Reperfusion Strategy in Patients With Acute Ischemic Stroke Receiving Anticoagulant Therapy

Background. Atrial fibrillation is one of the leading causes of cardioembolic acute ischemic stroke and a major indication for long-term anticoagulant therapy. In patients who develop acute ischemic stroke while receiving anticoagulants, the selection of a reperfusion strategy is complicated by the need for rapid decision-making within a limited therapeutic time window, the potential risk of hemorrhagic complications, and the inability in some cases to promptly assess clinically relevant residual anticoagulant activity.

Objective. To summarize current evidence on the selection of a reperfusion strategy in patients with acute ischemic stroke receiving vitamin K antagonists or direct oral anticoagulants, with a focus on the safety of intravenous thrombolysis, laboratory assessment of anticoagulant status, reversal of anticoagulant effect, and the role of endovascular thrombectomy.

Key Content and Findings. In patients receiving vitamin K antagonists, the international normalized ratio remains the key laboratory criterion for determining eligibility for intravenous thrombolysis. In patients treated with direct oral anticoagulants, decision-making should take into account the specific drug, time since last intake, renal function, availability of specific laboratory assays, and individual hemorrhagic risk. Contemporary observational data suggest that intravenous thrombolysis may be safe in carefully selected patients with recent direct oral anticoagulant intake; however, the absence of randomized trials and universally accepted laboratory thresholds requires cautious interpretation of these findings. Reversal of anticoagulant effect may be considered in selected clinical scenarios, but it should not be regarded as a universal approach to expanding eligibility for thrombolytic therapy. In patients with large-vessel occlusion, endovascular thrombectomy remains a key reperfusion strategy and should not be delayed for clarification of anticoagulant status.

Conclusions. The available evidence supports the development of locally adapted algorithms for selecting a reperfusion strategy in patients with acute ischemic stroke receiving anticoagulant therapy. Such algorithms should aim to reduce time to reperfusion, decrease variability in clinical decision-making, and avoid inappropriate withholding of effective reperfusion therapy.

1. Singer D.E., Ziegler P.D., Koehler J.L., Sarkar S., Passman R.S. Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke. JAMA Cardiol, 2021, vol. 6, no. 12, pp. 1364-1369. doi:10.1001/jamacardio.2021.3702.

2. GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol, 2024, vol. 23, no. 10, pp. 973-1003. doi:10.1016/S1474-4422(24)00369-7.

3. Ministerstvo zdravookhraneniya Respubliki Belarus’. Klinicheskiy protokol “Diagnostika i lechenie patsientov s zabolevaniyami nervnoy sistemy (vzrosloe naselenie)” [Clinical protocol “Diagnosis and treatment of patients with diseases of the nervous system (adult population)”]. Utverzhden postanovleniem Ministerstva zdravookhraneniya Respubliki Belarus’ No. 8 ot 18 yanvarya 2018 g. [Approved by Resolution of the Ministry of Health of the Republic of Belarus No. 8 of 18 January 2018]. Minsk, 2018, 126 p. (in Russian).

4. Diaz H., Mouyal S., Zuber M., et al. Thirty years of intravenous thrombolysis for acute ischemic stroke: Historical perspectives, evidence from randomized trials, and emerging directions. Med, 2026, vol. 7, no. 1, 100888. doi:10.1016/j.medj.2025.100888.

5. Ageno W., Caramelli B., Donadini M.P., Girardi L., Riva N. Changes in the landscape of anticoagulation: a focus on direct oral anticoagulants. Lancet Haematol, 2024, vol. 11, no. 12, pp. e938-e950. doi:10.1016/S2352-3026(24)00281-3.

6. Jennings I., Kitchen D. Laboratory and Point of Care Monitoring of Vitamin K Antagonist Treatment. Handb Exp Pharmacol. Published online 30 December 2025. doi:10.1007/164_2025_782.

7. Willekens G., Studt J.D., Mendez A., et al. Auniversal anti-Xa assay for rivaroxaban, apixaban, and edoxaban measurements: method validation, diagnostic accuracy and external validation. Br J Haematol, 2021, vol. 193, no. 6, pp. 1203-1212. doi:10.1111/bjh.17470.

8. Tomaselli G.F., Mahaffey K.W., Cuker A., et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol, 2020, vol. 76, no. 5, pp. 594-622. doi:10.1016/j.jacc.2020.04.053.

9. Mega J.L., Simon T. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments. Lancet, 2015, vol. 386, no. 9990, pp. 281-291. doi:10.1016/S0140-6736(15)60243-4.

10. Verheugt F.W.A., Ten Berg J.M., Storey R.F., Cuisset T., Granger C.B. Antithrombotics: From Aspirin to DOACs in Coronary Artery Disease and Atrial Fibrillation (Part 3/5). J Am Coll Cardiol, 2019, vol. 74, no. 5, pp. 699-711. doi:10.1016/j.jacc.2019.02.080.

11. Demaerschalk B.M., Kleindorfer D.O., Adeoye O.M., et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/ American Stroke Association. Stroke, 2016, vol. 47, no. 2, pp. 581-641. doi:10.1161/STR.0000000000000086.

12. Yaghi S., Willey J.Z., Cucchiara B., et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 2017, vol. 48, no. 12, pp. e343-e361. doi:10.1161/STR.0000000000000152.

13. Prabhakaran S., Gonzalez N.R., Zachrison K.S., et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online 26 January 2026. doi:10.1161/STR.0000000000000513.

14. Berge E., Whiteley W., Audebert H., et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J, 2021, vol. 6, no. 1, pp. I-LXII. doi:10.1177/2396987321989865.

15. Yoshimura S. Medical Management of Acute Stroke based on Japan Stroke Society Guidelines and the Japan Stroke Data Bank. J Atheroscler Thromb, 2024, vol. 31, no. 12, pp. 1652-1659. doi:10.5551/jat.RV22027.

16. Meinel T.R., Wilson D., Gensicke H., Scheitz J.F., Ringleb P., Goganau I., Kaesmacher J., Bae H.J., Kim D.Y., Kermer P., et al.; International DOAC-IVT, TRISP, and CRCS-K-NIH Collaboration. Intravenous thrombolysis in patients with ischemic stroke and recent ingestion of direct oral anticoagulants. JAMA Neurol, 2023, vol. 80, pp. 233-243. doi:10.1001/jamaneurol.2022.4782.

17. Kam W., Holmes D.N., Hernandez A.F., Saver J.L., Fonarow G.C., Smith E.E., Bhatt D.L., Schwamm L.H., Reeves M.J., Matsouaka R.A., et al. Association of recent use of non-vitamin K antagonist oral anticoagulants with intracranial hemorrhage among patients with acute ischemic stroke treated with alteplase. JAMA, 2022, vol. 327, pp. 760-771. doi:10.1001/jama.2022.0948.

18. Boehme C., Mayer-Suess L., Mikšová D., Lang W., Knoflach M., Kiechl S.; Austrian Stroke Unit Registry Collaborators. Prime time for a trial assessing safety of intravenous thrombolysis in patients treated with direct oral anticoagulants. Stroke, 2024, vol. 55, pp. e149-e150. doi:10.1161/STROKEAHA.123.046142.

19. Bücke P., Jung S., Kaesmacher J., Goeldlin M.B., Horvath T., Prange U., Beyeler M., Fischer U., Arnold M., Seiffge D.J., et al. Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: a target trial analysis after the liberalization of institutional guidelines. Eur Stroke J, 2024, vol. 9, pp. 959-967. doi:10.1177/23969873241252751.

20. Matusevicius M., Säflund M., Balestrino M., et al. Intravenous thrombolysis in patients taking direct oral anticoagulation treatment before stroke onset: results from the Safe Implementation of Treatments in Stroke International Stroke Registry. Ann Neurol, 2025, vol. 97, no. 6, pp. 1205-1214. doi:10.1002/ana.27189.

21. Meinel T.R., Bücke P., D’Anna L., et al. Intravenous Thrombolysis in Patients With Recent Intake of Direct Oral Anticoagulants: A Target Trial Analysis and Comparison With Reversal Agent Use. Stroke, 2025, vol. 56, no. 10, pp. 2836-2845. doi:10.1161/STROKEAHA.125.051384.

22. Gerner S.T., Braemer A., Juenemann M.B., et al. Urine-based point-of-care detection of direct oral anticoagulant activity in acute stroke-accuracy at anti-Xa thresholds relevant for intravenous thrombolysis. Res Pract Thromb Haemost, 2025, vol. 10, no. 1, 103331. Published online 29 December 2025. doi:10.1016/j.rpth.2025.103331.

23. Levy J.H., Shaw J.R., Castellucci L.A., et al. Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost, 2024, vol. 22, no. 10, pp. 2889-2899. doi:10.1016/j.jtha.2024.07.009.

24. van Es N., De Caterina R., Weitz J.I. Reversal agents for current and forthcoming direct oral anticoagulants. Eur Heart J, 2023, vol. 44, no. 20, pp. 1795-1806. doi:10.1093/eurheartj/ehad123.

25. Barber P.A., Wu T.Y., Ranta A. Stroke reperfusion therapy following dabigatran reversal with idarucizumab in a national cohort. Neurology, 2020, vol. 94, no. 19, pp. e1968-e1972. doi:10.1212/WNL.0000000000009155.

26. Connolly S.J., Sharma M., Cohen A.T., et al. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. N Engl J Med, 2024, vol. 390, no. 19, pp. 1745-1755. doi:10.1056/NEJMoa2313040.

27. Panos N.G., Jones G.M., Cook A.M., et al. Reversal of Factor Xa Inhibitor-Related Intracranial Hemorrhage: A Multicenter, Retrospective, Observational Study Comparing the Efficacy and Safety of Andexanet and Prothrombin Complex Concentrates. Crit Care Med, 2025, vol. 53, no. 6, pp. e1202-e1213. doi:10.1097/CCM.0000000000006656.

28. Kristoffersen E.S., Seiffge D.J., Meinel T.R. Intravenous thrombolysis and mechanical thrombectomy in acute stroke patients on direct oral anticoagulants. J Neurol, 2024, vol. 272, no. 1, 82. Published online 21 December 2024. doi:10.1007/s00415-024-12832-0.

29. Seiffge D.J., Meinel T., Purrucker J.C., et al. Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants. J Neurol Neurosurg Psychiatry, 2021, vol. 92, no. 5, pp. 534-541. doi:10.1136/jnnp-2020-325456.

30. Mac Grory B., Holmes D.N., Matsouaka R.A., et al. Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke. JAMA, 2023, vol. 329, no. 23, pp. 2038-2049. doi:10.1001/jama.2023.8073.