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REVIEW ARTICLE

An overview of the anticoagulation therapy in ischemic stroke associated with non-valvular atrial fibrillation

Yicong Wang1,2,3† ,  Ruinan Zhang1,2,3† ,  Yilong Wang1,2,3,4,5,6,7* ,  Hui Qu1,2,3*
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1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
2 National Center for Neurological Disorders, Beijing, China
3 China National Clinical Research Center for Neurological Diseases, Beijing, China
4 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
5 Chinese Institute for Brain Research, Beijing, China
6 Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China
7 Laboratory for Clinical Medicine, Capital Medical University Beijing, China
Brain & Heart, 4851 https://doi.org/10.36922/bh.4851
Submitted: 13 September 2024 | Revised: 1 December 2024 | Accepted: 6 December 2024 | Published: 30 December 2024
(This article belongs to the Special Issue The Brain Disorders with Left Atrium)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Atrial fibrillation (AF) significantly contributes to ischemic stroke, which poses a major healthcare challenge due to its significant morbidity and mortality rates. AF increases with age and is a common cause of cardioembolic strokes – a substantial economic and social burden in cerebrovascular disease management. The cornerstone of treatment for AF-related ischemic stroke lies in anticoagulation therapy. Current clinical evidence strongly supports the prolonged administration of warfarin or novel oral anticoagulants (NOACs) in non-valvular AF patients. Considering the practicality and their consistent blood levels in real-world settings, NOACs are opted over traditional therapies by an increasing number of patients; NOACs, such as apixaban and dabigatran showing promising effectiveness and lower bleeding risks compared to warfarin, an increasing number of patients are opting for NOACs over traditional therapies. Recent studies focus on determining the optimal timing for initiating anticoagulation post-stroke, as early intervention potentially reduces recurrence and complications. However, given the diverse clinical presentations of these patients, careful consideration must be given to the timing of anticoagulation initiation and the unique circumstances of special populations, including those with renal impairment, elderly adults, and patients with cerebral microbleeds. This comprehensive review delves into the complexities of anticoagulation management in AF-related ischemic stroke, with a particular focus on the optimal timing of oral anticoagulant initiation and tailored strategies for special patient subgroups. The ultimate goal of this review is to equip healthcare providers with valuable clinical insights and guidance to manage the challenges of AF-related ischemic stroke.

Keywords
Non-valvular atrial fibrillation
Ischemic stroke
Anticoagulation
Funding
This study was supported by grants from the National Natural Science Foundation of China (No. 82425101); Beijing Municipal Science and Technology Commission (No.Z2311000048230360); Capital’s Funds for Health Improvement and Research (2022-2-2045; National Key R&D Program of China (2024YFC3044800, 2022YFF1501500, 2022YFF1501501, 2022YFF1501502, 2022YFF1501503, 2022YFF1501504, 2022YFF1501505); Youth Beijing Scholar Program (No.010); Beijing Laboratory of Oral Health (PXM2021_014226_000041); Beijing Talent Project - Class A: Innovation and Development (No. 2018A12); National Ten- Thousand Talent Plan”- Leadership of Scientific and Technological Innovation; National Key R&D Program of China (No. 2017YFC1307900, 2017YFC1307905); Beijing Outstanding Young Scientist Program (No. BJJWZYJH01201910025030).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Bai Y, Wang YL, Shantsila A, Lip GYH. The global burden of atrial fibrillation and stroke: A systematic review of the clinical epidemiology of atrial fibrillation in Asia. Chest. 2017;152(4):810-820. doi: 10.1016/j.chest.2017.03.048

 

  1. Hankey GJ. Stroke. Lancet. 2017;389(10069):641-654. doi: 10.1016/S0140-6736(16)30962-X

 

  1. Kornej J, Börschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: Novel methods and new insights. Circ Res. 2020;127(1):4-20. doi: 10.1161/CIRCRESAHA.120.316340

 

  1. Kamel H, Healey JS. Cardioembolic stroke. Circ Res. 2017;120(3):514-526. doi: 10.1161/CIRCRESAHA.116.308407

 

  1. Cohen A, Donal E, Delgado V, et al. EACVI recommendations on cardiovascular imaging for the detection of embolic sources: Endorsed by the Canadian Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2021;22(6):e24-e57. doi: 10.1093/ehjci/jeab008

 

  1. Escudero-Martínez I, Morales-Caba L, Segura T. Atrial fibrillation and stroke: A review and new insights. Trends Cardiovasc Med. 2023;33(1):23-29. doi: 10.1016/j.tcm.2021.12.001

 

  1. Jame S, Barnes G. Stroke and thromboembolism prevention in atrial fibrillation. Heart. 2020;106(1):10-17. doi: 10.1136/heartjnl-2019-314898

 

  1. Klijn CJ, Paciaroni M, Berge E, et al. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline. Eur Stroke J. 2019;4(3):198-223. doi: 10.1177/2396987319841187

 

  1. 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): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498. doi: 10.1093/eurheartj/ehaa612

 

  1. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi: 10.1161/STR.0000000000000375

 

  1. Halperin JL, Hankey GJ, Wojdyla DM, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation. 2014;130(2):138-146. doi: 10.1161/CIRCULATIONAHA.113.005008

 

  1. López-López JA, Sterne JAC, Thom HHZ, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: Systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058. doi: 10.1136/bmj.j5058

 

  1. Carnicelli AP, Hong H, Connolly SJ, et al. Direct oral anticoagulants versus warfarin in patients with atrial fibrillation: Patient-level network meta-analyses of randomized clinical trials with interaction testing by age and sex. Circulation. 2022;145(4):242-255. doi: 10.1161/CIRCULATIONAHA.121.056355

 

  1. Steinberg BA, Gao H, Shrader P, et al. International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries. Am Heart J. 2017;194:132-140. doi: 10.1016/j.ahj.2017.08.011

 

  1. Ntaios G, Papavasileiou V, Diener HC, Makaritsis K, Michel P. Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials. Int J Stroke. 2017;12(6):589-596. doi: 10.1177/1747493017700663

 

  1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210

 

  1. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330-1393. doi: 10.1093/eurheartj/ehy136

 

  1. Seiffge DJ, Traenka C, Polymeris A, et al. Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events. Neurology. 2016;87(18):1856-1862. doi: 10.1212/WNL.0000000000003283

 

  1. Paciaroni M, Agnelli G, Falocci N, et al. Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: Effect of anticoagulation and its timing: The RAF study. Stroke. 2015;46(8):2175-2182. doi: 10.1161/STROKEAHA.115.008891

 

  1. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. doi: 10.1161/STR.0000000000000158

 

  1. Toyoda K, Arihiro S, Todo K, et al. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI-NVAF study. Int J Stroke. 2015;10(6):836-842. doi: 10.1111/ijs.12452

 

  1. De Marchis GM, Seiffge DJ, Schaedelin S, et al. Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: An observational study and individual patient data pooled analysis. J Neurol Neurosurg Psychiatry. 2022;93(2):119-125. doi: 10.1136/jnnp-2021-327236

 

  1. Kimura S, Toyoda K, Yoshimura S, et al. Practical “1-2-3- 4-Day” rule for starting direct oral anticoagulants after ischemic stroke with atrial fibrillation: Combined hospital-based cohort study. Stroke. 2022;53(5):1540-1549. doi: 10.1161/STROKEAHA.121.036695

 

  1. Oldgren J, Åsberg S, Hijazi Z, Wester P, Bertilsson M, Norrving B. Early versus delayed non-vitamin K Antagonist oral anticoagulant therapy after acute ischemic stroke in atrial fibrillation (TIMING): A registry-based randomized controlled noninferiority study. Circulation. 2022;146(14):1056-1066. doi: 10.1161/CIRCULATIONAHA.122.060666

 

  1. Fischer U, Koga M, Strbian D, et al. Early versus later anticoagulation for stroke with atrial fibrillation. N Engl J Med. 2023;388(26):2411-2421. doi: 10.1056/NEJMoa2303048

 

  1. Goeldlin MB, Hakim A, Branca M, et al. Early vs late anticoagulation in minor, moderate, and major ischemic stroke with atrial fibrillation: Post hoc analysis of the ELAN randomized clinical trial. JAMA Neurol. 2024;81(7):693-702. doi: 10.1001/jamaneurol.2024.1450

 

  1. Best JG, Arram L, Ahmed N, et al. Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial. Int J Stroke. 2022;17(5):583-589. doi: 10.1177/17474930211057722

 

  1. Werring DJ, Dehbi HM, Ahmed N, et al. Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): A multicentre, blinded-endpoint, phase 4, randomised controlled trial. Lancet. 2024 ;404:1731- 1741. doi: 10.1016/S0140-6736(24)02197-4

 

  1. King BT, Lawrence PD, Milling TJ, Warach SJ. Optimal delay time to initiate anticoagulation after ischemic stroke in atrial fibrillation (START): Methodology of a pragmatic, response-adaptive, prospective randomized clinical trial. Int J Stroke. 2019;14(9):977-982. doi: 10.1177/1747493019870651

 

  1. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104. doi: 10.1056/NEJMoa1310907

 

  1. Hohnloser SH, Fudim M, Alexander JH, et al. Efficacy and safety of Apixaban versus warfarin in patients with atrial fibrillation and extremes in body weight. Circulation. 2019;139(20):2292-2300. doi: 10.1161/CIRCULATIONAHA.118.037955

 

  1. Böhm M, Ezekowitz MD, Connolly SJ, et al. Changes in renal function in patients with atrial fibrillation: An analysis from the RE-LY trial. J Am Coll Cardiol. 2015;65(23):2481-2493. doi: 10.1016/j.jacc.2015.03.577

 

  1. Lau YC, Proietti M, Guiducci E, Blann AD, Lip GYH. Atrial fibrillation and thromboembolism in patients with chronic kidney disease. J Am Coll Cardiol. 2016;68(13):1452-1464. doi: 10.1016/j.jacc.2016.06.057

 

  1. Binding C, Blanche P, Lip GYH, et al. Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation. Eur Heart J Cardiovasc Pharmacother. 2024;10(3):210-218. doi: 10.1093/ehjcvp/pvae016

 

  1. Harrington J, Carnicelli AP, Hua K, et al. Direct oral anticoagulants versus warfarin across the spectrum of kidney function: Patient-level network meta-analyses from COMBINE AF. Circulation. 2023;147(23):1748-1757. doi: 10.1161/CIRCULATIONAHA.122.062752

 

  1. Kotalczyk A, Mazurek M, Kalarus Z, Potpara TS, Lip GYH. Stroke prevention strategies in high-risk patients with atrial fibrillation. Nat Rev Cardiol. 2021;18(4):276-290. doi: 10.1038/s41569-020-00459-3

 

  1. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014;6:213-220. doi: 10.2147/CLEP.S47385

 

  1. Caldeira D, Nunes-Ferreira A, Rodrigues R, Vicente E, Pinto FJ, Ferreira JJ. Non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis. Arch Gerontol Geriatr. 2019;81:209-214. doi: 10.1016/j.archger.2018.12.013

 

  1. Kato ET, Giugliano RP, Ruff CT, et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. J Am Heart Assoc. 2016;5(5):e003432. doi: 10.1161/JAHA.116.003432

 

  1. Chiang CE, Chao TF, Choi EK, et al. Stroke prevention in atrial fibrillation: A scientific statement of JACC: Asia (Part 2). JACC Asia. 2022;2(5):519-537. doi: 10.1016/j.jacasi.2022.06.004

 

  1. Kuroda M, Tamiya E, Nose T, et al. Effect of 15-mg edoxaban on clinical outcomes in 3 age strata in older patients with atrial fibrillation: A prespecified subanalysis of the ELDERCARE-AF randomized clinical trial. JAMA Cardiol. 2022;7(6):583-590. doi: 10.1001/jamacardio.2022.0480

 

  1. Polymeris AA, Macha K, Paciaroni M, et al. Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation. Ann Neurol. 2022;91(1):78-88. doi: 10.1002/ana.26267

 

  1. Duering M, Biessels GJ, Brodtmann A, et al. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023;22(7):602-618. doi: 10.1016/S1474-4422(23)00131-X

 

  1. Horstmann S, Möhlenbruch M, Wegele C, et al. Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur J Neurol. 2015;22(10):1355-1362. doi: 10.1111/ene.12608

 

  1. Wilson D, Ambler G, Shakeshaft C, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): A multicentre observational cohort study. Lancet Neurol. 2018;17(6):539-547. doi: 10.1016/S1474-4422(18)30145-5

 

  1. Choi KH, Kim JH, Lee C, et al. Microbleeds and outcome in patients with acute ischemic stroke and atrial fibrillation taking anticoagulants. Stroke. 2020;51(12):3514-3522.doi: 10.1161/STROKEAHA.120.030300

 

  1. Yokoyama M, Mizuma A, Terao T, et al. Effectiveness of nonvitamin K antagonist oral anticoagulants and warfarin for preventing further cerebral microbleeds in acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one microbleed: CMB-NOW multisite pilot trial. J Stroke Cerebrovasc Dis. 2019;28(7):1918-1925. doi: 10.1016/j.jstrokecerebrovasdis.2019.03.050
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