When can anticoagulation be started in a patient with atrial fibrillation (AF) and a recent middle cerebral artery (MCA) infarct?

Timing of Anticoagulation After Acute MCA Infarct in Atrial Fibrillation

Anticoagulation should be started within 2 weeks of the acute ischemic stroke, but avoid initiating therapy within the first 48 hours. 1

Critical Early Period (First 48 Hours)

• Do not start anticoagulation with heparinoids or warfarin within 48 hours of stroke onset 1
• Heparinoids increase the risk of symptomatic intracranial hemorrhage without providing net benefit when used as bridging therapy in the acute phase 1
• Very early anticoagulation (<48 hours) should be avoided regardless of the anticoagulant type 1

Optimal Timing Window (Days 1-14)

• Oral anticoagulation should usually be started within 2 weeks of acute ischemic stroke 1
• The exact optimal timing within this 2-week period remains uncertain, but observational data suggest starting between days 4-7 may be reasonable 1
• One observational study showed improved outcomes with NOACs started at a median of 4 days post-stroke without early intracranial hemorrhage 1
• A small randomized trial (Triple AXEL) found similar rates of recurrent ischemia and intracranial bleeding when rivaroxaban was started within 5 days compared to warfarin 1

Factors Influencing Timing Decision

Infarct size considerations:

• While infarct size is commonly used clinically to guide timing, it predicts higher risk of both early recurrent ischemia AND hemorrhagic transformation 1
• This dual risk makes infarct size less helpful in determining net benefit of early treatment 1
• Larger infarcts may warrant waiting closer to 2 weeks, while smaller infarcts may allow earlier initiation around day 4-7 1

Anticoagulant Selection

Prefer direct oral anticoagulants (DOACs) over warfarin:

• DOACs show promise in observational studies when started within the first week post-stroke 1
• DOACs have not been formally tested in randomized trials for early post-stroke initiation (within 1 week), but observational data are encouraging 1
• Choose apixaban, dabigatran, rivaroxaban, or edoxaban over warfarin for non-valvular atrial fibrillation 2

Long-Term Management

• Long-term oral anticoagulation is strongly recommended as secondary prevention 1
• Continue anticoagulation indefinitely based on the patient's CHA₂DS₂-VASc score, not on whether sinus rhythm is restored 1, 2
• Target INR 2.0-3.0 if warfarin is used 1, 3

Common Pitfalls to Avoid

• Never use heparin or low-molecular-weight heparin as bridging therapy in acute stroke - this increases hemorrhagic transformation risk without benefit 1
• Do not delay anticoagulation beyond 2 weeks - the risk of recurrent cardioembolic stroke increases significantly 1
• Do not withhold long-term anticoagulation even if the patient appears to be in sinus rhythm - paroxysmal AF recurrence is common and often asymptomatic 1, 2

Practical Algorithm for This 60-Year-Old Patient

Day 1 (current status):

• Avoid all anticoagulation 1
• Assess infarct size on imaging
• Calculate CHA₂DS₂-VASc score (likely ≥2 given age and stroke) 2

Days 2-3:

• Continue to avoid anticoagulation 1
• Monitor for hemorrhagic transformation
• Ensure hemodynamic stability

Days 4-7:

• Consider initiating a DOAC if infarct is small-to-moderate size 1
• Start with standard dosing (e.g., apixaban 5mg twice daily, rivaroxaban 20mg daily, dabigatran 150mg twice daily) 2

Days 7-14:

• If not yet started, initiate anticoagulation by day 14 at the latest 1
• Even large infarcts should have anticoagulation started by 2 weeks 1

Beyond 2 weeks:

• Continue anticoagulation indefinitely for secondary stroke prevention 1