rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2022-08-09rpcardio-2795Research ArticleNOTES FROM PRACTICEКЛИНИЧЕСКИЙ ОПЫТPrevention of Cardioembolic Complications in Patients with Atrial Fibrillation: Efficacy and Safety of Left Atrial Appendage Isolation and Oral AnticoagulantsПрофилактика кардиоэмболических осложнений у пациентов с фибрилляцией предсердий: сопоставление эффективности и безопасности эндоваскулярной изоляции ушка левого предсердия и оральных антикоагулянтовhttps://orcid.org/0000-0002-5290-0065ПевзнерД. В.PevznerD. V.

Певзнер Дмитрий Вольфович.

Москва.

eLibrary SPIN 9982-5926

Dmitry V. Pevzner.

Moscow.

eLibrary SPIN 9982-5926

https://orcid.org/0000-0002-8746-8727КострицаН. С.KostritcaN. S.

Кострица Наталья Сергеевна.

Москва.

eLibrary SPIN 9540-0177

Natalia S. Kostritca.

Moscow.

eLibrary SPIN 9540-0177 

nataliakostritsaffm@gmail.comhttps://orcid.org/0000-0002-9842-0905АлиеваА. К.AlievaA. K.

Алиева Амина Кязымовна.

Москва.

Amina A. Alieva.

Moscow.

https://orcid.org/0000-0001-7461-3422МеркуловаИ. A.MerkulovaI. A.

Меркулова Ирина Алексеевна.

Москва.

eLibrary SPIN 6169-1588

Irina A. Merkulova.

Moscow.

eLibrary SPIN 6169-1588

https://orcid.org/0000-0003-2816-1183ЯвеловИ. С.YavelovI. S.

Явелов Игорь Семенович.

Москва.

eLibrary SPIN 7248-9323

Igor S. Yavelov.

Moscow.

eLibrary SPIN 7248-9323

https://orcid.org/0000-0001-8193-8575МеркуловЕ. В.MerkulovE. V.

Меркулов Евгений Владимирович.

Москва.

eLibrary SPIN 1181-7947

Evgeny V. Merkulov.

Moscow.

eLibrary SPIN 1181-7947

https://orcid.org/0000-0002-9822-4357ЧазоваИ. Е.ChazovaI. E.

Чазова Ирина Евгеньевна.

Москва.

eLibrary SPIN 6175-6138

Irina E. Chazova.

Moscow.

eLibrary SPIN 6175-6138

Национальный медицинский исследовательский центр кардиологии имени академика Е.И. ЧазоваРоссияNational Medical Research Centre of Cardiology named after academician E.I. ChazovRussian FederationНациональный медицинский исследовательский центр терапии и профилактической медициныРоссияFederal State Budgetary Institution National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of the Russian FederationRussian Federation202208092022184439448Copyright © Pevzner D.V., Kostritca N.S., Alieva A.K., Merkulova I.A., Yavelov I.S., Merkulov E.V., Chazova I.E., 20222022Певзнер Д.В., Кострица Н.С., Алиева А.К., Меркулова И.A., Явелов И.С., Меркулов Е.В., Чазова И.Е.Pevzner D.V., Kostritca N.S., Alieva A.K., Merkulova I.A., Yavelov I.S., Merkulov E.V., Chazova I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/2795Aim

Aim. To study the outcomes frequency and structure in patients with atrial fibrillation (AF) depending on the cardioembolic events preventing method: left atrial appendage (LAA) isolation, direct oral anticoagulants (DOACs) or warfarin.

Material and methods

Material and methods. A prospective observational study included patients with AF and high risk of cardioembolic complications and without contraindications to anticoagulants. Patients who refused long-term oral anticoagulants taking underwent LAA isolation, the rest of the patients received DOACs or warfarin. The observation period was 3 years. Mortality, cardioembolic complications and major bleeding (according to GARFIELD criteria) cumulative incidence was assessed.

Results

Results. We included 245 patients: 46 patients were treated with LAA isolation, 100 with warfarin, and 99 with DOACs. Multivariate regression analysis demonstrated a statistically significant advantage of LAA occluder in terms of combined endpoint achieving frequency compared to warfarin (hazard ratio [HR] 3.10; 95% confidence interval [CI] 1.01-9.54; p=0.049), and to DOACs (HR 3.44, 95% CI 1.15-10.29; p=0.027). A similar result was obtained for all-cause mortality (HR 5.24; 95% CI 1.12-24.55; p=0.036 and HR 5.58; 95% CI 1.22-25.49; p=0.027, respectively). There were no significant differences in bleeding rates between the groups.

Conclusion

Conclusion. This observational study demonstrates the superiority of LAA isolation as a first-line therapy over DOACs and warfarin in patients with AF and high risk of cardioembolic complications. Randomized trials are required to confirm these observations.

Цель

Цель. Изучить частоту и структуру прогноз-определяющих исходов у пациентов с фибрилляцией предсердий (ФП) в зависимости от метода профилактики кардиоэмболических событий: эндоваскулярной изоляции ушка левого предсердия (УЛП), применении прямых оральных антикоагулянтов (ПОАК) или варфарина.

Материал и методы

Материал и методы. В проспективное наблюдательное исследование включали пациентов с ФП и высоким риском кардиоэмболических осложнений, не имеющих противопоказаний к приему антикоагулянтов. Пациентам, которые отказались от длительного приема оральных антикоагулянтов, выполнялась эндоваскулярная изоляция УЛП, остальные пациенты получали ПОАК или варфарин. Период наблюдения составил 3 года. Оценивалась кумулятивная частота комбинированной конечной точки (смерти, кардиоэмболических осложнений и крупных кровотечений по критериям регистра GARFIELD.

Результаты

Результаты. Было включено 245 пациентов с ФП, из них в группу окклюдера УЛП - 46 пациентов, группу варфарина - 100, группу ПОАК -99. В многофакторном регрессионном анализе было продемонстрировано статистически значимое преимущество окклюдера УЛП в отношении частоты достижения комбинированной конечной точки как перед варфарином (относительный риск [ОР] 3,10, 95% доверительный интервал [ДИ] 1,01-9,54; p=0,049), так и перед ПОАК (ОР 3,44, 95% ДИ 1,15-10,29; p=0,027). Аналогичный результат был получен в отношении смерти от всех причин (ОР 5,24, 95% ДИ 1,12-24,55; p=0,036 и ОР 5,58, 95% ДИ 1,22-25,49; p=0,027, соответственно). Статистически значимых различий по частоте кровотечений между группами не было.

Заключение

Заключение. В данном наблюдательном исследовании продемонстрировано преимущество имплантации окклюдера УЛП перед ПОАК и варфарином по кумулятивной частоте прогноз-определяющих событий для пациентов с ФП и высоким риском кардиоэмболических осложнений в качестве первой линии терапии. Для подтверждения этих наблюдений требуются рандомизированные исследования.

фибрилляция предсердийокклюдер ушка левого предсердияпрямые оральные антикоагулянтыкардиоэмболические осложненияatrial fibrillationleft atrial appendage occluderdirect oral anticoagulantscardioembolic complicationsИсследование проведено при поддержке Национального медицинского исследовательского центра кардиологии имени академика Е.И. Чазова.The study was performed with the support of the National Medical Research Centre of Cardiology named after academician E.I. Chazov.ReferencesVirani, SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596. DOI:10.1161/cir.0000000000000757.Virani, SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596. DOI:10.1161/cir.0000000000000757.Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-88. DOI:10.1161/01.str.22.8.983.Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-88. DOI:10.1161/01.str.22.8.983.Gabet A, Guenancia C, Duloquin G, Olie V, Bejot Y Ischemic Stroke With Atrial Fibrillation: Characteristics and Time Trends 2006 to 2017 in the Dijon Stroke Registry. Stroke. 2021;52(6):2077-85. DOI:10.1161/STROKEAHA.120.030812.Gabet A, Guenancia C, Duloquin G, Olie V, Bejot Y Ischemic Stroke With Atrial Fibrillation: Characteristics and Time Trends 2006 to 2017 in the Dijon Stroke Registry. Stroke. 2021;52(6):2077-85. DOI:10.1161/STROKEAHA.120.030812.Odell JA, Blackshear JL, Davies E, et al. Thoracoscopic obliteration of the left atrial appendage: Potential for stroke reduction? Ann Thorac Surg. 1962;61(2):565-9. DOI:10.1016/0003-4975(95)00885-3.Odell JA, Blackshear JL, Davies E, et al. Thoracoscopic obliteration of the left atrial appendage: Potential for stroke reduction? Ann Thorac Surg. 1962;61(2):565-9. DOI:10.1016/0003-4975(95)00885-3.Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42(5):373-498. DOI:10.1093/eurheartj/ehaa612.Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42(5):373-498. DOI:10.1093/eurheartj/ehaa612.January ST, Wann LS, 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. J Am Coll Cardiol. 2019;74(1):104-32. DOI:10.1016/j.jacc.2019.01.011.January ST, Wann LS, 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. J Am Coll Cardiol. 2019;74(1):104-32. DOI:10.1016/j.jacc.2019.01.011.Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiortiy trial. Lancet. 2009;374(9689):534-42. DOI:10.1016/S0140-6736(09)61343-X.Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiortiy trial. Lancet. 2009;374(9689):534-42. DOI:10.1016/S0140-6736(09)61343-X.Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1-12. DOI:10.1016/j.jacc.2014.04.029.Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1-12. DOI:10.1016/j.jacc.2014.04.029.Osmancik P, Herman D, Neuzil P, et al. PRAGUE-17 Trial Investigators. Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation. J Am Coll Cardiol. 2020;75(25):3122-35. DOI:10.1016/j.jacc.2020.04.067.Osmancik P, Herman D, Neuzil P, et al. PRAGUE-17 Trial Investigators. Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation. J Am Coll Cardiol. 2020;75(25):3122-35. DOI:10.1016/j.jacc.2020.04.067.Glikson M, Wolff R, Hindricks G, et al. ESC Scientific Document Group. EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion - an update. Europace. 2020;22(2):184. DOI:10.1093/europace/euz258.Glikson M, Wolff R, Hindricks G, et al. ESC Scientific Document Group. EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion - an update. Europace. 2020;22(2):184. DOI:10.1093/europace/euz258.Franco L, Becattini C, Beyer-Westendorf J, et al. Definition of major bleeding: Prognostic classification. J Thromb Haemost. 2020;18(11):2852-60. DOI:10.1111/jth.15048.Franco L, Becattini C, Beyer-Westendorf J, et al. Definition of major bleeding: Prognostic classification. J Thromb Haemost. 2020;18(11):2852-60. DOI:10.1111/jth.15048.Reddy VY, Sievert H, Halperin J, et al. PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. J Am Med Assoc. 2014;312(19):1988-98. DOI:10.1001/jama.2014.15192.Reddy VY, Sievert H, Halperin J, et al. PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. J Am Med Assoc. 2014;312(19):1988-98. DOI:10.1001/jama.2014.15192.Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. DOI:10.1056/NEJMoa0905561.Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. DOI:10.1056/NEJMoa0905561.Patel MR, Mahaffey KW, Garg J, et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. DOI:10.1056/NEJMoa1009638.Patel MR, Mahaffey KW, Garg J, et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. DOI:10.1056/NEJMoa1009638.Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. DOI:10.1056/NEJMoa1107039.Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92. DOI:10.1056/NEJMoa1107039.Giugliano RP, Ruff CT, Braunwald E, et al. ENGAGE AF-TIMI Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-104. DOI:10.1056/NEJMoa1310907.Giugliano RP, Ruff CT, Braunwald E, et al. ENGAGE AF-TIMI Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-104. DOI:10.1056/NEJMoa1310907.Connolly S, Pogue J, Hart R, et al. ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903-12. DOI:10.1016/S0140-6736(06)68845-4.Connolly S, Pogue J, Hart R, et al. ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903-12. DOI:10.1016/S0140-6736(06)68845-4.Mant J, Hobbs FD, Fletcher K, et al. BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493-503. DOI:10.1016/S0140-6736(07)61233-1.Mant J, Hobbs FD, Fletcher K, et al. BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493-503. DOI:10.1016/S0140-6736(07)61233-1.Reddy VY, Doshi SK, Kar S, et al. PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J Am Coll Cardiol. 2017;70(24):2964-75. DOI:10.1016/j.jacc.2017.10.021.Reddy VY, Doshi SK, Kar S, et al. PREVAIL and PROTECT AF Investigators. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J Am Coll Cardiol. 2017;70(24):2964-75. DOI:10.1016/j.jacc.2017.10.021.Давтян К.В., Калемберг А.А., Симонян Г.Ю. Эффективность профилактики ишемического инсульта у пациентов с имплантированным окклюзирующим устройством ушка левого предсердия. Результаты пятилетнего наблюдения. Российский Кардиологический Журнал. 2018;(7):16-20. DOI:10.15829/1560-4071-2018-7-16-20.Davtyan KV, Kalemberg AA, Simonian GYu, et al. Efficacy of ischemic stroke prevention in patients with implanted occluder of the left atrium. five year follow-up. Russian Journal of Cardiology. 2018;(7):16-20 (In Russ.) DOI:10.15829/1560-4071-2018-7-16-20.Turagam MK, Osmancik P, Neuzil P, et al. Left atrial appendage closure versus oral anticoagulants in atrial fibrillation: a meta-analysis of randomized trials. J Am Coll Cardiol. 2020;76(23):2795-7. DOI:10.1016/j.jacc.2020.08.089.Turagam MK, Osmancik P, Neuzil P, et al. Left atrial appendage closure versus oral anticoagulants in atrial fibrillation: a meta-analysis of randomized trials. J Am Coll Cardiol. 2020;76(23):2795-7. DOI:10.1016/j.jacc.2020.08.089.Boersma LV, Schmidt B, Betts TR, et al. EWOLUTION investigators. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. Eur Heart J. 2016;37(31):2465-74. DOI:10.1093/eurheartj/ehv730.Boersma LV, Schmidt B, Betts TR, et al. EWOLUTION investigators. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. Eur Heart J. 2016;37(31):2465-74. DOI:10.1093/eurheartj/ehv730.Шугушев Э.Х., Родионова Л.В., Ганеева О.Н., и др. Непосредственные и отдаленные результаты имплантации окклюдера ушка левого предсердия у больных с фибрилляцией предсердия. Российский Кардиологический Журнал. 2020;(12):28-32. DOI:10.15829/1560-4071-2016-12-28-32.Shugushev ZK, Rodionova LV, Ganeeva ON, et al. Immediate and long-term results of the left atrium auricle occluder implanting in atrial fibrillation. Russian Journal of Cardiology. 2016;(12):28-32 (In Russ.) DOI:10.15829/1560-4071-2016-12-28-32.Tzikas A, Shakir S, Gafoor S et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention. 2016;11(10):1170-9. DOI:10.4244/EIJY15M01_06.Tzikas A, Shakir S, Gafoor S et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention. 2016;11(10):1170-9. DOI:10.4244/EIJY15M01_06.

The authors declare that there are no conflicts of interest present.