Подходы к выбору антикоагулянтной терапии у больных с неклапанной фибрилляцией предсердий и ишемической болезнью сердца

В статье представлены подходы к выбору антитромботической терапии (АТ) у больных неклапанной фибрилляцией предсердий (ФП) и ишемической болезнью сердца (ИБС) как при остром коронарном синдроме (ОКС), так и стабильных формах, в т.ч. у перенесших чрескожное коронарное вмешательство. Определение режимов и длительность АТ зависят от формы ИБС, риска кровотечений, анатомии имплантированных стентов в коронарных артериях. В составе АТ в современных регламентирующих документах больным ИБС и ФП рекомендуется любой оральный антикоагулянт: антагонисты витамина К, прямой ингибитор тромбина — дабигатран, селективные ингибиторы Xa фактора свертывания — ривароксабан, апиксабан. Наибольшая доказательная база среди новых оральных антикоагулянтов при данной клинической ситуации представлена для дабигатрана. Выбор двойного и тройного режимов АТ для больных ИБС и с ФП дискутируется. Среди антитромбоцитарных препаратов для комбинации с антикоагулянтом предпочтителен клопидогрел как более безопасный препарат в сравнении с аспирином. Возможность использования для комбинированной терапии с антикоагулянтами тикагрелора и прасугрела ограничена. Указывается на необходимость применения ингибиторов протонной помпы при назначении как двойной, так и тройной АТ больным с неклапанной ФП и ИБС. 

1. Lip GY, Laroche C, Dan GA, et al. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace 2014; 16(3): 308-19.

2. Kirchhof P, Ammentorp B, Darius H, et al. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events — European Registry in Atrial Fibrillation (PREFER in AF). Europace 2014; 16(1): 6-14.

3. Fauchier L, Greenlaw N, Ferrari R, et al. Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry. PLoS One 2015; 10(4): e0125164.

4. Bhatia GS, Lip GY. Atrial fibrillation post-myocardial infarction: frequency, consequences, and management.Curr Heart Fail Rep 2004; 1(4): 149-55.

5. Schmiegelow MD, Pedersen OD, Køber L, et al. Incidence of atrial fibrillation in patients with either heart failure or acute myocardial infarction and left ventricular dysfunction: a cohort study. BMC Cardiovasc Disord 2011; 11: 19.

6. Chamberlain AM, Gersh BJ, Mills RM, et al. Antithrombotic strategies and outcomes in acute coronary syndrome with atrial fibrillation. Am J Cardiol 2015; 115(8): 1042-8.

7. Braga CG, Ramos V, Martins J, et al. Impact of atrial fibrillation type during acute coronary syndromes: Clinical features and prognosis. Rev Port Cardiol 2015; 34(6): 403-10.

8. González-Pacheco H, Márquez MF, Arias-Mendoza A, et al. Clinical features and in￾hospital mortality associated with different types of atrial fibrillation in patients with acute coronary syndrome with and without ST elevation. J Cardiol 2015; 66(2): 148-54.

9. Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res 2014; 114(9): 1453-68.

10. Camm J, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology. Eur Heart J 2010; 31: 2369-429.

11. Diagnosis and treatment of atrial fibrillation. The recommendations of the RSC, VNOA, ASSH 2012. Russ J Cardiol 2013: 4 (102), Suppl. 3. Russian (Диагностика и лечение фибрилляции предсердий. Рекомендации РКО, ВНОА, ОССН. Российский кардиологический журнал 2013: 4 (102), приложение 3).

12. Fuster V, Rydén LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the ACC/AHA Task Force on Practice Guidelines developed in partnership with the ESC and in collaboration with the EHRA and the HRS. JACC 2011; 57(11): e101-98.

13. De Vecchis R, Cantatrione C, Mazzei D. Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent. J Clin Med Res 2016; 8(2): 153-61.

14. Liu J, Fan M, Zhao J, et al. Efficacy and safety of antithrombotic regimens after coronary intervention in patients on oral anticoagulation: Traditional and Bayesian meta-analysis of clinical trials. Int J Cardiol 2016; 205: 89-96.

15. Verheugt FW. Triple therapy for percutaneous coronary intervention in atrial fibrillation: standard of care, or a nightmare soon to end? J Thromb Haemost 2015; 13 Suppl 1: S332-5.

16. https://clinicaltrials.gov/ct2/show/NCT02164864?term=dabigatran&rank=59.

17. https://clinicaltrials.gov/ct2/show/NCT02415400?term=apixaban+and+PCI&rank=1.

18. Gibson CM, Mehran R, Bode C, et al. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Am Heart J 2015; 169(4): 472-8.e5.

19. https://clinicaltrials.gov/ct2/show/NCT01962545?term=edoxaban+and+PCI&rank=1.

20. Lip GY, Windecker S, Huber K, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the ESC Working Group on Thrombosis, EHRA, EAPC and ACCA endorsed by HRS and APHRS. Eur Heart J 2014; 35(45): 3155-79.

21. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37(3): 267-315.

22. Lozano I, Sanchez-Insa E, de Leiras SR, et al. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel. Am J Cardiol 2016; 117(3): 366-8.

23. Nicolau JC, Bhatt DL, Roe MT, et al. Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel and managed without revascularization: insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial. Am Heart J 2015; 170(4): 683-94.e3.

24. Sherwood MW, Melloni C, Jones WS, et al. Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review. J Am Heart Assoc 2015; 4(11). pii: e002245.

25. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17: 1467-507.

26. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35(37): 2541-619.

27. Steg PG, James SK, Atar, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) 1. Eur Heart J 2012; 33(20): 2569-619.

28. Rahman A, Latona J. New oral anticoagulants and perioperative management of anticoagulant/antiplatelet agents. Aust Fam Physician 2014; 43(12): 861-6.

29. Huber K, Bates ER, Valgimigli M, et al. Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold? Am Heart J 2014; 168(5): 611-21.

30. Thompson PL, Verheugt FW. Managing antithrombotic therapy in patients with both atrial fibrillation and coronary heart disease. Clin Ther 2014; 36(9): 1176-81.

31. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51.

32. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-91.

33. Granger C, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-92.

34. Dans A, Connolly SJ, Wallentin L, et al. Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial. Circulation 2013; 127: 634-40.

35. Sinnaeve PR, Van de Werf F. Do ingredients make the difference: finding the best cocktail of an anticoagulant with antiplatelets. Circulation. 2013; 127(5): 566-8.

36. Koziolova NA, Polyanskaya EA. The problem of selecting the antithrombotic therapy in patients with non-valvular atrial fibrillation and co-morbid disease. Cardiovascular Therapy and Prevention 2015; 14(4): 75-85. Russian (Козиолова Н. А., Полянская Е.А. Проблемы выбора антитромботической терапии у больных неклапанной фибрилляцией предсердий и коморбидной патологией. Кардиоваскулярная терапия и профилактика 2015; 14(4): 75-85).

37. Gao F, Zhou YJ, Wang ZJ, et al. Meta-analysis of the combination of warfarin and dual antiplatelet therapy after coronary stenting in patients with indications for chronic oral anticoagulation. Int J Cardiol 2011; 148: 96-101.

38. Zhao HJ, Zheng ZT, Wang ZH, et al. “Triple therapy” rather than “triple threat”: a meta-analysis of the two antithrombotic regimens after stent implantation in patients receiving long-term oral anticoagulant treatment. Chest 2011; 139: 260-70.

39. Rubboli A. The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: facts and questions. J Geriatr Cardiol 2011; 8: 207-14.

40. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to ADP associated with ischemia and bleeding. JACC 2013; 62: 2261-73.

41. Lip GY, Huber K, Andreotti F, et al. European Society of Cardiology Working Group on Thrombosis.Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Thromb Haemost 2010; 103: 1328.

42. Faxon DP, Eikelboom JW, Berger PB, et al. Consensus document: antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting. A North￾American perspective. Thromb Haemost 2011; 106: 572-84.

43. Dewilde WJ, Oirbans T, Verheugt FW, et al. WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381: 1107-15.

44. Lamberts M, Gislason GH, Olesen JB, et al. Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention. JACС 2013; 62: 981-9.

45. De Vecchis R, Cantatrione C, Mazzei D. Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent. J Clin Med Res 2016; 8(2): 153-61.

46. Lopes RD, Rao M, Simon DN, et al. Triple Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease. Am J Med 2016; pii: S0002-9343(16)30025-0.

47. Beitelshees AL, Voora D, Lewis JP. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics. Pharmgenomics Pers Med 2015; 8: 43-61.

48. Mega JL, Simon T. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments. Lancet 2015; 386(9990): 281-91.

49. Clemens A, Fraessdorf M, Friedman J. Cardiovascular outcomes during treatment with dabigatran: comprehensive analysis of individual subject data by treatment. Vasc Health Risk Manag 2013; 9: 599-615.

50. Graham D, Reichman ME, Wernecke M, et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation 2015;131(2):157-64.

51. Villines TC, Schnee J, Fraeman K, et al. A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost 2015; 114(6): 1290-8.

52. Larsen TB, Rasmussen LH, Skj th F, et al. Efficacy and safety of Dabigatran etexilate and warfarin in”real-world” patients with atrial fibrillation: aprospective nationwide cohort study. JACC 2013; 61(22): 2264-73.

53. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123(21): 2363-72.