Should a patient with infective endocarditis who has an acute stroke receive antiplatelet therapy or systemic anticoagulation, and if so, what timing and dosing are recommended?

Antiplatelet and Anticoagulation in Infective Endocarditis-Related Stroke

Primary Recommendation

Discontinue all anticoagulation immediately at presentation of infective endocarditis with stroke, and do not initiate antiplatelet therapy as routine treatment. 1, 2

Initial Management Algorithm

Step 1: Immediate Anticoagulation Cessation

• Stop all forms of anticoagulation (warfarin, heparin, DOACs) at the time of IE diagnosis, regardless of mechanical valve status or atrial fibrillation indication 1, 2
• The rationale is preventing hemorrhagic transformation of embolic lesions and bleeding from septic arteritis or mycotic aneurysms 1
• This applies even to patients with mechanical prosthetic valves who typically require lifelong anticoagulation 1

Step 2: Urgent Neurological Imaging

• Obtain immediate brain CT or MRI to exclude intracranial hemorrhage or embolic stroke 1, 2, 3
• MRI with gadolinium offers superior sensitivity for detecting cerebral lesions and influences surgical timing 1, 3
• Consider CT or MRI angiography if intracranial hemorrhage is present to rule out infectious (mycotic) aneurysms 1

Step 3: Multidisciplinary Team Consultation

• Assemble an endocarditis team including cardiac surgery, cardiology, infectious disease, neurology, and interventional neuroradiology 1, 3
• Decisions about anticoagulation timing must involve this team, particularly neurology if cerebrovascular complications are present 1

Evidence Against Antithrombotic Therapy in IE

Anticoagulation Does Not Prevent Embolic Events

• Anticoagulant therapy does not reduce the risk of embolic stroke in IE and may increase the risk of catastrophic intracranial hemorrhage 1, 2, 4
• Embolic rates decrease rapidly after initiation of antibiotic therapy alone, with most events occurring in the first 2-4 weeks 1, 2, 4
• The benefit of anticoagulation for preventing emboli is not supported by evidence, while bleeding risk is substantially elevated 1, 4

Antiplatelet Therapy Is Not Recommended

• Do not initiate aspirin or other antiplatelet agents as adjunctive therapy in IE (Class III recommendation) 1
• There is no evidence that routine aspirin reduces embolic stroke risk in patients already receiving antibiotic therapy 1
• If patients were on long-term antiplatelet therapy before IE diagnosis with no bleeding complications, continuation may be considered (Class IIb), but initiation is not recommended 1, 5

Management of Specific Clinical Scenarios

Mechanical Valve IE with Stroke

• Discontinue anticoagulation for at least 2 weeks of antibiotic therapy to prevent hemorrhagic conversion (Class IIa recommendation) 1, 2
• This applies even though mechanical valves carry thrombotic risk, as hemorrhagic transformation risk outweighs thrombotic concerns 1, 6
• Hemorrhagic transformation occurred in 13.8% of prosthetic valve endocarditis cases in one series, even with subtherapeutic anticoagulation 6

Atrial Fibrillation with IE

• Stop warfarin at IE presentation until CNS involvement is excluded and patient stabilizes 2
• Resume warfarin (INR 2.0-3.0) only after: no CNS involvement on imaging, clinical stability achieved, no urgent surgery planned, and at least 2 weeks of antibiotics completed if any CNS event occurred 2
• Do not use DOACs in patients with prosthetic valves - they are contraindicated 2

Staphylococcus aureus IE

• Exercise particular caution with S. aureus prosthetic valve IE, which has the highest risk of CNS complications 2
• Anticoagulation should remain discontinued for at least 2 weeks in S. aureus IE with recent CNS events 2

Timing of Anticoagulation Resumption

When Anticoagulation Can Be Reconsidered

Resume anticoagulation only when ALL of the following criteria are met:

• At least 2 weeks of effective antibiotic therapy completed if any CNS embolic event occurred 1, 2
• No intracranial hemorrhage or mycotic aneurysm on imaging 1, 2
• Patient clinically stable without ongoing sepsis 2
• No urgent cardiac surgery planned 1, 2
• Separate indication exists (mechanical valve, atrial fibrillation) 1, 2

Bridging Therapy Considerations

• Avoid intravenous unfractionated heparin during acute IE - studies show increased risk of hemorrhagic stroke 1
• There is no evidence supporting bridging therapy with subcutaneous or intravenous anticoagulation while off warfarin 1
• The strength of evidence for bridging is low, and institutional practices vary 1

Critical Pitfalls to Avoid

Common Errors

• Do not continue anticoagulation "because of the mechanical valve" - hemorrhagic transformation risk supersedes thrombotic concerns in acute IE 1, 6
• Do not add aspirin routinely - it does not reduce embolic events and increases bleeding risk 1
• Do not use therapeutic enoxaparin - case reports document hemorrhagic stroke exacerbation with low molecular weight heparin 7
• Do not use fibrinolytic therapy for acute stroke in IE - associated with increased hemorrhagic transformation risk 8

Hemorrhagic Complications

• Intracerebral hemorrhage occurs in approximately 5% of IE patients and is the most severe complication 5
• Hemorrhagic transformation can occur even with subtherapeutic anticoagulation levels 6
• Anticoagulation-related bleeding carries high morbidity and mortality in the IE population 4, 5

Special Considerations

Subclinical Neurological Events

• Subclinical neurological abnormalities occur in 25% of IE patients with S. aureus and up to 55% of critically ill IE patients 1
• Consider cerebral MRI in patients with valvular indications for anticoagulation to evaluate for subclinical cerebrovascular complications before resuming anticoagulation 1
• This is particularly important before cardiac surgery to identify those at higher risk of intracranial bleeding with cardiopulmonary bypass and heparin 1

Surgical Timing

• Early surgery (during initial hospitalization) is required in approximately 50% of PVE cases 1
• Anticoagulation status affects surgical timing, and patients should undergo neurological evaluation before surgery even without symptoms if imaging shows cerebral embolism 2
• The benefit of surgery in preventing embolic events is greatest early in treatment when embolic rates are highest 1