What anticoagulants are recommended after an ischemic stroke?

Anticoagulant Recommendations After Ischemic Stroke

Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists (warfarin) for secondary stroke prevention in patients with non-valvular atrial fibrillation after an ischemic stroke. 1

Anticoagulation Based on Stroke Etiology

Atrial Fibrillation

• For patients with ischemic stroke or TIA with non-valvular atrial fibrillation (paroxysmal, persistent, or permanent), oral anticoagulation is strongly recommended 1
• DOACs are preferred over vitamin K antagonists in non-valvular atrial fibrillation due to better outcomes and lower bleeding risk 1, 2
• For patients unable to take oral anticoagulants, aspirin 325 mg/day is recommended, though less effective than anticoagulation 1
• For patients receiving vitamin K antagonists who cannot achieve consistent INR levels, switching to a DOAC is preferred 1
• Recent evidence shows that patients who experience stroke while on DOACs have lower mortality rates than those on warfarin (adjusted HR 0.596,95% CI 0.536-0.663) 2

Valvular Heart Disease

• For patients with valvular atrial fibrillation (mechanical valve replacement or moderate/severe mitral stenosis), oral anticoagulation with warfarin is recommended 1
• For patients with mechanical prosthetic heart valves, oral anticoagulants with an INR target of 3.0 (range 2.5-3.5) are recommended 1
• For patients with mechanical mitral valves and previous stroke/TIA, adding aspirin 75-100 mg daily to warfarin (target INR 2.5-3.5) is recommended 1
• For patients with bioprosthetic heart valves without other thromboembolism sources, antiplatelet therapy is recommended beyond 3-6 months post-procedure 1

Left Ventricular Thrombus

• For patients with ischemic stroke and left ventricular thrombus, anticoagulation for at least 3 months is recommended 1
• For patients with stroke caused by acute MI with LV mural thrombus, oral anticoagulation with INR 2.0-3.0 for 3 months to 1 year is reasonable 1
• Aspirin should be used concurrently for ischemic CAD patients during oral anticoagulant therapy (doses up to 162 mg/day, preferably enteric-coated) 1

Cardiomyopathy

• For patients with stroke/TIA and left atrial/left atrial appendage thrombus in the context of cardiomyopathy and LV dysfunction, oral anticoagulation with vitamin K antagonists is recommended for at least 3 months 1
• For patients with dilated cardiomyopathy, either warfarin (INR 2.0-3.0) or antiplatelet therapy may be considered 1

Timing of Anticoagulation After Stroke

• Parenteral anticoagulation within 48 hours of acute ischemic stroke is associated with increased risk of hemorrhagic transformation and is not recommended 3
• The optimal timing for initiating oral anticoagulation after stroke depends on infarct size and presence of hemorrhage 3
• DOAC initiation within 2 days of acute ischemic stroke is associated with a 5% rate of hemorrhagic transformation 3

Special Considerations

Cerebral Venous Sinus Thrombosis

• For patients with cerebral venous sinus thrombosis, unfractionated heparin or low molecular weight heparin is reasonable even with hemorrhagic infarction 1
• Continuation of anticoagulation with an oral anticoagulant for 3-6 months, followed by antiplatelet therapy is reasonable 1

Antithrombotic Management After Cerebral Hemorrhage

• For patients who develop intracranial hemorrhage, subarachnoid hemorrhage, or subdural hematoma, all anticoagulants and antiplatelets should be discontinued during the acute period (at least 1-2 weeks) 1
• Anticoagulant effects should be reversed immediately with appropriate agents (vitamin K, fresh frozen plasma) 1
• Oral anticoagulants may be resumed after 3-4 weeks with rigorous monitoring and maintenance of INRs in the lower end of the therapeutic range 1

Important Caveats

• Patients suitable for anticoagulation should not receive antiplatelets for secondary stroke prevention 1
• Switching from one DOAC to another or from DOAC to warfarin after a stroke while on a DOAC is associated with increased risk of recurrent ischemic stroke (aHR 1.62,95% CI 1.25-2.11 for DOAC switch; aHR 1.96,95% CI 1.27-3.02 for warfarin switch) 4
• Adding antiplatelet therapy to anticoagulation increases bleeding risk without reducing ischemic events in most cases 1, 4
• Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein modulators, and large artery atherosclerotic disease are predictors of recurrent ischemic stroke despite anticoagulation 4