Сложные вопросы антитромботической терапии при остром коронарном синдроме у пациентов с фибрилляцией предсердий

А.С. Рудой, Ю.С. Лысый

УО «Белорусский государственный медицинский университет», ГУ «432 ордена Красной Звезды главный военный клинический медицинский центр Вооруженных Сил Республики Беларусь»

Вопросы выбора антикоагулянта, количества антиагрегантов и длительности антитромботической терапии у пациентов с острым коронарным синдромом, имеющим показания к приему оральных антикоагулянтов, в частности при фибрилляции предсердий, остаются сложными и неоднозначными. С одной стороны, развитие острого коронарного синдрома требует назначения двойной антиагрегантной терапии, с другой, совместный прием антикоагулянта и антиагрегантов значительно повышает геморрагические риски. Складывается клиническая ситуация, когда необходимы четкие знания в стратегии и выборе антитромботических препаратов – соблюдении баланса между риском развития тромбоза стента, тромбоэмболическими и геморрагическими осложнениями. В представленном обзоре систематизированы данные, касающиеся режима антитромботической терапии, при различных видах острого коронарного синдрома у пациентов с фибрилляцией предсердий в зависимости от выбора тактики лечения (фармако-инвазивной, либо консервативной).

ключевые слова: острый коронарный синдром (ОКС), фибрилляции предсердий, антиагреганты, новые пероральные антикоагулянты, не являющиеся антагонистами витамина К (НОАК), двойная антитромбоцитарная терапия (ДАТТ), ишемические события, кровотечения, чрезкожное коронарное вмешательство (ЧКВ)

для цитирования: А.С. Рудой, Ю.С. Лысый. Сложные вопросы антитромботической терапии при остром коронарном синдроме у пациентов с фибрилляцией предсердий. Неотложная кардиология и кардиооваскулярные риски, 2019, Т. 3, № 1, С. 474–488

Complex problems of antithrombotic therapy for acute coronary syndrome in patients with atrial fibrillation

A.S. Rudoy, Yu.S. Lysyy

The choice of anticoagulant, the number of antiplatelet agents and the duration of antithrombotic therapy in patients with acute coronary syndrome with indications for oral anticoagulants, in particular for atrial fibrillation, remain complex and ambiguous. On the one hand, the development of acute coronary syndrome requires the appointment of dual antiplatelet therapy, on the other, the combined use of anticoagulant and antiaggregants significantly increases hemorrhagic risks. There is a clinical situation, when you need a clear knowledge of the strategy and choice of antithrombotic drugs, in particular the knowledge about the balance between the risk of developing stent thrombosis, thromboembolic and hemorrhagic complications. In the presented review, the data concerning the regime of antithrombotic therapy are systematized in various types of acute coronary syndrome in patients with atrial fibrillation, depending on the choice of treatment tactics (pharmaco-invasive or conservative).

keywords: acute coronary syndrome (ACS), atrial fibrillation, antiplatelet agents, oral anticoagulants, non-vitamin K antagonist oral anticoagulant (NOAC), double antiplatelet therapy (DAPT), ischemic events, bleeding, percutaneous coronary intervention (PCI)

for references: A.S. Rudoy, Yu.S. Lysyy. Complex problems of antithrombotic therapy for acute coronary syndrom in patients with atrial fibrillation. Neotlozhnaya kardiologiya i kardioovaskulyarnye riski [Emergency cardiology and cardiovascular risks], 2019, vol. 3, no. 1, pp. 474–488

1. Ruiz-Nodar J.M., Marín F., Hurtado J.A., Valencia J., Pinar E., Pineda J., Gimeno J.R., Sogorb F., Valdés M., Lip G.Y. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation: implications for bleeding risk and prognosis. J Am Coll Cardiology, 2008, vol. 51, no. 8, pp. 818-825. doi: 10.1016/j.jacc.2007.11.035.
2. Hansen M.L., Sørensen R., Clausen M.T., Fog-Petersen M.L., Raunsø J., Gadsbøll N., Gislason G.H., Folke F., Andersen S.S., Schramm T.K., Abildstrøm S.Z., Poulsen H.E., Køber L., Torp-Pedersen C. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med, 2010, vol. 170, no. 16, pp. 1433-1441. doi: 10.1001/archinternmed.2010.271.
3. Lamberts M., Olesen J.B., Ruwald M.H., Hansen C.M., Karasoy D., Kristensen S.L., Køber L., Torp-Pedersen C., Gislason G.H., Hansen M.L. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation, 2013, vol. 127, no. 17, pp. e585. doi: 10.1161/CIRCULATIONAHA.112.114967.
4. Kolh P., Windecker S., Alfonso F., Collet J.P., Cremer J., Falk V., Filippatos G., Hamm C., Head S.J., Jüni P., Kappetein A.P., Kastrati A. 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 J Cardiothorac Surg, 2014, vol. 46, no. 4, pp. 517-592. doi: 10.1007/s12265-015-9632-6.
5. Gao X.F., Chen Y., Fan Z.G., Jiang XM1, Wang Z.M., Li B., Mao W.X., Zhang J.J., Chen S.l. Antithrombotic regimens for patients taking oral anticoagulation after coronary intervention: a meta-analysis of 16 clinical trials and 9185 patients. Clin Cardiol, 2015, vol. 38, no. 8, pp. 499-509. doi: 10.1002/clc.22411.
6. Dans A.L., Connolly S.J., Wallentin L., Yang S., Nakamya J., Brueckmann M., Ezekowitz M., Oldgren J., Eikelboom J.W., Reilly P.A., Yusuf S. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation, 2013, vol. 127, no. 5, pp. 634-640. doi: 10.1016/j.jacc.2018.04.063.
7. Vandvik P.O., Lincoff A.M., Gore J.M., Gutterman D.D., Sonnenberg F.A., Alonso-Coello P., Akl E.A., Lansberg M.G., Guyatt G.H., Spencer F.A. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2012, vol. 141, no. 2, pp. e637S-e668S. doi: 10.1378/chest.11-2306.
8. Rubboli A., Faxon D.P., Juhani Airaksinen K.E., Schlitt A., Marín F., Bhatt D.L., Lip G.Y. The optimal management of patients on oral anticoagulation undergoing coronary artery stenting. Thromb Haemost, 2014, vol. 112, no. 6, pp. 1080-1087. doi: 10.1160/TH14-08-0681.
9. Oldgren J., Wallentin L., Alexander J.H., James S., Jönelid B., Steg G., Sundström J. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J, 2013, vol. 34, no. 22, pp. 1670-1680. doi: 10.1093/eurheartj/eht049.
10. Kolh P., Windecker S., Alfonso F., Collet J.P., Cremer J., Falk V., Filippatos G., Hamm C., Head S.J., Jüni P., Kappetein A.P., Kastrati A. et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the Europe an 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 J Cardiothorac Surg, 2014, vol. 46, no. 4, pp. 517-592. doi: 10.1007/s12265-015-9632-6.
11. Roffi M., Patrono C., Collet J.P., Mueller C., Valgimigli M., Andreotti F., Bax J.J., Borger M.A., Brotons C., Chew D.P., Gencer B., Hasenfuss G., Kjeldsen K., Lancellotti P., Landmesser U., Mehilli J., Mukherjee D., Storey R.F., Windecker S. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Kardiol Pol, 2015, vol. 73, no. 12, pp. 1207-1294. doi:10.1161/CIRCULATIONAHA. 116.026418.
12. Kirchhof P., Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B., Castellá M., Diener H.C., Heidbuchel H., Hendriks J., Hindricks G., Manolis A.S., Oldgren J., Alexandru Popescu B., Schotten U., Van Putte B., Vardas P. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Rev Esp Cardiol (Engl Ed), 2016, vol. 37. no. 38, pp. 2893-2962. doi: 10.1016/j.rec.2017.07.009.
13. Gorenek B., Pelliccia A., Benjamin E.J., Boriani G., Crijns H.J., Fogel R.I., Van Gelder I.C., Halle M., Kudaiberdieva G., Lane D.A. et al. European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS). Europace, 2017, vol. 19, no. 2, pp. 190-225. doi: 10.1093/europace/euw242.
14. Ibanez B., James S., Agewall S., Antunes M.J., Bucciarelli-Ducci C., Bueno H., Caforio A.L.P., Crea F., Goudevenos J.A., Halvorsen S., Hindricks G., Kastrati A., Lenzen M.J., Prescott E., Roffi M., Valgimigli M., Varenhorst C., Vranckx P., Widimský P. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J, 2017, vol. 39, no. 2, pp. 119-177. doi: 10.1093/eurheartj/ehx393.
15. Pisters R., Lane D.A., Nieuwlaat R., De Vos C.B., Crijns H.J., Lip G.Y. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest, 2010, vol. 138, no. 5, pp. 1093-1100.doi: 10.1378/chest.10-0134.
16. Hijazi Z., Oldgren J., Lindbäck J., Alexander J.H., Connolly S.J., Eikelboom J.W., Ezekowitz M.D., Held C., Hylek E.M., Lopes R.D., Siegbahn A., Yusuf S5, Granger C.B., Wallentin L. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet, 2016, vol. 387, no. 10035, pp. 2302-2311. doi: 10.1016/S0140-6736(16)00741-8.
17. Bach R.G., Cannon C.P., Weintraub W.S., Dibattiste P.M., Demopoulos L.A., Anderson H.V., DeLucca P.T., Mahoney E.M., Murphy S.A., Braunwald E. The effect of routine, early invasive management on outcome for elderly patients with non–ST-segment elevation acute coronary syndromes. Ann Intern Med, 2004, vol. 141, no. 3, pp. 186-195. doi: 10.7326/0003-4819-141-3-200408030-00007.
18. Rosengren A., Wallentin L., K Gitt A., Behar S., Battler A., Hasdai D.M. Sex, age, and clinical presentation of acute coronary syndromes. Eur Heart J, 2004, vol. 25, no. 8, pp. 663-670. doi: 10.1016/j.ehj.2004.02.023.
19. Alfredsson J., Stenestrand U., Wallentin L., Swahn E. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome. Heart, 2007, vol. 93, no. 11, pp. 1357-1362. doi: 10.1136/hrt.2006.102012.
20. White H.D., Ohman E.M., Lincoff A.M., Bertrand M.E., Colombo A., McLaurin B.T., Cox D.A., Pocock S.J., Ware J.A., Manoukian S.V., Lansky A.J., Mehran R., Moses J.W., Stone G.W. Safety and efficacy of bivalirudin with and without glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: 1-year results from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. J Am College Cardiology, 2008, vol. 52, no. 10, pp. 807-814. doi: 10.1016/j.jacc.2008.05.036.
21. Lincoff A.M., Steinhubl S.R., Manoukian S.V., Chew D., Pollack C.V. Jr., Feit F., Ware J.H., Bertrand M.E., Ohman E.M., Desmet W., Cox D.A., Mehran R., Stone G.W. Influence of timing of clopidogrel treatment on the efficacy and safety of bivalirudin in patients with non–ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention: an analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. JACC Cardiovasc Interv, 2008, vol. 1, no. 6, pp. 639-648. doi: 10.1016/j.jcin.2008.10.004
22. O’Donoghue M., Antman E.M., Braunwald E., Murphy S.A., Steg P.G., Finkelstein A., Penny W.F., Fridrich V., McCabe C.H., Sabatine M.S., Wiviott S.D. The efficacy and safety of prasugrel with and without a glycoprotein iib/iiia inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) Analysis. J Am Coll Cardiol, 2009, vol. 54, no. 8, pp. 678-685. doi : 10.1016/j.jacc.2009.05.025.
23. Buller C.E., Pate G.E., Armstrong P.W., O’Neill B.J., Webb J.G., Gallo R., Welsh R.C. Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment. Can J Cardiol, 2006, vol. 22, no. 6, pp. 511-515. doi: 10.1016/S0828-282X(06)70271-9.
24. Jolly S.S., Faxon D.P., Fox K.A., Afzal R., Boden W.E., Widimsky P., Steg P.G., Valentin V., Budaj A., Granger C.B., Joyner C.D., Chrolavicius S., Yusuf S., Mehta S.R. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol, 2009, vol. 54, no. 5, pp. 468-476. doi:10.1016/j.jacc.2009.03.062.
25. Lopes R.D., Alexander K.P., Marcucci G., White H.D., Spinler S., Col J., Aylward P.E., Califf R.M., Mahaffey K.W. Outcomes in elderly patients with acute coronary syndromes randomized to enoxaparin vs. unfractionated heparin: results from the SYNERGY trial. Eur Heart J, 2008, vol. 29, no. 15, pp. 1827-1833. doi: 10.1093/eurheartj/ehn236.
26. Wallentin L., Lagerqvist B., Husted S., Kontny F., Ståhle E., Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. Lancet, 2000, vol. 356, no. 9223, pp. 9-16. doi: 10.1159/000054175.
27. Lagerqvist B., Husted S., Kontny F., Ståhle E., Swahn E., Wallentin L. 5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study. Lancet, 2006, vol. 368, no. 9540, pp. 998-1004. doi: 10.1016/S0140-6736(06)69416-6.
28. Diercks D.B., Owen K.P., Kontos M.C., Blomkalns A., Chen A.Y., Miller C., Wiviott S., Peterson E.D. Gender differences in time to presentation for myocardial infarction before and after a national women’s cardiovascular awareness campaign: A temporal analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation (CRUSADE) and the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (NCDR ACTION Registry–GWTG). Am Heart J, 2010, vol. 160, no. 1, pp. 80-87. e3. doi:10.1016/j.ahj.2010.04.017.
29. Hvelplund A., Galatius S., Madsen M, Rasmussen J.N., Rasmussen S., Madsen J.K., Sand N.P., Tilsted H.H., Thayssen P., Sindby E., Højbjerg S., Abildstrøm S.Z. Women with acute coronary syndrome are less invasively examined and subsequently less treated than men. Eur Heart J, 2009, vol. 31, no. 6, pp. 684-690. doi: 10.1093/eurheartj/ehp493.
30. Dewilde W.J., Oirbans T., Verheugt F.W., Kelder J.C., De Smet B.J., Herrman J.P., Adriaenssens T., Vrolix M., Heestermans A.A., Vis M.M., Tijsen J.G., van ‘t Hof A.W., ten Berg J.M. 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, vol. 381, no. 9872, pp. 1107-1115. doi: 10.1016/S0140-6736(12)62177-1.
31. Gibson C.M., Mehran R., Bode C., Halperin J., Verheugt F., Wildgoose P., van Eickels M., Lip G.Y., Cohen M., Husted S., Peterson E., Fox K. 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, vol. 169, no. 4, pp. 472-478. e5. doi: 10.1016/j.ahj.2014.12.006.
32. Cannon C.P., Bhatt D.L., Oldgren J., Lip G.Y.H., Ellis S.G., Kimura T., Maeng M., Merkely B., Zeymer U., Gropper S., Nordaby M., Kleine E., Harper R., Manassie J., Januzzi J.L., Ten Berg J.M., Steg P.G., Hohnloser S.H. Dual antithrombotic therapy with dabigatran af ter PCI in atrial fibrillation. N Engl J Med, 2017, vol. 377, no. 16, pp. 1513-1524. doi: 10.1056/NEJMoa1708454.
33. Vranckx P., Lewalter T., Valgimigli M., Tijssen J.G., Reimitz P.E., Eckardt L., Lanz H.J., Zierhut W., Smolnik R., Goette A. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: rationale and design of the ENTRUST-AF PCI trial. Am Heart J, 2018, vol. 196, pp. 105-112. doi: 10.1016/j.ahj.2017.10.009.
34. Neumann F.J., Sousa-Uva M., Ahlsson A., Alfonso F., Banning A.P., Benedetto U., Byrne R.A., Collet J.P., Falk V., Head S.J., Jüni P., Kastrati A. Koller A., Kristensen S.D., Niebauer J., Richter D.J., Seferovic P.M., Sibbing D., Stefanini G.G., Windecker S., Yadav R., Zembala M.O. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J, 2018, no. 25. https://doi.org/10.1093/eurheartj/ehy394.

Полнотекстовая статья

Скачать статью

Формат файла: pdf (381.34 Кб)

→ Главная → 2019 том 3, №1