res Clin Haematol. 2013;26:215-24. doi:10.1016/j.beha.2013.07.011.

4. Stein PD, Hull RD, Kayali F, et al. Venous thromboembolism according to age: The impact of an aging population. Archives of Internal Medicine. 2004;164(20):2260-5. doi:10.1001/archinte.164.20.2260.

5. Heit JA, Spencer FA, White RH, et al. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41:3-14. doi:10.1007/s11239-015-1311-6.

6. Laporte S, Mismetti P, Décousus H, et al. Clinical predictors for fatal pulmonary embolism in 15 520 patients with venous thromboembolism: Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry. Circulation. 2008;117(13):1711-6.

7. Bauersachs RM. Use of anticoagulants in elderly patients. Thromb. Res. 2012;129(2):107- 15. doi:10.1016/j.thromres.2011.09.013.

8. Prandoni P. Major bleeding as a predictor of mortality in patients with venous thromboembolism: Findings from the RIETE Registry. J. Thromb. Haemost. 2010;8(11):2575-7. doi:10.1111/j.1538-7836.2010.04039.x.

9. Van der Hulle T, Kooiman J, Den Exter PL, et al. Effectiveness and safety of novel oral anticoagulants 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:10.1111/jth.12485.

10. Wattanakit K, Lutsey PL, Bell EJ, et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost. 2012;108(3):508-15. doi:10.1160/TH11-10-0726.

11. Enga KF, Braekkan SK, Hansen-Krone IJ, et al. Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study. J Thromb Haemost. 2012;10(10):2068-74. doi:10.1111/j.1538-7836.2012.04880.x.

12. Sørensen HT, Horvath-Puho E, Lash TL, et al. Heart disease may be a risk factor for pulmonary embolism without peripheral deep venous thrombosis. Circulation 2011;124(13):1435-41. doi:10.1161/CIRCULATIONAHA.111.025627.

13. Prandoni P, Pesavento R, Sørensen HT, et al. Prevalence of heart diseases in patients with pulmonary embolism with and without peripheral venous thrombosis: findings from a cross-sectional survey. Eur J Intern Med. 2009;20(5):470-3. doi:10.1016/j.ejim.2009.06.001.

14. Ortel ThL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-738. doi:10.1182/bloodadvances.2020001830.

15. Coutance G, Cauderlier E, Ehtisham J, et al. The prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis. Crit Care. 2011;15(2):R103. doi:10.1186/cc10119.

16. Jiménez D, Aujesky D, Moores L, et al. Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism. Thorax. 2011;66(1):75-8. doi:10.1136/thx.2010.150656.

17. Jiménez D, Lobo JL, Barrios D, et al. Risk stratification of patients with acute symptomatic pulmonary embolism. Intern. Emerg. Med. 2016;11(1):11-8. doi:10.1007/s11739-015-1388-0.

18. Cossette B, Pelletier ME, Carrier N, et al. Evaluation of bleeding risk in patients exposed to therapeutic unfractionated or low-molecular-weight heparin: a cohort study in the context of a quality improvement initiative. Ann Pharmacother. 2010;44:994-1002.

19. Erkens PM, Prins MH. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2010;9:CD001100. doi:10.1002/14651858.CD001100.pub3.

20. Stein PD, Hull RD, Matta F, et al. Incidence of thrombocytopenia in hospitalized patients with venous thromboembolism. Am J Med. 2009;122:919-30.

21. Prandoni P, Siragusa S, Girolami B, et al. BELZONI Investigators Group. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecularweight heparin: a prospective cohort study. Blood. 2005;106:3049-54.

22. Meyer G, Vicaut E, Danays T, et al. PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:1402-11.

23. Zondag W, Mos IC, Creemers-Schild D, et al. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011;9:1500-7.

24. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, openlabel, randomised, non-inferiority trial. Lancet. 2011;378(9785):41-8. doi:10.1016/S0140-6736(11)60824-6.

25. Blann AD, Lip GYH. Non-Vitamin K antagonist oral anticoagulants (NOACs) for the management of venous thromboembolism. Heart. 2016;102(12):975-83.

26. Gómez-Outes A. Direct-acting oral anticoagulants: Pharmacology, indications, management, and future perspectives. Eur. J. Haematol. 2015;95(5):389-404. doi:10.1111/ejh.12610.

27. Hirschl M, Kundi M. New oral anticoagulants in the treatment of acute venous thromboembolism — a systematic review with indirect comparisons. Vasa. 2014;43(5):353- 64. doi:10.1024/0301-1526/a000373.

28. Finks SW. Management of Venous Thromboembolism: Recent Advances in Oral Anticoagulation Therapy. Ann. Pharmacother. 2016;50(6):486-501.

29. Agnelli G, Buller HR, Cohen A, et al. AMPLIFY investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799-808. doi:10.1056/NEJMoa1302507.

30. Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287-97. doi:10.1056/NEJMoa1113572.

31. Prins MH, Lensing AW, Bauersachs R, et al. EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11:21. doi:10.1186/1477-9560-11-21.

32. Schulman S, Kakkar AK, Goldhaber SZ, et al. RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129:764-72. doi:10.1161/CIRCULATIONAHA.113.004450.

33. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-52. doi:10.1056/NEJMoa0906598.

34. Schulman S, Eriksson H, Goldhaber SZ, et al. Influence of age on the efficacy and safety of dabigatran versus warfarin for the treatment of acute venous thromboembolism: a pooled analysis of RE-COVER and RECOVER II. Blood. 2013;122:2375.

35. Buller HR, Decousus H, Grosso MA, et al. Hokusai VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406-15. doi:10.1056/NEJMoa1306638.

36. Agnelli G, Buller HR, Cohen A, et al.; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708. doi:10.1056/NEJMoa1207541.

37. Alotaibi G, Alsaleh K, Wu C, et al. Dabigatran, rivaroxaban and apixaban for extended venous thromboembolism treatment: network meta-analysis. Int Angiol. 2014;33(4):301-8.

38. Weitz JI, Lensing AW, Prins MH, et al. for the EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376(13):1211-22. doi:10.1056/NEJMoa1700518.

39. Schulman S, Kearon C, Kakkar AK, et al, RE-MEDY Trial Investigators, RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709-18.

40. Geldhof V, Vandenbriele C, Verhamme P, et al. Venous thromboembolism in the elderly: Efficacy and safety of non-VKA oral anticoagulants. Thromb J. 2014;12:21. doi:10.1186/1477-9560-12-21.

41. Trujillo-Santos J, Beroiz P, Moustafa F, et al.; RIETE Investigators. Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism. Thromb Res. 2020;193:160-5. doi:10.1016/j.thromres.2020.06.035.

42. Wehling M, Burkhardt H, Kuhn-Thiel AM, et al. VALFORTA — a randomized trial to validate the FORTA (“Fit fOR The Aged”) classification. Age Ageing. 2016;45:262-7. doi:10.1093/ageing/afv200.