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Tutorial

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Poll

Which of these recent studies will impact your management of DOAC-ICH the most?

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ANNEXA-I study of andexanet alfa in DOAC-ICH
   
INTERACT4 study of early BP control in ICH
   
ENRICH & SWITCH studies of utility of surgery in ICH
   
Another recent study in ICH
   

Tutorial

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Poll

Which of these regional guidelines do you follow for the management of DOAC-ICH?

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ASA/AHA 2022 and/or ACC 2020
   
APSC 2021
   
ESO 2019
   
Other guidelines/a combination/do not follow guidelines/not applicable
   

Tutorial

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Poll

Which of these DOAC reversal agents are available for use in your institution?

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4F-PCC, andexanet alfa and idarucizumab
   
4F-PCC and andexanet alfa
   
4F-PCC and idarucizumab
   
Only one agent/other combination
   

Tutorial

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Poll

In your experience, what is the mortality rate in patients you see with ICH?

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<25%
   
25–50%
   
>50–75%
   
>75%
   
 
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Stroke, Neurosurgery CE/CME accredited

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Intracranial haemorrhage related to direct oral anticoagulant medications: Latest evidence for reversal strategies

  • A practice aid is available for this activity in the Toolkit
  • Downloads including slides are available for this activity in the Toolkit
Learning Objectives

After watching this activity, participants should be better able to:

  • Recognize the risk of intracranial haemorrhage (ICH) in the era of direct oral anticoagulant (DOAC) therapy
  • Evaluate the latest clinical efficacy and safety data for approved reversal strategies in patients with DOAC-ICH
  • Outline the recommended guidelines on the management of DOAC-ICH
Overview

In this activity, Prof. Dr. med. Jan Beyer-Westendorf addresses the issue of reversal strategies in patients with direct oral anticoagulant-associated intracranial haemorrhage (DOAC-ICH), including benefits and risks of DOAC use, evidence for DOAC reversal agents and guideline-directed management of the condition.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of critical care/emergency medicine physicians, neurologists, neurosurgeons and pharmacists involved in the management of intracranial haemorrhage.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Dr. med. Jan Beyer-Westendorf discloses Advisory board or panel fees from Alexion/AstraZeneca, Bayer and Daiichi Sankyo. Grants/research support from Alexion/AstraZeneca, Bayer, Daiichi Sankyo and LEO Pharma.

Content reviewer

Danielle Walker, DNP, APRN, AGNP-C has no relevant financial interests/relationships to disclose.

Touch Medical Directors

Hannah Fisher and Sola Neunie have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 05 August 2024. Date credits expire: 05 August 2025.

If you have any questions regarding credit please contact cpdsupport@usf.edu

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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Topics covered in this activity

Stroke / Neurosurgery
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touchTALKS
Intracranial haemorrhage related to direct oral anticoagulant medications: Latest evidence for reversal strategies
1.0 CE/CME credit

Question 1/4
According to data from a 2017 meta-analysis of phase III trials in patients with atrial fibrillation, what proportion of those taking DOAC therapy experienced an ICH?

DOAC, direct oral anticoagulant; ICH, intracranial haemorrhage.

In a 2017 meta-analysis of phase III RCTs that assessed the efficacy and safety of non-VKA OACs vs warfarin in patients with atrial fibrillation and a history of stroke/TIA, 1.0% (89/8,657) of patients taking non-VKA OACs experienced an ICH, compared with 1.9% (165/8,642) of patients in the warfarin group.1 The non-VKAs included in these studies were the direct OACs apixaban, dabigatran, edoxaban and rivaroxaban.1,2

Abbreviations

ICH, intracranial haemorrhage; OAC, oral anticoagulant; RCT, randomized controlled trial; TIA, transient ischaemic attack; VKA, vitamin K antagonist.

References

  1. Ntaios G, et al. Int J Stroke. 2017;12:589–96.
  2. Heestermans M, et al. Cells. 2022;11:3214.
Question 2/4
You have treated a patient with 4F-PCC after she experienced an ICH while on DOAC therapy. How would you counsel her husband, who has asked you about the risks associated with this treatment?

4F-PCC, four-factor prothrombin complex concentrate; DOAC, direct oral anticoagulant; ICH, intracranial haemorrhage.

In a 2022 meta-analysis of adults with ICH receiving treatment with a DOAC, 22 studies that included 967 patients treated with 4F-PCC for DOAC reversal were assessed. Among those receiving 4F-PCC, the thromboembolic event rate was 8% and the all-cause mortality rate was 26%.1 

These data are supported by the results of the ANNEXA-I trial, in which patients who had taken factor Xa inhibitors within 15 hours prior to an acute ICH received either andexanet alfa or usual care. Of those in the efficacy population receiving usual care (n=228), 86% (n=195) received PCC within 3 hours of randomization. Thrombotic events occurred in 6% of patients and death in 26% in the usual care group (extended population, n=267).2

Abbreviations

4F-PCC, four-factor PCC; DOAC, direct oral anticoagulant; ICH, intracranial haemorrhage; PCC, prothrombin complex concentrate.

References

  1. Chaudhary R, et al. JAMA Netw Open. 2022;5:e2240145.
  2. Connolly SJ, et al. N Engl J Med. 2024;390:1745–55.
Question 3/4
A 72-year-old female presents to the emergency room with a suspected ischaemic stroke. She has a history of atrial fibrillation and has been taking apixaban therapy, with the last dose taken 9 hours ago. Having confirmed an ICH with a CT scan, which guideline-directed agent would you consider to best reverse the anticoagulant effects?

4F-PCC, four-factor prothrombin complex concentrate; CT, computed tomography; ICH, intracranial haemorrhage.

AHA/ASA 2022, APSC 2021, ACC 2020 and ESO 2019 guidelines all recommend that in patients with OAC-associated bleeding/OAC-ICH taking apixaban therapy, anticoagulation should be reversed with andexanet alfa, or with PCC if andexanet alfa is not available.1–4

Abbreviations

ACC, American College of Cardiology; AHA, American Heart Association; APSC, Asian Pacific Society of Cardiology; ASA, American Stroke Association; ESO, European Stroke Association; ICH, intracranial haemorrhage; OAC, oral anticoagulant; PCC, prothrombin complex concentrate.

References

  1. Greenberg SM, et al. Stroke. 2022;53:e282–361.
  2. Chong DTT, et al. Eur Cardiol. 2021;16:e23.
  3. Tomaselli GF, et al. J Am Coll Cardiol. 2020;76:594–622.
  4. Christensen H, et al. Eur Stroke J. 2019;4:294–306.
Question 4/4
Your 72-year-old female patient with a history of atrial fibrillation and confirmed DOAC-ICH was treated with an apixaban reversal agent 5 days ago and is now recovering in hospital. After consulting with your multidisciplinary colleagues, which of these guideline-directed steps would you take to help prevent thromboembolic events and reduce all-cause mortality in this patient?

DOAC, direct oral anticoagulant; ICH, intracranial haemorrhage.

AHA/ASA 2022 guidelines recommend that, in patients with nonvalvular atrial fibrillation and OAC-ICH, resuming anticoagulation to prevent thromboembolic events and reduce all-cause mortality should be based on weighing benefit and risk. Left atrial appendage closure may be considered to reduce the risk of thromboembolic events in such patients if they are deemed ineligible for anticoagulation.1

Similarly, the ACC 2020 decision pathway recommends that the decision to restart anticoagulation in patients with OAC-associated bleeding should involve assessing the risk of a thromboembolic event (e.g. using the CHA2DS2-VASc score); considering the sequelae associated with thromboembolic events (e.g. higher mortality for ischaemic strokes with atrial fibrillation); as well as considering the net benefit of anticoagulation reinitiation in certain types of bleeds.2

Abbreviations

ACC, American College of Cardiology; AHA, American Heart Association; ASA, American Stroke Association; ICH, intracranial haemorrhage; OAC, oral anticoagulant.

References

  1. Greenberg SM, et al. Stroke. 2022;53:e282–361.
  2. Tomaselli GF, et al. J Am Coll Cardiol. 2020;76:594–622.
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