When to initiate Direct Oral Anticoagulants (DOACs) in post-stroke patients?

From the Guidelines

Direct Oral Anticoagulants (DOACs) should be initiated 1-14 days after an acute ischemic stroke, depending on the stroke severity, with the exact timing tailored to each patient's specific situation, as recommended by the 2018 European Heart Rhythm Association practical guide 1. When considering the initiation of DOACs in post-stroke patients, several factors must be taken into account, including the severity of the stroke, the risk of recurrent stroke, and the risk of hemorrhagic transformation.

• For minor strokes, DOACs can be started as early as 1-3 days post-stroke,
• while for more severe strokes, it's often prudent to wait 1-2 weeks,
• with the specific timing guided by repeat brain imaging to determine the optimal initiation of anticoagulation in patients with a large stroke at risk for hemorrhagic transformation, as suggested by the 2016 ESC guidelines for the management of atrial fibrillation 1. The choice of DOAC, including apixaban, rivaroxaban, dabigatran, and edoxaban, should also be tailored to each patient's specific situation, taking into account their individual risk factors and comorbidities.
• It's crucial to ensure that the patient has no contraindications to anticoagulation and that neuroimaging has confirmed the absence of intracranial hemorrhage before initiating therapy,
• and to weigh the benefits of anticoagulation against the risks of bleeding, particularly in the first days after a large stroke, as noted in the 2018 European Heart Rhythm Association practical guide 1. In cases of cardioembolic stroke due to atrial fibrillation, earlier initiation of DOACs may be considered if the benefit outweighs the risk of bleeding, with the decision guided by the individual patient's risk profile and the results of repeat brain imaging.
• The use of 'bridging' anticoagulation with heparin is not recommended due to the rapid onset of action of DOACs and the associated risk of bleeding,
• and instead, the initiation of DOACs should be guided by the patient's clinical status and the results of neuroimaging, as recommended by the 2018 European Heart Rhythm Association practical guide 1.

From the Research

Timing of Direct Oral Anticoagulants (DOACs) Initiation

• The optimal time to initiate DOACs after an acute ischemic stroke in patients with atrial fibrillation is uncertain 2.
• Parenteral anticoagulation within 48 hours is associated with an increased risk of hemorrhagic transformation and is not recommended 2.
• Insufficient data exist to support the safety of routine oral anticoagulant (DOACs or warfarin) initiation within 48 hours of an acute ischemic stroke 2.
• Direct oral anticoagulant initiation within 2 days of an acute ischemic stroke is associated with a 5% rate of hemorrhagic transformation 2.

Stroke Severity and DOACs Initiation

• Infarct size and presence of hemorrhage are important factors in identifying the optimal time to initiate DOACs and should guide decisions when available 2.
• Early DOAC initiation within 1,2,3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding 3.
• A "1-2-3-4-day" rule for starting DOACs after ischemic stroke with atrial fibrillation may be a practical approach, with the timing of initiation depending on stroke severity 3.

Comparison of DOACs and Warfarin

• DOACs have been shown to have a better prognosis than warfarin after ischemic stroke, with a lower risk of mortality and bleeding complications 4.
• Apixaban and edoxaban, in particular, have been found to have a lower risk of death after ischemic stroke compared to other DOACs 4.
• DOACs are preferred over warfarin by stroke neurologists for secondary stroke prevention in patients with atrial fibrillation, due to their strategic dosage and lack of need for periodic prothrombin-time testing 5.

Clinical Implications

• The choice and timing of anticoagulation for secondary stroke prevention in patients with atrial fibrillation remain uncertain and require further study 5.
• More research is needed to clarify the optimal timing of DOAC initiation after an acute ischemic stroke and to establish the safety and efficacy of DOACs in different patient populations 2, 6.