medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-312medsovet-8492Research ArticleКАРДИОЛОГИЯCARDIOLOGYУровень фактора Х свертывания и риски развития нежелательных реакций при терапии ривароксабаном и апиксабаном у пациентов с неклапанной фибрилляцией предсердийThe level of factor X coagulation and the risk of adverse reactions during treatment with rivaroxaban and apixaban in patients with non-valvular atrial fibrillationhttps://orcid.org/0000-0002-0424-2352КочетковаЕ. К.KochetkovaE. K.

Кочеткова Елена Константиновна - аспирант кафедры клинической фармакологии и пропедевтики внутренних болезней.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Elena K. Kochetkova - Graduate Student of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

kochetkovahelen@yandex.ruhttps://orcid.org/0000-0002-7430-3341АстаповскийА. А.AstapovskiiA. A.

Астаповский Александр Алексеевич - к.м.н., доцент кафедры клинической фармакологии и пропедевтики внутренних болезней.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Alexandr A. Astapovskii - Cand. Sci. (Med.), Associate Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

al.astapovskii@gmail.comhttps://orcid.org/0009-0007-2410-2457КулагинаН. П.KulaginaN. P.

Кулагина Наталья Петровна - заведующая 1-м кардиологическим отделением.

129336, Москва, ул. Стартовая, д. 4

Natalya P. Kulagina - Head of the 1st Cardiology Department, Hospital for War Veterans No. 3.

4, Startovaya St., Moscow, 129336

sccorpio66@mail.ruhttps://orcid.org/0000-0002-0535-2916ДроздовВ. Н.DrozdovV. N.

Дроздов Владимир Николаевич - д.м.н., профессор, профессор кафедры клинической фармакологии и пропедевтики внутренних болезней.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Vladimir N. Drozdov - Dr. Sci. (Med.), Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

vndrozdov@yandex.ruhttps://orcid.org/0000-0001-7234-4185МелконянГ. Г.MelkonyanG. G.

Мелконян Георгий Геннадьевич - д.м.н., профессор кафедры хирургии дополнительного профессионального образования РМАНПО; главный врач ГВВ № 3.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1; 129336, Москва, ул. Стартовая, д. 4

George G. Melkonyan - Dr. Sci. (Med.), Chief Doctor, Hospital for War Veterans No. 3; Professor of the Surgery Department, Russian Medical Academy of Continuous Professional Education.

4, Startovaya St., Moscow, 129336; 2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

melkonyan_g_g@staff.sechenov.ruhttps://orcid.org/0000-0002-7163-7119СереброваС. Ю.SerebrovaS. Yu.

Сереброва Светлана Юрьевна - д.м.н., главный научный сотрудник, НЦЭСМП; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней, ПМГМУ им. И.М. Сеченова (Сеченовский Университет).

127051, Москва, Петровский бульвар, д. 8, стр. 2; 119991, Москва, ул. Трубецкая, д. 8, стр. 2

Svetlana Yu. Serebrova - Dr. Sci. (Med.), Chief Scientific Officer, Scientific Centre for Expert Evaluation of Medicinal Products; Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051; 8, Bldg. 2, Trubetskaya St., Moscow, 119991

svetaserebrova@mail.ruhttps://orcid.org/0000-0001-6589-7654ШихЕ. В.ShikhE. V.

Ших Евгения Валерьевна - д.м.н., профессор, заведующая кафедрой клинической фармакологии и пропедевтики внутренних болезней.

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Evgenia V. Shikh - Dr. Sci. (Med.), Chair of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Trubetskaya St., Moscow, 119991

chih@mail.ruПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian FederationГоспиталь для ветеранов войн №3РоссияHospital for War Veterans No. 3Russian FederationГоспиталь для ветеранов войн №3; Российская медицинская академия непрерывного профессионального образованияРоссияHospital for War Veterans No. 3; Russian Medical Academy of Continuous Professional EducationRussian FederationПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет); Научный центр экспертизы средств медицинского примененияРоссияSechenov First Moscow State Medical University (Sechenov University); Scientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2024010920240131622Copyright © Кочеткова Е.К., Астаповский А.А., Кулагина Н.П., Дроздов В.Н., Мелконян Г.Г., Сереброва С.Ю., Ших Е.В., 20242024Кочеткова Е.К., Астаповский А.А., Кулагина Н.П., Дроздов В.Н., Мелконян Г.Г., Сереброва С.Ю., Ших Е.В.Kochetkova E.K., Astapovskii A.A., Kulagina N.P., Drozdov V.N., Melkonyan G.G., Serebrova S.Y., Shikh E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8492Введение

Введение. Ингибиторы Ха-фактора имеют важное значение для пациентов с фибрилляцией предсердий, снижая риск инсульта. Однако уровень непосредственно Х фактора в крови у таких пациентов изучен недостаточно.

Цель

Цель. Оценить влияние уровня Х фактора свертывания крови на риск развития нежелательных лекарственных реакций (НЛР) у пациентов, принимающих апиксабан и ривароксабан.

Материалы и методы

Материалы и методы. Исследование включало 102 пациента с фибрилляцией предсердий, принимавших ингибиторы Ха (иХа): 56 - ривароксабан, 46 - апиксабан. Регистрировались нежелательные лекарственные реакции в медицинской документации за время приема препарата. Концентрация Х фактора определялась методом фотоколориметрии при помощи реактивов для определения концентрации Х фактора - AssaySense Human Factor X (FX) Chromogenic Activity Assay Kit (AssayPro, США).

Результаты

Результаты. У пациентов, получавших апиксабан, в 32,6% случаев концентрация Х фактора была ниже, а у 43,5% пациентов - выше референтных значений. У пациентов, получавших ривароксабан, эти показатели составляли 26,8 и 51,8% соответственно. Всего, по данным медицинской документации, зарегистрировано 37 (36,2%) нежелательных реакций у 29 (28,4%) пациентов, в т. ч. 23 (41,1%) НЛР у 19 (33,9%) пациентов, принимавших ривароксабан, и 14 (30,4%) НЛР у 10 (21,7%) пациентов, принимавших апиксабан. Уровень Х фактора статистически значимо был связан с риском инсульта (AUC ROC = 0,720, р = 0,05) и малого кровотечения (AUC ROC = 0,735, р = 0,003): повышение уровня более 12,6 мкк/мл увеличивало риск инсульта (1,9-74,3; ДИ 95%, р = 0,034) в 9,4 раза, а уменьшение до менее 10,5 мкк/мл увеличивало риск кровотечения в 3,2 раза (1,2-8,7; ДИ 95%, р = 0,021).

Выводы

Выводы. Уровень Х фактора у пациентов с фибрилляцией предсердий имеет широкий диапазон колебаний. Снижение или превышение им референтных значений может влиять на риск развития малых кровотечений или инсульта соответственно.

Introduction

Introduction. Xa factor inhibitors are a significant treatment option for patients with atrial fibrillation, as they assist in reducing the risk of stroke. However, there has not been enough research into the levels of X-factor in these patients.

Aim

Aim. To assess the impact of blood clotting factor X on the risk of adverse drug events (ADEs) in patients receiving apixaban or rivaroxaban treatment.

Materials and methods

Materials and methods. The study involved 102 patients with atrial fibrillation who were administered Xa inhibitors: 56 received rivaroxaban and 46 received apixaban. Adverse drug reactions were documented, which were noted in the patient's medical records during drug administration. The concentration of the X factor was measured using photocolorimetry with reagents designed to determine the concentration of the factor X — AssaySense Human Factor X (FX) Chromogenic Activity Assay Kit (AssayPro, USA).

Results

Results. In patients receiving apixaban therapy, the X factor concentration was lower in 32.6% of cases and in 43.5% of patients, it was higher than the reference value. In contrast, in patients receiving rivaroxaban therapy, these indicators were lower in 26.8% of cases and higher in 51.8% of patients. Overall, according to the medical records, there were 37 adverse reactions in 29 patients, including 23 (41.1%) ADEs in 19 patients (33.9%) receiving rivaroxaban and 14 (30,4%) ADEs in 10 patients (21.7%) taking apixaban. The level of X factor was statistically significantly associated with the risk of stroke, with an AUC ROC of 0.720 and p-value of 0.05, and with minor bleeding, with an AUC ROC of 0.735 and p-value 0.003. An increase in the X factor level above 12.6 pg/mL increased the risk of stroke by 9.4-fold (95% CI: 1.9-74.3, p = 0.034), while a decrease below 10.5 pg/mL increased the risk of bleeding by 3.2-fold (95% CI: 1.2-8.7, p = 0.021).

Conclusion

Conclusion. The level of the X factor in individuals with atrial fibrillation exhibits a wide range of variability. Deviations from the reference values, either below or above, can significantly impact the risk of experiencing minor bleeding or suffering a stroke, respectively.

ПОАКрискинсульткровотеченияингибиторы Ха-фактораосложненияDOACriskstrokebleedingfactor Xa inhibitorscomplicationsReferencesRuff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. The Lancet. 2014;383(9921):955-962. https://doi.org/10.1016/S0140-6736(13)62343-0.Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. The Lancet. 2014;383(9921):955-962. https://doi.org/10.1016/S0140-6736(13)62343-0.Barakat AF, Jain S, Masri A, Alkukhun L, Senussi M, Sezer A et al. Outcomes of Direct Oral Anticoagulants in Atrial Fibrillation Patients Across Different Body Mass Index Categories. JACC Clin Electrophysiol. 2021;7(5):649-658. https://doi.org/10.1016/j.jacep.2021.02.002.Barakat AF, Jain S, Masri A, Alkukhun L, Senussi M, Sezer A et al. Outcomes of Direct Oral Anticoagulants in Atrial Fibrillation Patients Across Different Body Mass Index Categories. JACC Clin Electrophysiol. 2021;7(5):649-658. https://doi.org/10.1016/j.jacep.2021.02.002.Lip GYH, Noxon V, Kang A, Luo X, Atreja N, Han S et al. Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims. J Thromb Thrombolysis. 2024;57(6):1092-1102. https://doi.org/10.1007/s11239-024-02976-1.Lip GYH, Noxon V, Kang A, Luo X, Atreja N, Han S et al. Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims. J Thromb Thrombolysis. 2024;57(6):1092-1102. https://doi.org/10.1007/s11239-024-02976-1.Гераскина ЛА, Алиева ММ, Фонякин АВ, Максимова МЮ, Гарабова НИ, Буржунова МГ. Повторный ишемический инсульт при фибрилляции предсердий: частота, гетерогенность, профилактика. Атеротромбоз. 2020;(2):7-16. https://doi.org/10.21518/2307-1109-2020-2-7-16.Geraskina LA, Alieva MM, Fonyakin AV, Maximova MYu, Garabova NI, Burzhunova MG. Recurrent ischemic stroke in patients with atrial fibrillation: frequency, heterogeneity, prevention. Atherothrombosis. 2020;(2):7-16. (In Russ.) https://doi.org/10.21518/2307-1109-2020-2-7-16.Chao TF, Chan YH, Chiang CE, Tuan TC, Liao JN, Chen TJ et al. Stroke prevention with direct oral anticoagulants in high-risk elderly atrial fibrillation patients at increased bleeding risk. Eur Heart J Qual Care Clin Outcomes. 2022;8(7):730-738. https://doi.org/10.1093/ehjqcco/qcab076.Chao TF, Chan YH, Chiang CE, Tuan TC, Liao JN, Chen TJ et al. Stroke prevention with direct oral anticoagulants in high-risk elderly atrial fibrillation patients at increased bleeding risk. Eur Heart J Qual Care Clin Outcomes. 2022;8(7):730-738. https://doi.org/10.1093/ehjqcco/qcab076.Benz AP, Hohnloser SH, Eikelboom JW, Carnicelli AP, Giugliano RP, Granger CB et al. Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation. Eur Heart J. 2023;44(20):1807-1814. https://doi.org/10.1093/eurheartj/ehad200.Benz AP, Hohnloser SH, Eikelboom JW, Carnicelli AP, Giugliano RP, Granger CB et al. Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation. Eur Heart J. 2023;44(20):1807-1814. https://doi.org/10.1093/eurheartj/ehad200.Ip YMB, Lau KK, Ko H, Lau L, Yao A, Wong GLH et al. Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant. Neurology. 2023;101(4):Е358-Е369. https://doi.org/10.1212/WNL.00000000002O7422.Ip YMB, Lau KK, Ko H, Lau L, Yao A, Wong GLH et al. Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant. Neurology. 2023;101(4):Е358-Е369. https://doi.org/10.1212/WNL.00000000002O7422.Yang L, Brooks MM, Glynn NW, Zhang Y, Saba S, Hernandez I. Real-World Direct Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Medicare Beneficiaries With Atrial Fibrillation. Am J Cardiol. 2020;126:29-36. https//doi.org/10.1016/j.amjcard.2020.03.034.Yang L, Brooks MM, Glynn NW, Zhang Y, Saba S, Hernandez I. Real-World Direct Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Medicare Beneficiaries With Atrial Fibrillation. Am J Cardiol. 2020;126:29-36. https//doi.org/10.1016/j.amjcard.2020.03.034.Redondo M, Watzke HH, Stucki B, Sulzer I, Demarmels Biasiutti F, Binder BR et al. Coagulation Factors II, V, VII, and X, Prothrombin Gene 20210G→A Transition, and Factor V Leiden in Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 1999;19(4):1020-1025. https://doi.org/10.1161/01.ATV.19.4.1020.Redondo M, Watzke HH, Stucki B, Sulzer I, Demarmels Biasiutti F, Binder BR et al. Coagulation Factors II, V, VII, and X, Prothrombin Gene 20210G^A Transition, and Factor V Leiden in Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 1999;19(4):1020-1025. https://doi.org/10.1161/01.ATV.19.4.1020.Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000;342(10):696-701. https://doi.org/10.1056/NEJM200003093421004.Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000;342(10):696-701. https://doi.org/10.1056/NEJM200003093421004.Chandler WL, Rodgers GM, Sprouse JT, Thompson AR. Elevated Hemostatic Factor Levels as Potential Risk Factors for Thrombosis. Arch Pathol Lab Med. 2002;126(11):1405-1414. https://doi.org/10.5858/2002-126-1405-EHFLAP.Chandler WL, Rodgers GM, Sprouse JT, Thompson AR. Elevated Hemostatic Factor Levels as Potential Risk Factors for Thrombosis. Arch Pathol Lab Med. 2002;126(11):1405-1414. https://doi.org/10.5858/2002-126-1405-EHFLAP.Pastori D, Gazzaniga G, Farcomeni A, Bucci T, Menichelli D, Franchino G et al. Venous Thromboembolism in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis of 4,170,027 Patients. JACC Adv. 2023;2(7):100555. https://doi.org/10.1016/j.jacadv.2023.100555.Pastori D, Gazzaniga G, Farcomeni A, Bucci T, Menichelli D, Franchino G et al. Venous Thromboembolism in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis of 4,170,027 Patients. JACC Adv. 2023;2(7):100555. https://doi.org/10.1016/j.jacadv.2023.100555.Tan JL, Loh KP, Fortuna D, Ghaneie A. Anticoagulation in atrial fibrillation with factor X deficiency-A management dilemma. Clin Case Rep. 2018;6(9):1781-1785. https://doi.org/10.1002/ccr3.1731.Tan JL, Loh KP, Fortuna D, Ghaneie A. Anticoagulation in atrial fibrillation with factor X deficiency-A management dilemma. Clin Case Rep. 2018;6(9):1781-1785. https://doi.org/10.1002/ccr3.1731.Uprichard J, Perry DJ. Factor X deficiency. Blood Rev. 2002;16(2):97-110. Available at: https://pubmed.ncbi.nlm.nih.gov/12127953.Uprichard J, Perry DJ. Factor X deficiency. Blood Rev. 2002;16(2):97-110. Available at: https://pubmed.ncbi.nlm.nih.gov/12127953.Choufani EB, Sanchorawala V, Ernst T, Quillen K, Skinner M, Wright DG et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high- dose chemotherapy. Blood. 2001;97(6):1885-1887. https://doi.org/10.1182/blood.v97.6.1885.Choufani EB, Sanchorawala V, Ernst T, Quillen K, Skinner M, Wright DG et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high- dose chemotherapy. Blood. 2001;97(6):1885-1887. https://doi.org/10.1182/blood.v97.6.1885.Henson K, Files JC, Morrison FS. Transient acquired factor X deficiency: report of the use of activated clotting concentrate to control a life-threatening hemorrhage. Am J Med. 1989;87(5):583-585. https://doi.org/10.1016/s0002-9343(89)80618-7.Henson K, Files JC, Morrison FS. Transient acquired factor X deficiency: report of the use of activated clotting concentrate to control a life-threatening hemorrhage. Am J Med. 1989;87(5):583-585. https://doi.org/10.1016/s0002-9343(89)80618-7.Broze GJJr. An acquired, calcium-dependent, factor X inhibitor. Blood Cells Mol Dis. 2014;52(2-3):116-120. https://doi.org/10.1016/j.bcmd.2013.09.001.Broze GJJr. An acquired, calcium-dependent, factor X inhibitor. Blood Cells Mol Dis. 2014;52(2-3):116-120. https://doi.org/10.1016/j.bcmd.2013.09.001.Fair DS, Plow EF, Edgington TS. Combined functional and immunochemical analysis of normal and abnormal human factor X. J Clin Invest. 1979;64(4):884-894. https://doi.org/10.1172/JCI109554.Fair DS, Plow EF, Edgington TS. Combined functional and immunochemical analysis of normal and abnormal human factor X. J Clin Invest. 1979;64(4):884-894. https://doi.org/10.1172/JCI109554.Clemetson KJ. Chapter 9 Blood glycoproteins. In: Montreuil J, Vliegenthart JFG, Schachter H (eds). Glycoproteins II. 1st ed. Elsevier Science; 1997. Vol. 29, pp. 173-201. Available at: https://shop.elsevier.com/books/glycoproteins-ii/montreuil/978-0-444-82393-9.Clemetson KJ. Chapter 9 Blood glycoproteins. In: Montreuil J, Vliegenthart JFG, Schachter H (eds). Glycoproteins II. 1st ed. Elsevier Science; 1997. Vol. 29, pp. 173-201. Available at: https://shop.elsevier.com/books/glycoproteins-ii/montreuil/978-0-444-82393-9.Brown, MA, Stenberg LM, Stenflo J. Coagulation Factor Xa. Handbook of Proteolytic Enzymes. 2013;3:2908-2915.. https://doi.org/10.1016/b978-0-12-382219-2.00642-6.Brown, MA, Stenberg LM, Stenflo J. Coagulation Factor Xa. Handbook of Proteolytic Enzymes. 2013;3:2908-2915.. https://doi.org/10.1016/b978-0-12-382219-2.00642-6.Gedikli O, Altay S, Unlu S, Cakmak HA, Askin L, Yanik A et al. Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. Anatol J Cardiol. 2021;25(3):196-204. https://doi.org/10.5152/AnatolJCardiol.2021.57635.Gedikli O, Altay S, Unlu S, Cakmak HA, Askin L, Yanik A et al. Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. Anatol J Cardiol. 2021;25(3):196-204. https://doi.org/10.5152/AnatolJCardiol.2021.57635.Altay S, Yıldırımtürk Ö, Çakmak HA, Lütfü Aşkın, Ümit Yaşar Sinan, Feyzullah Beşli et al. New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study. Anatol J Cardiol. 2017;17(5):353-361. https://doi.org/10.14744/AnatolJCardiol.2016.7472.Altay S, Yıldırımtürk Ö, Çakmak HA, Lütfü Aşkın, Ümit Yaşar Sinan, Feyzullah Beşli et al. New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study. Anatol J Cardiol. 2017;17(5):353-361. https://doi.org/10.14744/AnatolJCardiol.2016.7472.Hammersley D, Signy M. Navigating the choice of oral anticoagulation therapy for atrial fibrillation in the NOAC era. Ther Adv Chronic Dis. 2017;8(12):165-176. https://doi.org/10.1177/2040622317720106.Hammersley D, Signy M. Navigating the choice of oral anticoagulation therapy for atrial fibrillation in the NOAC era. Ther Adv Chronic Dis. 2017;8(12):165-176. https://doi.org/10.1177/2040622317720106.Okumura Y, Yokoyama K, Matsumoto N, Tachibana E, Kuronuma K, Oiwa K et al. Three-Year Clinical Outcomes Associated With Warfarin vs. Direct Oral Anticoagulant Use Among Japanese Patients With Atrial Fibrillation - Findings From the SAKURA AF Registry. Circ J. 2018;82(10):2500-2509. https://doi.org/10.1253/circj.CJ-18-0535.Okumura Y, Yokoyama K, Matsumoto N, Tachibana E, Kuronuma K, Oiwa K et al. Three-Year Clinical Outcomes Associated With Warfarin vs. Direct Oral Anticoagulant Use Among Japanese Patients With Atrial Fibrillation - Findings From the SAKURA AF Registry. Circ J. 2018;82(10):2500-2509. https://doi.org/10.1253/circj.CJ-18-0535.Carbone A, Bottino R, D'Andrea A, Russo V. Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials. Biomedicines. 2023;11(1):131. https://doi.org/10.3390/biomedicines11010131.Carbone A, Bottino R, D'Andrea A, Russo V. Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials. Biomedicines. 2023;11(1):131. https://doi.org/10.3390/biomedicines11010131.Tormoen GW, Khader A, Gruber A, McCarty OJT. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor. Phys Bio. 2013;10(3). https://doi.org/10.1088/1478-3975/10/3/036003.Tormoen GW, Khader A, Gruber A, McCarty OJT. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor. Phys Bio. 2013;10(3). https://doi.org/10.1088/1478-3975/10/3/036003.Hooglugt A, Klatt O, Huveneers S. Vascular stiffening and endothelial dysfunction in atherosclerosis. Curr Opin Lipidol. 2022;33(6):353-363. https://doi.org/10.1097/MOL.0000000000000852.Hooglugt A, Klatt O, Huveneers S. Vascular stiffening and endothelial dysfunction in atherosclerosis. Curr Opin Lipidol. 2022;33(6):353-363. https://doi.org/10.1097/MOL.0000000000000852.Stark K, Massberg S. Interplay between inflammation and thrombosis in cardiovascular pathology. Nat Rev Cardiol. 2021;18(9):666-682. https://doi.org/10.1038/s41569-021-00552-1.Stark K, Massberg S. Interplay between inflammation and thrombosis in cardiovascular pathology. Nat Rev Cardiol. 2021;18(9):666-682. https://doi.org/10.1038/s41569-021-00552-1.Oikonomou E, Leopoulou M, Theofilis P, Antonopoulos AS, Siasos G, Latsios G et al. A link between inflammation and thrombosis in atherosclerotic cardiovascular diseases: Clinical and therapeutic implications. Atherosclerosis. 2020;309:16-26. https://doi.org/10.1016/j.atherosclerosis.2020.07.027.Oikonomou E, Leopoulou M, Theofilis P, Antonopoulos AS, Siasos G, Latsios G et al. A link between inflammation and thrombosis in atherosclerotic cardiovascular diseases: Clinical and therapeutic implications. Atherosclerosis. 2020;309:16-26. https://doi.org/10.1016/j.atherosclerosis.2020.07.027.Acampa M, Camarri S, Lazzerini PE, Guideri F, Tassi R, Valenti R et al. Increased arterial stiffness is an independent risk factor for hemorrhagic transformation in ischemic stroke undergoing thrombolysis. Int J Cardiol. 2017;243:466-470. https://doi.org/10.1016/j.ijcard.2017.03.129.Acampa M, Camarri S, Lazzerini PE, Guideri F, Tassi R, Valenti R et al. Increased arterial stiffness is an independent risk factor for hemorrhagic transformation in ischemic stroke undergoing thrombolysis. Int J Cardiol. 2017;243:466-470. https://doi.org/10.1016/j.ijcard.2017.03.129.

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