What is the initial management approach for a patient with new onset stroke and atrial fibrillation, should it be antiplatelet therapy, anticoagulant therapy, or thrombolysis with tissue Plasminogen Activator (tPA)?

Management of New Onset Stroke with Atrial Fibrillation

For patients with acute ischemic stroke and atrial fibrillation presenting within 4.5 hours of symptom onset who are not on therapeutic anticoagulation, administer intravenous thrombolysis with rtPA (0.9 mg/kg, maximum 90 mg) immediately, followed by delayed initiation of oral anticoagulation based on stroke severity (1-12 days post-stroke). 1, 2

Acute Phase Management: Thrombolysis Decision

Eligibility for rtPA

• Administer rtPA within 3 hours of symptom onset (strong recommendation) if no contraindications exist, as this provides the greatest absolute benefit 3
• Between 3-4.5 hours, rtPA administration is conditionally recommended, with benefits still outweighing risks 2, 3
• Beyond 4.5 hours, do not administer rtPA as it is contraindicated 3

Critical Contraindications to Thrombolysis

• Patients on therapeutic oral anticoagulation should NOT receive rtPA 1
• rtPA can be given if INR <1.7 in patients on warfarin 1
• For dabigatran-treated patients, rtPA may be considered only if aPTT is normal and last dose was >48 hours prior 1
• For patients on DOACs like apixaban or rivaroxaban, do NOT routinely administer rtPA due to substantially elevated bleeding risk 4

rtPA Dosing Protocol

• Total dose: 0.9 mg/kg (maximum 90 mg) 2, 5
• 10% given as IV bolus over 1 minute 2, 5
• Remaining 90% infused over 60 minutes 2, 5

Alternative: Mechanical Thrombectomy

• Thrombectomy can be performed in anticoagulated patients with large vessel occlusion (internal carotid or middle cerebral artery) within 6 hours 1
• This option remains viable even when thrombolysis is contraindicated 1, 4

Post-Acute Phase: Anticoagulation Initiation

Timing Based on Stroke Severity

The 2016 ESC Guidelines provide a consensus-based algorithm for anticoagulation initiation: 1

First: Exclude Intracranial Hemorrhage

• Obtain CT or MRI immediately to exclude hemorrhagic transformation 1

Second: Stratify by NIHSS Score

For TIA patients:

• Start oral anticoagulation 1 day after the acute event 1

For mild stroke (NIHSS <8):

• Repeat brain imaging at day 6 to evaluate for hemorrhagic transformation 1
• If no hemorrhage, start oral anticoagulation at day 6 1

For moderate stroke (NIHSS 8-15):

• Repeat brain imaging at day 6 1
• If no hemorrhage, start oral anticoagulation at day 6 1

For severe stroke (NIHSS ≥16):

• Repeat brain imaging at day 12 to assess hemorrhagic transformation 1
• If no hemorrhage, start oral anticoagulation at day 12 1

Rationale for Delayed Anticoagulation

• Parenteral anticoagulation in the first 7-14 days increases symptomatic intracranial bleeding risk (OR 2.89; 95% CI 1.19-7.01) without significant reduction in recurrent ischemic stroke 1
• The bleeding risk from early anticoagulation exceeds stroke prevention benefit in large strokes 1
• Patients with TIA or small stroke may benefit from immediate anticoagulation initiation 1

Choice of Long-Term Anticoagulant

Preferred Agents

• NOACs (direct oral anticoagulants) are preferred over warfarin for long-term secondary stroke prevention in atrial fibrillation 1
• NOACs demonstrate fewer intracranial hemorrhages and hemorrhagic strokes (OR 0.44; 95% CI 0.32-0.62) compared to warfarin 1

Warfarin Alternative

• If warfarin is used, target INR 2.5 (range 2.0-3.0) 6, 3
• Warfarin requires meticulous INR monitoring 6

Antiplatelet Therapy Considerations

If Thrombolysis is NOT Given

• Initiate aspirin 160-325 mg within 24-48 hours after excluding intracranial hemorrhage in patients not receiving anticoagulation 2, 3
• Early aspirin therapy improves outcomes in acute ischemic stroke patients who do not receive thrombolysis 3

Important Caveat

• Do NOT use antiplatelet therapy as a substitute for anticoagulation in atrial fibrillation patients at moderate-to-high stroke risk 1
• Anticoagulation reduces stroke risk by approximately 64% in atrial fibrillation, far superior to antiplatelet therapy alone 7

Critical Pitfalls to Avoid

• Never delay thrombolysis to obtain anticoagulation history if patient meets clinical criteria and has no known contraindications 5
• Do not use standard coagulation tests (PT/INR, aPTT) to guide decisions about DOAC levels for thrombolysis eligibility 4
• Do not start anticoagulation too early after large strokes without repeat imaging to assess hemorrhagic transformation risk 1
• If a patient suffers stroke while on anticoagulation, consider switching to a different anticoagulant 1

Special Considerations

Patients Already on Anticoagulation

• Systemic thrombolysis is contraindicated in patients on therapeutic anticoagulation 1
• Consider mechanical thrombectomy as the primary reperfusion strategy 1, 4
• With idarucizumab (dabigatran reversal agent) available, thrombolysis may be feasible after reversal in selected cases 1

Monitoring After rtPA

• Symptomatic intracranial hemorrhage occurs in 6.4% of rtPA-treated patients versus 0.6% of placebo patients 2
• In atrial fibrillation patients specifically, rtPA increases intracranial hemorrhage risk (18.2% vs 6.8%) but significantly improves functional outcomes (36.4% vs 13.6% with favorable 90-day mRS 0-1) 8