How soon after a stroke should anticoagulation with medications like Eliquis (apixaban) or Xarelto (rivaroxaban) be started?

Timing of Anticoagulation After Stroke

The optimal timing for starting anticoagulants like Eliquis (apixaban) or Xarelto (rivaroxaban) after a stroke should follow the "1-3-6-12 day rule" based on stroke severity, with anticoagulation initiated at 1 day for TIA, 3 days for mild stroke, 6 days for moderate stroke, and 12 days for severe stroke. 1, 2

Timing Based on Stroke Severity

• Transient Ischemic Attack (TIA): Start anticoagulation 1 day after the event, after confirming absence of intracranial hemorrhage with imaging 1, 2
• Mild Stroke: Start anticoagulation after 3 days 1, 2
• Moderate Stroke: Start anticoagulation after 6 days 1, 2
• Severe Stroke: Start anticoagulation after 12 days 1, 2

Rationale and Evidence

• Early anticoagulation (within 48 hours) after ischemic stroke is not recommended due to increased risk of symptomatic intracranial hemorrhage 1
• Delayed anticoagulation beyond 14 days may increase risk of recurrent ischemic stroke 2, 3
• The European Society of Cardiology (ESC) recommends that in patients with AF who suffer a moderate-to-severe ischemic stroke, anticoagulation should be interrupted for 3-12 days based on multidisciplinary assessment of acute stroke and bleeding risk 1

Recent Evidence

• A 2022 Japanese and European cohort study proposed a more practical "1-2-3-4 day rule" with DOACs started at 1 day for TIA, 2 days for mild stroke, 3 days for moderate stroke, and 4 days for severe stroke, showing decreased risk of recurrent stroke without increased bleeding risk 4
• The OPTIMAS trial is investigating whether early DOAC treatment (within 4 days) is as effective or better than delayed initiation (7-14 days) in AF patients with acute ischemic stroke 5, 6

Important Considerations

• Repeat brain imaging (CT or MRI) is recommended before starting anticoagulation in patients with moderate or severe stroke to rule out hemorrhagic transformation 1, 2
• NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) are preferred over vitamin K antagonists in AF patients with previous stroke due to lower risk of intracranial hemorrhage 1, 2
• Bridging with heparin or low molecular weight heparin is not recommended during the acute phase of ischemic stroke 1, 2
• Aspirin may be considered for prevention of secondary stroke until the initiation of oral anticoagulation 1

Risk Assessment

• Factors increasing risk of hemorrhagic transformation include:

  • Large infarct size 2, 7
  • Presence of cerebral microbleeds 7
  • Prior thrombolytic therapy 7
  • Uncontrolled hypertension 1

• In patients at high risk of hemorrhagic conversion, it is reasonable to delay initiation of oral anticoagulation beyond 14 days 1

Long-term Management

• Long-term oral anticoagulation is strongly indicated as secondary prevention in AF patients after ischemic stroke 1
• NOACs are recommended in preference to vitamin K antagonists or aspirin in AF patients with a previous stroke 1
• After initiation, combination therapy of oral anticoagulant and an antiplatelet is not recommended 1