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Характеристика и исходы за 5 лет наблюдения у пациентов с хроническим лимфоцитарным лейкозом, получающих ибрутиниб (исследование реальной клинической практики)
Характеристика и исходы за 5 лет наблюдения у пациентов с хроническим лимфоцитарным лейкозом, получающих ибрутиниб (исследование реальной клинической практики)
Эргашева У.П., Панченко Е.П., Чернышенко Е.Г., Дмитриева Е.А., Кислова М.И., Федоткина Ю.А., Яровая Е.Б., Римашевская Е.В., Птушкин В.В., Никитин Е.А. Характеристика и исходы за 5 лет наблюдения у пациентов с хроническим лимфоцитарным лейкозом, получающих ибрутиниб (исследование реальной клинической практики). Терапевтический архив. 2026;98(1):56–65. DOI: 10.26442/00403660.2026.01.203492
© ООО «КОНСИЛИУМ МЕДИКУМ», 2026 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2026 г.
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Аннотация
Цель. Оценить основные сердечно-сосудистые осложнения у пациентов с хроническим лимфоцитарным лейкозом (ХЛЛ), получающих ибрутиниб, и охарактеризовать больных с впервые возникшей фибрилляцией предсердий (ФП) на терапии ибрутинибом и их исходы в условиях реальной клинической практики.
Материалы и методы. Проведен ретроспективный анализ медицинской документации 641 пациента с ХЛЛ на терапии ибрутинибом, наблюдавшегося на базе гематологического центра ГБУЗ «ММНКЦ им. С.П. Боткина» в период с 2013 по 2024 г. Первичная конечная точка исследования – возникновение ФП на терапии ибрутинибом. Вторичной конечной точкой исследования являлись тромботические и геморрагические осложнения. Для оценки влияния ФП на исходы больных проводилось сопоставление пациентов с ФП и без ФП по полу и возрасту. Для оценки исходов использовалась комбинированная конечная точка, включающая сердечно-сосудистую смерть и фатальные кровотечения.
Результаты. Частота впервые возникшей ФП на терапии ибрутинибом за 5-летний период наблюдения составила 15%. Пациенты с возникшей ФП во время приема ибрутиниба оказались старше пациентов без ФП и характеризовались наличием стандартных факторов риска ФП, при этом различий в характеристиках ХЛЛ и противоопухолевой терапии не выявлено. Возникновение ФП на терапии ибрутинибом ассоциируется с четырехкратным увеличением риска развития тромботических осложнений (отношение рисков 4,071, 95% доверительный интервал 1,837–9,024; р<0,001), в том числе с увеличением частоты фатальной тромбоэмболии легочной артерии (р=0,035) при сопоставимой частоте фатальных кровотечений.
Заключение. Частота возникновения ФП у больных ХЛЛ на терапии ибрутинибом значимо превышает частоту ФП у пожилых пациентов без ХЛЛ. Возникновение ФП во время терапии ибрутинибом ассоциируется с увеличением частоты тромботических осложнений, в том числе фатальных, при сопоставимой частоте фатальных геморрагических осложнений.
Ключевые слова: хронический лимфоцитарный лейкоз, ибрутиниб, сердечно-сосудистые нежелательные явления, фибрилляция предсердий, кровоточивость, тромботические осложнения
Materials and methods. A retrospective analysis of the medical records of 641 patients diagnosed with CLL who were treated with ibrutinib at the haematology centre of the Botkin Moscow Multidisciplinary Scientific and Clinical Center from 2013 to 2024 was conducted. The primary endpoint of the study was the occurrence of atrial fibrillation during ibrutinib therapy. The secondary endpoint of the study was thrombotic and haemorrhagic complications. To assess the impact of AF on patient outcomes, a comparison was made between patients with AF and those without AF based on sex and age. A composite endpoint was used to evaluate outcomes, which included cardiovascular death and fatal bleeding.
Results. The incidence of new-onset AF in patients receiving ibrutinib therapy during the five-year was 15%. Patients with AF occurring during ibrutinib therapy were found to be older and characterised by the presence of standard risk factors for AF. No significant differences were observed in the characteristics of CLL and its treatment. The occurrence of AF during ibrutinib therapy was associated with a fourfold increased risk of thrombotic complications (OR 4.071, 95% CI 1.837–9.024; p<0.001), including an increased incidence of fatal pulmonary embolism (p=0.035) with a comparable incidence of fatal bleeding.
Conclusion. The incidence of AF in patients with CLL receiving ibrutinib is significantly higher than the incidence of AF in elderly patients without CLL. The occurrence of new-onset AF during ibrutinib therapy has been observed to be associated with an increased incidence of thrombotic complications, including fatal thrombotic complications. The incidence of fatal haemorrhagic complications has been noted to be comparable.
Keywords: chronic lymphocytic leukaemia, ibrutinib, cardiovascular adverse events, atrial fibrillation, bleeding, thrombotic complications
Материалы и методы. Проведен ретроспективный анализ медицинской документации 641 пациента с ХЛЛ на терапии ибрутинибом, наблюдавшегося на базе гематологического центра ГБУЗ «ММНКЦ им. С.П. Боткина» в период с 2013 по 2024 г. Первичная конечная точка исследования – возникновение ФП на терапии ибрутинибом. Вторичной конечной точкой исследования являлись тромботические и геморрагические осложнения. Для оценки влияния ФП на исходы больных проводилось сопоставление пациентов с ФП и без ФП по полу и возрасту. Для оценки исходов использовалась комбинированная конечная точка, включающая сердечно-сосудистую смерть и фатальные кровотечения.
Результаты. Частота впервые возникшей ФП на терапии ибрутинибом за 5-летний период наблюдения составила 15%. Пациенты с возникшей ФП во время приема ибрутиниба оказались старше пациентов без ФП и характеризовались наличием стандартных факторов риска ФП, при этом различий в характеристиках ХЛЛ и противоопухолевой терапии не выявлено. Возникновение ФП на терапии ибрутинибом ассоциируется с четырехкратным увеличением риска развития тромботических осложнений (отношение рисков 4,071, 95% доверительный интервал 1,837–9,024; р<0,001), в том числе с увеличением частоты фатальной тромбоэмболии легочной артерии (р=0,035) при сопоставимой частоте фатальных кровотечений.
Заключение. Частота возникновения ФП у больных ХЛЛ на терапии ибрутинибом значимо превышает частоту ФП у пожилых пациентов без ХЛЛ. Возникновение ФП во время терапии ибрутинибом ассоциируется с увеличением частоты тромботических осложнений, в том числе фатальных, при сопоставимой частоте фатальных геморрагических осложнений.
Ключевые слова: хронический лимфоцитарный лейкоз, ибрутиниб, сердечно-сосудистые нежелательные явления, фибрилляция предсердий, кровоточивость, тромботические осложнения
________________________________________________
Materials and methods. A retrospective analysis of the medical records of 641 patients diagnosed with CLL who were treated with ibrutinib at the haematology centre of the Botkin Moscow Multidisciplinary Scientific and Clinical Center from 2013 to 2024 was conducted. The primary endpoint of the study was the occurrence of atrial fibrillation during ibrutinib therapy. The secondary endpoint of the study was thrombotic and haemorrhagic complications. To assess the impact of AF on patient outcomes, a comparison was made between patients with AF and those without AF based on sex and age. A composite endpoint was used to evaluate outcomes, which included cardiovascular death and fatal bleeding.
Results. The incidence of new-onset AF in patients receiving ibrutinib therapy during the five-year was 15%. Patients with AF occurring during ibrutinib therapy were found to be older and characterised by the presence of standard risk factors for AF. No significant differences were observed in the characteristics of CLL and its treatment. The occurrence of AF during ibrutinib therapy was associated with a fourfold increased risk of thrombotic complications (OR 4.071, 95% CI 1.837–9.024; p<0.001), including an increased incidence of fatal pulmonary embolism (p=0.035) with a comparable incidence of fatal bleeding.
Conclusion. The incidence of AF in patients with CLL receiving ibrutinib is significantly higher than the incidence of AF in elderly patients without CLL. The occurrence of new-onset AF during ibrutinib therapy has been observed to be associated with an increased incidence of thrombotic complications, including fatal thrombotic complications. The incidence of fatal haemorrhagic complications has been noted to be comparable.
Keywords: chronic lymphocytic leukaemia, ibrutinib, cardiovascular adverse events, atrial fibrillation, bleeding, thrombotic complications
Полный текст
Список литературы
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20. Wiczer TE, Levine LB, Brumbaugh J, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739-48. DOI:10.1182/bloodadvances.2017009720
21. Ojo A, Goldenberg I, McNitt S, et al. Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma. JACC Adv. 2023;2(8):100602. DOI:10.1016/j.jacadv.2023.100602
22. Onitilo AA, Piwuna TO, Islam N, et al. Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy. Clin Med Res. 2022;20(1):16-22. DOI:10.3121/cmr.2021.1693
23. Eichhorst B, Hallek M, Goede V. Management of unfit elderly patients with chronic lymphocytic leukemia. Eur J Intern Med. 2018;58:7-13. DOI:10.1016/j.ejim.2018.02.001
24. Rasmussen KM, Patil V, Burningham Z, et al. Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration. Fed Pract. 2020;37(Suppl. 2):S44-9.
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26. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809-15. DOI:10.1001/archinte.160.6.809
27. Avalon JC, Fuqua J, Miller T, et al. Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib. Cardiooncology. 2021;7(1):38. DOI:10.1186/s40959-021-00125-8
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2. Khronicheskii limfoleikoz. Sovremennaia diagnostika i lechenie. Pod red. EA Nikitina, VV Ptushkina. 2-e izd., pererab. i dop. Moscow: GEOTAR-Media, 2023 (in Russian). DOI:10.33029/9704-7597-3-SDL-2023-1-480
3. Nikitin EA, Panteleev MA, Emelina EI, et al. Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia. Clinical Oncohematology. 2017;10(3):271-81 (in Russian). DOI:10.21320/2500-2139-2017-10-3-271-281
4. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-23. DOI:10.1056/NEJMoa1400376
5. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-37. DOI:10.1056/NEJMoa1509388
6. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. DOI:10.1016/S1470-2045(18)30788-5
7. Caldeira D, Alves D, Costa J, et al. Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis. PLoS One. 2019;14(2):e0211228. DOI:10.1371/journal.pone.0211228
8. Córdoba R, Bayés-Genís A, Muntañola A, et al. In silico analysis of atrial fibrillation and hypertension mechanism of action secondary to ibrutinib/acalabrutinib in chronic lymphocytic leukemia. Sci Rep. 2025;15(1):28040. DOI:10.1038/s41598-025-07756-2
9. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60. DOI:10.1182/blood-2017-09-806398
10. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206. DOI:10.1002/1097-0142(19810701)48:1<198::aid-cncr2820480131>3.0.co;2-v
11. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414. DOI:10.1093/eurheartj/ehae176
12. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res. 1992;41(3):237-48. DOI:10.1016/0165-1781(92)90005-n
13. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736-47. DOI:10.1161/CIRCULATIONAHA.110.009449
14. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 20019;285(18):2370-5. DOI:10.1001/jama.285.18.2370
15. Hobbs FD, Fitzmaurice DA, Mant J, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess. 2005;9(40):iii-iv, ix-x, 1-74. DOI:10.3310/hta9400
16. Ganatra S, Sharma A, Shah S, et al. Ibrutinib-Associated Atrial Fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491-500. DOI:10.1016/j.jacep.2018.06.004
17. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-361. DOI:10.1093/eurheartj/ehac244
18. Stilgenbauer S, Jones JA, Coutre SE, et al. Results from the phase 2 RESONATE™-17 trial: efficacy and safety of Ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with Del17p. Oncol Res Treat. 2015;38(Suppl. 5):92. abstract V291.
19. UK CLL Forum. Ibrutinib for relapsed/refractory chronic lymphocytic leukemia: a UK and Ireland analysis of outcomes in 315 patients. Haematologica. 2016;101(12):1563-72. DOI:10.3324/haematol.2016.147900
20. Wiczer TE, Levine LB, Brumbaugh J, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739-48. DOI:10.1182/bloodadvances.2017009720
21. Ojo A, Goldenberg I, McNitt S, et al. Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma. JACC Adv. 2023;2(8):100602. DOI:10.1016/j.jacadv.2023.100602
22. Onitilo AA, Piwuna TO, Islam N, et al. Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy. Clin Med Res. 2022;20(1):16-22. DOI:10.3121/cmr.2021.1693
23. Eichhorst B, Hallek M, Goede V. Management of unfit elderly patients with chronic lymphocytic leukemia. Eur J Intern Med. 2018;58:7-13. DOI:10.1016/j.ejim.2018.02.001
24. Rasmussen KM, Patil V, Burningham Z, et al. Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration. Fed Pract. 2020;37(Suppl. 2):S44-9.
25. Gambril JA, Ghazi SM, Sansoterra S, et al. Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation. Leukemia. 2024;38(10):2141-9. DOI:10.1038/s41375-024-02334-3
26. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809-15. DOI:10.1001/archinte.160.6.809
27. Avalon JC, Fuqua J, Miller T, et al. Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib. Cardiooncology. 2021;7(1):38. DOI:10.1186/s40959-021-00125-8
28. Krivosheeva EN, Kropacheva ES, Dobrovolskii AB, et al. Growth differentiation factor 15 and the risk of cardiovascular events in patients with atrial fibrillation after elective percutaneous coronary intervention. Russian Journal of Cardiology.2021;26(7):4457 (in Russian). DOI:10.15829/1560-4071-2021-4457
29. Podzolkov VI, Tarzimanova AI, Bragina AE, et al. The importance of matrix metalloproteinases in the development of atrial fibrillation in obesity. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(12):1451-6 (in Russian). DOI:10.26442/00403660.2021.12.201178
2. Хронический лимфолейкоз. Современная диагностика и лечение. Под ред. Е.А. Никитина, В.В. Птушкина. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2023 [Khronicheskii limfoleikoz. Sovremennaia diagnostika i lechenie. Pod red. EA Nikitina, VV Ptushkina. 2-e izd., pererab. i dop. Moscow: GEOTAR-Media, 2023 (in Russian)]. DOI:10.33029/9704-7597-3-SDL-2023-1-480
3. Никитин Е.А., Пантелеев М.А., Емелина Е.И., и др. Ибрутиниб в лечении рефрактерного хронического лимфолейкоза. Клиническая онкогематология. 2017;10(3):271-81 [Nikitin EA, Panteleev MA, Emelina EI, et al. Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia. Clinical Oncohematology. 2017;10(3):271-81 (in Russian)]. DOI:10.21320/2500-2139-2017-10-3-271-281
4. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-23. DOI:10.1056/NEJMoa1400376
5. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-37. DOI:10.1056/NEJMoa1509388
6. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. DOI:10.1016/S1470-2045(18)30788-5
7. Caldeira D, Alves D, Costa J, et al. Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis. PLoS One. 2019;14(2):e0211228. DOI:10.1371/journal.pone.0211228
8. Córdoba R, Bayés-Genís A, Muntañola A, et al. In silico analysis of atrial fibrillation and hypertension mechanism of action secondary to ibrutinib/acalabrutinib in chronic lymphocytic leukemia. Sci Rep. 2025;15(1):28040. DOI:10.1038/s41598-025-07756-2
9. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60. DOI:10.1182/blood-2017-09-806398
10. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206. DOI:10.1002/1097-0142(19810701)48:1<198::aid-cncr2820480131>3.0.co;2-v
11. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414. DOI:10.1093/eurheartj/ehae176
12. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res. 1992;41(3):237-48. DOI:10.1016/0165-1781(92)90005-n
13. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736-47. DOI:10.1161/CIRCULATIONAHA.110.009449
14. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 20019;285(18):2370-5. DOI:10.1001/jama.285.18.2370
15. Hobbs FD, Fitzmaurice DA, Mant J, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess. 2005;9(40):iii-iv, ix-x, 1-74. DOI:10.3310/hta9400
16. Ganatra S, Sharma A, Shah S, et al. Ibrutinib-Associated Atrial Fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491-500. DOI:10.1016/j.jacep.2018.06.004
17. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-361. DOI:10.1093/eurheartj/ehac244
18. Stilgenbauer S, Jones JA, Coutre SE, et al. Results from the phase 2 RESONATE™-17 trial: efficacy and safety of Ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with Del17p. Oncol Res Treat. 2015;38(Suppl. 5):92. abstract V291.
19. UK CLL Forum. Ibrutinib for relapsed/refractory chronic lymphocytic leukemia: a UK and Ireland analysis of outcomes in 315 patients. Haematologica. 2016;101(12):1563-72. DOI:10.3324/haematol.2016.147900
20. Wiczer TE, Levine LB, Brumbaugh J, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739-48. DOI:10.1182/bloodadvances.2017009720
21. Ojo A, Goldenberg I, McNitt S, et al. Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma. JACC Adv. 2023;2(8):100602. DOI:10.1016/j.jacadv.2023.100602
22. Onitilo AA, Piwuna TO, Islam N, et al. Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy. Clin Med Res. 2022;20(1):16-22. DOI:10.3121/cmr.2021.1693
23. Eichhorst B, Hallek M, Goede V. Management of unfit elderly patients with chronic lymphocytic leukemia. Eur J Intern Med. 2018;58:7-13. DOI:10.1016/j.ejim.2018.02.001
24. Rasmussen KM, Patil V, Burningham Z, et al. Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration. Fed Pract. 2020;37(Suppl. 2):S44-9.
25. Gambril JA, Ghazi SM, Sansoterra S, et al. Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation. Leukemia. 2024;38(10):2141-9. DOI:10.1038/s41375-024-02334-3
26. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809-15. DOI:10.1001/archinte.160.6.809
27. Avalon JC, Fuqua J, Miller T, et al. Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib. Cardiooncology. 2021;7(1):38. DOI:10.1186/s40959-021-00125-8
28. Кривошеева Е.Н., Кропачева Е.С., Добровольский А.Б., и др. Ростовой фактор дифференцировки-15 и риск сердечно-сосудистых осложнений у пациентов с фибрилляцией предсердий после планового чрескожного коронарного вмешательства. Российский кардиологический журнал. 2021;26(7):4457 [Krivosheeva EN, Kropacheva ES, Dobrovolskii AB, et al. Growth differentiation factor 15 and the risk of cardiovascular events in patients with atrial fibrillation after elective percutaneous coronary intervention. Russian Journal of Cardiology.2021;26(7):4457 (in Russian)]. DOI:10.15829/1560-4071-2021-4457
29. Подзолков В.И., Тарзиманова А.И., Брагина А.Е., и др. Значение матриксных металлопротеиназ в развитии фибрилляции предсердий при ожирении. Терапевтический архив. 2021;93(12):1451-6 [Podzolkov VI, Tarzimanova AI, Bragina AE, et al. The importance of matrix metalloproteinases in the development of atrial fibrillation in obesity. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(12):1451-6 (in Russian)]. DOI:10.26442/00403660.2021.12.201178
________________________________________________
2. Khronicheskii limfoleikoz. Sovremennaia diagnostika i lechenie. Pod red. EA Nikitina, VV Ptushkina. 2-e izd., pererab. i dop. Moscow: GEOTAR-Media, 2023 (in Russian). DOI:10.33029/9704-7597-3-SDL-2023-1-480
3. Nikitin EA, Panteleev MA, Emelina EI, et al. Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia. Clinical Oncohematology. 2017;10(3):271-81 (in Russian). DOI:10.21320/2500-2139-2017-10-3-271-281
4. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-23. DOI:10.1056/NEJMoa1400376
5. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-37. DOI:10.1056/NEJMoa1509388
6. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. DOI:10.1016/S1470-2045(18)30788-5
7. Caldeira D, Alves D, Costa J, et al. Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis. PLoS One. 2019;14(2):e0211228. DOI:10.1371/journal.pone.0211228
8. Córdoba R, Bayés-Genís A, Muntañola A, et al. In silico analysis of atrial fibrillation and hypertension mechanism of action secondary to ibrutinib/acalabrutinib in chronic lymphocytic leukemia. Sci Rep. 2025;15(1):28040. DOI:10.1038/s41598-025-07756-2
9. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60. DOI:10.1182/blood-2017-09-806398
10. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206. DOI:10.1002/1097-0142(19810701)48:1<198::aid-cncr2820480131>3.0.co;2-v
11. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414. DOI:10.1093/eurheartj/ehae176
12. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res. 1992;41(3):237-48. DOI:10.1016/0165-1781(92)90005-n
13. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736-47. DOI:10.1161/CIRCULATIONAHA.110.009449
14. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 20019;285(18):2370-5. DOI:10.1001/jama.285.18.2370
15. Hobbs FD, Fitzmaurice DA, Mant J, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess. 2005;9(40):iii-iv, ix-x, 1-74. DOI:10.3310/hta9400
16. Ganatra S, Sharma A, Shah S, et al. Ibrutinib-Associated Atrial Fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491-500. DOI:10.1016/j.jacep.2018.06.004
17. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-361. DOI:10.1093/eurheartj/ehac244
18. Stilgenbauer S, Jones JA, Coutre SE, et al. Results from the phase 2 RESONATE™-17 trial: efficacy and safety of Ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with Del17p. Oncol Res Treat. 2015;38(Suppl. 5):92. abstract V291.
19. UK CLL Forum. Ibrutinib for relapsed/refractory chronic lymphocytic leukemia: a UK and Ireland analysis of outcomes in 315 patients. Haematologica. 2016;101(12):1563-72. DOI:10.3324/haematol.2016.147900
20. Wiczer TE, Levine LB, Brumbaugh J, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739-48. DOI:10.1182/bloodadvances.2017009720
21. Ojo A, Goldenberg I, McNitt S, et al. Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma. JACC Adv. 2023;2(8):100602. DOI:10.1016/j.jacadv.2023.100602
22. Onitilo AA, Piwuna TO, Islam N, et al. Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy. Clin Med Res. 2022;20(1):16-22. DOI:10.3121/cmr.2021.1693
23. Eichhorst B, Hallek M, Goede V. Management of unfit elderly patients with chronic lymphocytic leukemia. Eur J Intern Med. 2018;58:7-13. DOI:10.1016/j.ejim.2018.02.001
24. Rasmussen KM, Patil V, Burningham Z, et al. Atrial Fibrillation and Bleeding in Patients With Chronic Lymphocytic Leukemia Treated with Ibrutinib in the Veterans Health Administration. Fed Pract. 2020;37(Suppl. 2):S44-9.
25. Gambril JA, Ghazi SM, Sansoterra S, et al. Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation. Leukemia. 2024;38(10):2141-9. DOI:10.1038/s41375-024-02334-3
26. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809-15. DOI:10.1001/archinte.160.6.809
27. Avalon JC, Fuqua J, Miller T, et al. Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib. Cardiooncology. 2021;7(1):38. DOI:10.1186/s40959-021-00125-8
28. Krivosheeva EN, Kropacheva ES, Dobrovolskii AB, et al. Growth differentiation factor 15 and the risk of cardiovascular events in patients with atrial fibrillation after elective percutaneous coronary intervention. Russian Journal of Cardiology.2021;26(7):4457 (in Russian). DOI:10.15829/1560-4071-2021-4457
29. Podzolkov VI, Tarzimanova AI, Bragina AE, et al. The importance of matrix metalloproteinases in the development of atrial fibrillation in obesity. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(12):1451-6 (in Russian). DOI:10.26442/00403660.2021.12.201178
Авторы
У.П. Эргашева*1, Е.П. Панченко1, Е.Г. Чернышенко2,3, Е.А. Дмитриева4,5, М.И. Кислова4, Ю.А. Федоткина1, Е.Б. Яровая2,3, Е.В. Римашевская5, В.В. Птушкин4, Е.А. Никитин4,5
1ФГБУ «Национальный медицинский исследовательский центр кардиологии им. акад. Е.И. Чазова» Минздрава России, Москва, Россия;
2ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3ФГБОУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава России, Москва, Россия;
4ГБУЗ «Московский многопрофильный научно-клинический центр им С.П. Боткина» Департамента здравоохранения г. Москвы, Москва, Россия;
5ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия
*Ergasheva1998@inbox.ru
1Chazov National Medical Research Center of Cardiology, Moscow, Russia;
2Lomonosov Moscow State University, Moscow, Russia;
3National Research Center for Therapy and Preventive Medicine, Moscow, Russia;
4Botkin Moscow Multidisciplinary Scientific and Clinical Center, Moscow, Russia;
5Russian Medical Academy of Continuous Professional Education, Moscow, Russia
*Ergasheva1998@inbox.ru
1ФГБУ «Национальный медицинский исследовательский центр кардиологии им. акад. Е.И. Чазова» Минздрава России, Москва, Россия;
2ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3ФГБОУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава России, Москва, Россия;
4ГБУЗ «Московский многопрофильный научно-клинический центр им С.П. Боткина» Департамента здравоохранения г. Москвы, Москва, Россия;
5ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия
*Ergasheva1998@inbox.ru
________________________________________________
1Chazov National Medical Research Center of Cardiology, Moscow, Russia;
2Lomonosov Moscow State University, Moscow, Russia;
3National Research Center for Therapy and Preventive Medicine, Moscow, Russia;
4Botkin Moscow Multidisciplinary Scientific and Clinical Center, Moscow, Russia;
5Russian Medical Academy of Continuous Professional Education, Moscow, Russia
*Ergasheva1998@inbox.ru
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