DOACs and bleeding: the role of antidotes

The use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation is associated with the risk of bleeding complications. To manage severe and life-threatening bleeding, specific antidotes have become available that can effectively restore haemostasis.

Major bleeding in patients with atrial fibrillation medicated with factor Xa (FXa) and factor IIa (FIIa) inhibitors is still a concern. The major limitation was the lack of specific reversal agents. However, antidotes have now become available and Dr Kaveshree Govender (Milpark Hospital, South Africa) presented their role in managing bleeding complications [1].

The 2018 EHRA practical guideline on atrial fibrillation provided guidance on managing bleeding episodes in DOAC-treated patients: delay or discontinuation of DOAC treatment in mild bleeding, symptomatic treatment in non-life-threatening major bleeding with or without antidote-treatment, and finally antidote-treatment in life-threatening bleeding events.

Available antidotes for DOACs have been introduced:

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  • Anti-fibrinolytic agents, which are readily available at low costs, show low thrombogenicity and were recommended by the 2018 EHRA guideline.
  • Off-label use of haemostatic agents (i.e. activated prothrombin complex concentrate for dabigatran-associated bleeding and 4-factor prothrombin complex concentrate for FXa inhibitor-associated bleeding).
  • Non-specific agents, which currently lack the support of good-quality clinical studies.
  • Andexanet alpha, a specific antidote for FXa inhibitor-associated bleeding.
  • Idarucizumab, a specific antidote for dabigatran-associated bleeding.

Specific agents are less readily available and are costly and should primarily be used for life-threatening bleeding and for urgent invasive procedures in DOAC-treated patients.

Dr Govender concluded that DOAC-associated bleeding should be risk-stratified to determine burden management. Moderate or life-threatening bleeding requires temporary discontinuation of the drug and supportive care. Specific antidotes are less readily available and are costly but show good efficacy and should be used for life-threatening bleeding and for urgent invasive procedures in DOAC-treated patients. If unavailable, non-specific agents are best considered in severe bleeding, but there is a lack of evidence for both safety and efficacy.

1. 
   
   1. Govender K. Oral anticoagulant and bleeding: role of antidotes. 2021 EHRA Congress, 23-25 April.

 



Posted on 25 April, 202116 June, 2021