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Should patients treated with direct oral anticoagulants receive intravenous thrombolytics for acute ischaemic stroke?

BMJ 2024; 387 doi: https://doi.org/10.1136/bmj-2024-079322 (Published 24 October 2024) Cite this as: BMJ 2024;387:e079322

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Practical Prescribing: Direct oral anticoagulants
  1. Faizan Khan, postdoctoral research fellow1,
  2. Thomas Meinel, clinician, scientist in interdisciplinary stroke medicine2,
  3. Ronda Lun, vascular neurology fellow1 3,
  4. Amy Y X Yu, stroke neurologist4,
  5. Bruce C V Campbell, professor of neurology5
  1. 1Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  2. 2Department of Neurology, Inselspital (Bern University Hospital) and University of Bern, Bern, Switzerland
  3. 3Division of Vascular Neurology, Stanford Healthcare, Palo Alto, CA, USA
  4. 4Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, ON, Canada
  5. 5Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia
  1. Correspondence to: F Khan faizan.khan1{at}ucalgary.ca

What you need to know

  • Intravenous thrombolytics are not recommended for acute ischaemic stroke in patients who have taken a direct oral anticoagulant (DOAC) within 48 hours before presentation because of the perceived higher risk of intracranial haemorrhage.

  • The safety of intravenous thrombolytics in this setting is not known because of a paucity of data from adequately powered randomised controlled trials; emerging data of low quality do not show a higher risk of intracranial haemorrhage after thrombolysis in selected patients taking DOACs compared with those not receiving anticoagulant treatment.

  • Evaluate clinical and imaging characteristics and consider alternative treatments, such as direct endovascular thrombectomy, to determine the risks and benefits for each patient. When available, measuring DOAC plasma levels or reversing DOAC treatment might help individualise decisions about the use of intravenous thrombolytics.

Intravenous thrombolytics, including the recombinant tissue plasminogen activators alteplase or tenecteplase, are the standard treatment for acute ischaemic stroke. They aim to reperfuse the ischaemic brain and reduce disability in eligible patients.1 The main criteria for thrombolysis are that the treatment can be administered within 4.5 hours of the onset of stroke symptoms and that there is no intracranial haemorrhage confirmed by imaging before treatment.23456

About 18% of patients who have an acute ischaemic stroke and might qualify for thrombolysis are also taking direct oral anticoagulants (DOACs) such as factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) or the thrombin inhibitor, dabigatran.7 Common indications for treatment with DOACs include stroke prevention in atrial fibrillation, treatment of venous thromboembolism, and coronary and peripheral atherosclerotic disease.8

According to guidelines from the American Heart Association/American Stroke Association and the European Stroke Organization, treatment with DOACs within the past 48 hours is a contraindication for thrombolysis because of the perceived higher risk of intracranial haemorrhage.45 Although other international …

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