Timing of DOAC Resumption After Ischemic Stroke
Resume DOACs between 1-14 days after ischemic stroke in patients with atrial fibrillation, with the specific timing determined by stroke severity using the NIHSS score: 1 day for TIA, 3 days for mild stroke (NIHSS <8), 6-8 days for moderate stroke (NIHSS 8-15), and 12-14 days for severe stroke (NIHSS ≥16). 1, 2
Stroke Severity-Based Algorithm
The timing of DOAC resumption follows a structured approach based on stroke severity 1, 2:
Transient Ischemic Attack (TIA): Resume DOACs 1 day after the event, once intracranial hemorrhage is excluded by CT or MRI 1, 2
Mild Stroke (NIHSS <8): Resume DOACs 3 days after stroke onset, with repeat brain imaging at day 6 to evaluate for hemorrhagic transformation before initiating anticoagulation 1, 2
Moderate Stroke (NIHSS 8-15): Resume DOACs 6-8 days after stroke onset, with repeat brain imaging at day 6 to assess for hemorrhagic transformation 1, 2
Severe Stroke (NIHSS ≥16): Resume DOACs 12-14 days after stroke onset, with repeat brain imaging at day 12 to exclude hemorrhagic transformation 1, 2
Critical Safety Considerations
Never initiate anticoagulation within 48 hours of acute ischemic stroke, as this increases the risk of symptomatic intracranial hemorrhage without net benefit 1, 2. This applies to both DOACs and vitamin K antagonists 1, 2.
Imaging Requirements
- Always obtain brain imaging (CT or MRI) before initiating anticoagulation to exclude hemorrhage 1, 2
- Repeat imaging is essential for moderate-to-severe strokes to detect hemorrhagic transformation before starting DOACs 1, 2
- Patients with early signs of hemorrhage on neuroimaging are at highest risk and should delay oral anticoagulation to allow healing of the blood-brain barrier 1
Large Infarct Considerations
Patients with larger cerebral infarcts are at greater risk for hemorrhagic transformation and worse bleeding with early anticoagulation 1. Large infarcts are typically defined as NIHSS score >15 or lesions involving complete arterial territory or >1 arterial territory 1. It is reasonable to delay initiation of oral anticoagulation for 14 days after stroke onset in patients with large cerebral infarction 1.
DOAC Preference Over Other Anticoagulants
DOACs are strongly preferred over vitamin K antagonists (warfarin) or aspirin for secondary stroke prevention in atrial fibrillation patients 1, 2. DOACs reduce intracranial hemorrhage risk by approximately 51-56% compared to warfarin 1, 2. All four major DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) demonstrated advantages in stroke risk reduction with similar or improved bleeding profiles compared to warfarin 1.
What NOT to Do
- Do not use heparin or LMWH bridging therapy when initiating DOACs, as bridging is not recommended due to the rapid onset of action of DOACs and associated bleeding risk 1, 2, 3
- Do not use immediate parenteral anticoagulation (heparin, LMWH, heparinoids) in the acute phase, as this increases symptomatic intracranial bleeding (OR 2.89; 95% CI 1.19-7.01) without net benefit 1
- Do not combine oral anticoagulation with antiplatelet therapy after TIA or stroke, as combination therapy is not recommended 1
Special Circumstances
If Patient Was Already on a DOAC When Stroke Occurred
Continue the same DOAC rather than switching 4, 5. Switching to warfarin is associated with increased risk of recurrent ischemic stroke (aHR 1.96,95% CI 1.27-3.02) 4, and switching to a different DOAC is also associated with increased recurrence risk (aHR 1.62,95% CI 1.25-2.11) 4. Patients who remained on their initial DOAC had lower risks of ischemic stroke (RR 0.55), intracranial hemorrhage (RR 0.37), and hemorrhagic events (RR 0.44) compared to those switched to warfarin 5.
First assess and optimize adherence to therapy 1, 2. For moderate-to-severe strokes in patients already anticoagulated, interrupt anticoagulation for 3-12 days based on multidisciplinary assessment of acute stroke and bleeding risk 1.
Recent Evidence on Early Initiation
The 2024 OPTIMAS study found that early DOAC initiation (≤4 days from symptom onset) was not inferior to late initiation (7-14 days) for the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, or systemic embolism 2. However, the guideline-based approach of timing according to stroke severity remains the standard recommendation 1, 2.
Common Pitfalls to Avoid
- Do not delay beyond 14 days without clear contraindication, as the risk of recurrent ischemic stroke is 0.5-1.3% per day in the first 14 days 1
- Do not skip repeat imaging in moderate-to-severe strokes, as hemorrhagic transformation may not be apparent on initial imaging 1
- Do not use aspirin as a substitute for anticoagulation beyond the brief period until DOAC initiation 1
- Do not assume all strokes are the same—TIA patients can start immediately (day 1), while severe strokes require the full 12-14 day delay 1, 2