Anticoagulant and Antithrombotic Management for Chronic Stroke
Primary Recommendation
For patients with chronic stroke and atrial fibrillation, direct oral anticoagulants (DOACs)—specifically apixaban, dabigatran, edoxaban, or rivaroxaban—are strongly recommended over warfarin to reduce recurrent stroke risk, regardless of whether AF is paroxysmal, persistent, or permanent. 1
Anticoagulation Strategy for Atrial Fibrillation with Chronic Stroke
DOAC Selection and Dosing
DOACs are preferred over warfarin because they demonstrate superior or non-inferior efficacy in preventing recurrent stroke while significantly reducing major bleeding risk, including intracranial hemorrhage 1
Apixaban is particularly advantageous as it has the lowest renal elimination (25%) among DOACs, making it safer in renal impairment 2, 3
Dabigatran dosing for AF with CrCl >30 mL/min: 150 mg twice daily; for CrCl 15-30 mL/min: 75 mg twice daily 4
For patients with CrCl 30-50 mL/min taking dabigatran, reduce dose to 75 mg twice daily if concomitantly using P-gp inhibitors (dronedarone or systemic ketoconazole) 4
Renal Function Considerations
Apixaban or warfarin are the only options for patients with end-stage renal disease or on dialysis, with dose adjustment as indicated 1
Avoid dabigatran in patients with CrCl <30 mL/min or on dialysis, as dosing recommendations cannot be provided for this population 4
Rivaroxaban carries higher bleeding risk in severe renal impairment due to significant renal excretion (66%), compared to apixaban's 25% 2, 3
Monitor renal function regularly and adjust therapy accordingly, particularly in situations that may cause renal function decline 4
Timing of Anticoagulation Initiation After Stroke
For TIA with AF: Initiate anticoagulation immediately after the index event 1
For stroke at low hemorrhagic conversion risk: Initiate anticoagulation 2-14 days after the event 1
For stroke at high hemorrhagic conversion risk: Delay anticoagulation beyond 14 days to reduce intracranial hemorrhage risk 1
For large strokes with extensive infarct or hemorrhagic transformation: Delay anticoagulation beyond 2 weeks 5
Management for Chronic Stroke WITHOUT Atrial Fibrillation
Single Antiplatelet Therapy
Clopidogrel 75 mg once daily is preferred over aspirin for long-term secondary prevention in noncardioembolic stroke 6
Aspirin 75-100 mg daily is an acceptable alternative if clopidogrel is contraindicated 7
Aspirin/extended-release dipyridamole combination is preferred over aspirin monotherapy for long-term prevention 7
Critical Safety Considerations
Contraindications and Monitoring
Exclude intracranial hemorrhage on neuroimaging before initiating any antithrombotic therapy 7
Assess blood pressure control: Target systolic <185 mmHg and diastolic <110 mmHg before anticoagulation 6
Do not increase anticoagulation intensity or add antiplatelet agents in patients who experience stroke while on therapeutic anticoagulation, as this increases bleeding without reducing ischemic events 5
Use aPTT or ECT (not INR) to assess anticoagulant activity in patients on dabigatran 4
Warfarin Management (When DOACs Contraindicated)
Target INR 2.0-3.0 for patients with AF and prior stroke or TIA 1
Monitor INR weekly during initiation and monthly when stable 1
Warfarin is associated with progressive GFR decline compared to DOACs, making it less favorable in chronic kidney disease 8
Venous Thromboembolism Prophylaxis
Prophylactic-dose low-molecular-weight heparin is preferred over unfractionated heparin for immobilized stroke patients 6, 5
Intermittent pneumatic compression devices are an alternative for VTE prophylaxis 6, 5
Avoid elastic compression stockings as they are not beneficial 6
Common Pitfalls to Avoid
Do not use aspirin alone for stroke prevention in AF patients, as it is significantly less effective than anticoagulation (20-30% risk reduction vs. 68% with warfarin) 9
Do not combine different DOAC dosage forms on a milligram-to-milligram basis, as bioavailability differs 4
Do not use dabigatran with P-gp inhibitors in patients with CrCl <30 mL/min 4
Do not substitute antiplatelet therapy for anticoagulation in AF patients with prior stroke, as aspirin has not been shown to significantly reduce recurrent stroke risk in secondary prevention 9