What are the indications for anticoagulant therapy in patients with ischemic stroke?

Indications for Anticoagulant Therapy in Ischemic Stroke

Anticoagulation is indicated for secondary stroke prevention in patients with ischemic stroke or TIA and atrial fibrillation (including paroxysmal AF), with direct oral anticoagulants (DOACs) preferred over warfarin, typically initiated within 2 weeks of stroke onset depending on hemorrhagic transformation risk. 1

Primary Indication: Atrial Fibrillation

For patients with ischemic stroke or TIA and atrial fibrillation, oral anticoagulation is strongly recommended as secondary prevention. 1 This represents the most robust indication for anticoagulation in stroke patients, supported by high-quality evidence demonstrating significant reduction in recurrent stroke risk. 2

Choice of Anticoagulant

• DOACs (apixaban, dabigatran, edoxaban, or rivaroxaban) are preferred over warfarin for nonvalvular atrial fibrillation due to lower risk of major bleeding, intracranial hemorrhage, and death. 3, 4, 2
• Dabigatran 150 mg twice daily is specifically suggested over adjusted-dose warfarin (INR 2.0-3.0) in this population. 1
• Recent evidence confirms DOACs have better prognosis than warfarin after ischemic stroke, with apixaban and edoxaban showing particularly reduced mortality risk. 5

Timing of Anticoagulation Initiation

The timing algorithm depends on hemorrhagic transformation risk:

Low-risk patients (small infarct burden, no hemorrhage on imaging):

• Initiate anticoagulation within 1-2 weeks after stroke onset 1
• Can consider earlier initiation (within 4 days) in very low-risk cases 3
• For TIA patients, start immediately to reduce recurrent stroke risk 3

Standard-risk patients:

• Initiate oral anticoagulation within 2 weeks of acute ischemic stroke 1
• Bridge with aspirin until anticoagulation reaches therapeutic level 1

High-risk patients (extensive infarct burden, hemorrhagic transformation on imaging):

• Delay anticoagulation beyond 2 weeks 1
• For higher-grade hemorrhagic transformation (HI2, PH1, PH2), wait 7-10 days minimum 6
• Confirm absence of hemorrhage progression on repeat imaging before initiating 3

Critical timing caveat: Very early anticoagulation (<48 hours) using heparinoids or warfarin should NOT be used, as it increases symptomatic intracranial hemorrhage risk without net benefit. 1

Secondary Indications

Mechanical Heart Valves and Valvular Disease

• Warfarin (INR 2.5-3.5) plus aspirin 75-100 mg daily is indicated for mechanical mitral valve. 3
• Warfarin remains the anticoagulant of choice for moderate to severe mitral stenosis. 3
• DOACs are contraindicated in these populations. 3

Left Ventricular or Atrial Thrombus

• Anticoagulation for at least 3 months is recommended when thrombus is identified. 3
• Vitamin K antagonists are preferred for left atrial/appendage thrombus with cardiomyopathy. 3

Cerebral Venous Sinus Thrombosis

• Anticoagulation is suggested over no anticoagulant therapy during both acute and chronic phases (Grade 2C recommendation). 1
• Continue for at least 3 months followed by antiplatelet therapy. 1

Arterial Dissection

• Antithrombotic treatment for at least 3-6 months is reasonable for patients with extracranial carotid or vertebral arterial dissection. 1
• The relative efficacy of antiplatelet therapy versus anticoagulation remains unknown in this population. 1

Inherited Thrombophilias with Venous Thrombosis

• Patients with arterial ischemic stroke and established inherited thrombophilia should be evaluated for DVT, which indicates short- or long-term anticoagulation. 1
• For spontaneous cerebral venous thrombosis with inherited thrombophilia, long-term anticoagulation is probably indicated. 1

Antiphospholipid Antibody Syndrome

• For patients meeting criteria for antiphospholipid antibody syndrome, oral anticoagulation with target INR 2.0-3.0 is reasonable. 1

Special Populations Requiring Modified Approach

End-Stage Renal Disease or Dialysis

• Warfarin or dose-adjusted apixaban may be reasonable options. 3
• Dabigatran is contraindicated with creatinine clearance ≤30 mL/min. 1

Pregnancy

• Adjusted-dose unfractionated heparin throughout pregnancy may be considered for high-risk thromboembolic conditions. 1

Prior Intracerebral Hemorrhage

• After spontaneous ICH, anticoagulation should be delayed beyond 48 hours and probably for at least 4 weeks. 7
• Consider anticoagulation with NOACs after careful risk-benefit assessment in high ischemic stroke risk patients. 1
• Deep ICH locations have more favorable benefit-risk profiles than lobar hemorrhages. 7
• For probable cerebral amyloid angiopathy, consider left atrial appendage occlusion instead. 1, 7

What NOT to Anticoagulate

Anticoagulation is NOT indicated for:

• Non-cardioembolic ischemic stroke (use antiplatelet therapy instead) 4
• Primary intracerebral hemorrhage for long-term stroke prevention (Grade 2C against) 1
• Acute ischemic stroke in general population without specific indications (aspirin 160-325 mg is preferred) 1
• Bridging with heparinoids in acute phase (<48 hours) of stroke due to increased hemorrhage risk 1

Common Pitfalls to Avoid

• Do not use subcutaneous unfractionated heparin for reducing early stroke recurrence—benefit is offset by increased hemorrhage risk. 1
• Do not use dose-adjusted IV unfractionated heparin or high-dose LMWH/heparinoids in acute stroke—not efficacious and may increase bleeding. 1
• Do not assume cardioembolic stroke mechanism alone justifies immediate anticoagulation—early recurrence risk is actually low, and bleeding risk may outweigh benefit. 1
• Do not restart anticoagulation immediately after hemorrhagic transformation—wait 7-10 days for higher-grade bleeds. 6