What is the evidence for adding antiplatelet agents to patients with transient ischemic attack (TIA) symptoms who are already on anticoagulants such as apixaban (Eliquis)?

From the Guidelines

The evidence does not support adding antiplatelet therapy to anticoagulation for patients who have experienced TIA symptoms while on anticoagulation, such as apixaban (Eliquis), due to increased bleeding risk without clear additional benefit for stroke prevention. This recommendation is based on the most recent and highest quality study, the 2024 ESC guidelines for the management of atrial fibrillation 1, which states that antiplatelet drugs, such as aspirin and clopidogrel, are not an alternative to oral anticoagulants (OAC) and should not be used for stroke prevention, as they can lead to potential harm.

The AVERROES trial, referenced in the 2024 ESC guidelines, demonstrated a lower rate of stroke or systemic embolism with apixaban compared with aspirin, with no significant difference in major bleeding 1. Additionally, the guidelines highlight that combining antiplatelet drugs with anticoagulants (DOACs or VKAs) should only occur in selected patients with acute vascular disease, and that bleeding events are more common when antithrombotic agents are combined, with no clear benefit observed in terms of prevention of stroke or death.

Key points to consider:

• The combination of antiplatelet therapy and anticoagulation increases bleeding risk without providing clear additional benefit for stroke prevention.
• If a patient experiences a TIA while appropriately anticoagulated, the recommended approach is to first ensure adequate anticoagulation and then consider alternative causes for symptoms or evaluate for a different stroke mechanism.
• For patients with atrial fibrillation who experience a TIA despite proper anticoagulation, optimizing other vascular risk factors is more appropriate than adding an antiplatelet.
• In rare cases where dual therapy is considered, such as in patients with concurrent coronary artery disease, this should be limited to the shortest duration possible and managed by specialists due to the substantially increased bleeding risk, as noted in the 2018 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation 1.

Overall, the evidence supports a cautious approach to adding antiplatelet therapy to anticoagulation, prioritizing the management of bleeding risk and optimizing other vascular risk factors to minimize morbidity, mortality, and improve quality of life.

From the Research

Evidence for Adding Antiplatelet Agents to Patients with TIA Symptoms on Anticoagulants

• The current evidence does not directly support the addition of antiplatelet agents to patients with transient ischemic attack (TIA) symptoms who are already on anticoagulants such as apixaban (Eliquis) 2, 3, 4, 5, 6.
• Studies have shown that dual antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor is effective in preventing recurrent stroke in patients with minor acute non-cardioembolic stroke or high-risk TIA, but the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy 2, 3, 4.
• The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance 2.
• Oral anticoagulants such as apixaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes, and may be preferred over warfarin due to decreased bleeding risks, including intracranial hemorrhage (ICH), lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions 2.
• There is limited evidence on the use of combination antiplatelet and oral anticoagulant therapy in patients with TIA, and further studies are needed to clarify the optimal antithrombotic therapy in this population 5, 6.

Key Considerations

• The risk of bleeding is a significant concern when adding antiplatelet agents to patients on anticoagulants, and physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen 2, 3, 4, 5, 6.
• The optimal duration of DAPT in symptomatic intracranial atherosclerosis is unclear, and further studies are warranted to study the benefit and risk of extended DAPT in this population 2.
• Emerging antiplatelets such as ticagrelor and cilostazol may work better in certain subgroups of stroke patients, which warrants further investigation 3, 4.