Should Aspirin (ASA) 81 milligrams daily be discontinued and Clopidogrel be initiated in a patient with multiple episodes suspicious for Transient Ischemic Attack (TIA)?

From the Guidelines

Aspirin (ASA) 81 milligrams daily should not be discontinued, and instead, dual antiplatelet therapy with both aspirin 81 mg daily and clopidogrel 75 mg daily should be considered for a limited period, typically 21-90 days, following TIA episodes, as this approach provides superior protection against recurrent stroke compared to either agent alone during the high-risk period following a TIA. When deciding on antiplatelet therapy for patients with a history of transient ischemic attack (TIA), it's crucial to consider the most recent and highest quality evidence available. According to the guidelines for the prevention of stroke in patients with stroke or transient ischemic attack from the American Heart Association/American Stroke Association 1, aspirin monotherapy, the combination of aspirin and extended-release dipyridamole, and clopidogrel monotherapy are all acceptable options for initial therapy. However, the selection of an antiplatelet agent should be individualized based on patient risk factor profiles, cost, tolerance, and other clinical characteristics. Key considerations include:

• The use of antiplatelet agents rather than oral anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events in patients with noncardioembolic ischemic stroke or TIA 1.
• The addition of aspirin to clopidogrel increases the risk of hemorrhage and is not recommended for routine secondary prevention after ischemic stroke or TIA, suggesting that dual therapy should be used judiciously and for limited durations 1.
• For patients who have an ischemic stroke while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit, supporting the consideration of alternative or additional antiplatelet agents like clopidogrel 1. Given these considerations, initiating clopidogrel in addition to aspirin for a patient with multiple episodes suspicious for TIA could be beneficial for a short period, but it's essential to weigh the benefits against the increased risk of bleeding complications and to closely monitor the patient. The initial clopidogrel dose should be a loading dose, followed by a daily maintenance dose, and the dual therapy should be transitioned to a single antiplatelet agent after the initial high-risk period, depending on the patient's response and risk factors.

From the FDA Drug Label

The CAPRIE trial was a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing clopidogrel (75 mg daily) to aspirin (325 mg daily) The trial’s primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. As shown in Table 6, clopidogrel was associated with a lower incidence of outcome events, primarily MI. The overall relative risk reduction (9. 8% vs 10.6%) was 8.7%, p=0.045.

The patient in question has had multiple episodes suspicious for Transient Ischemic Attack (TIA).

• The CAPRIE trial results suggest that clopidogrel may be more effective than aspirin in reducing the risk of ischemic events, particularly in patients with peripheral arterial disease.
• However, the benefit of clopidogrel over aspirin was less apparent in stroke patients.
• There is no direct information in the provided drug label that specifically addresses the scenario of a patient with multiple episodes suspicious for TIA.
• Given the lack of direct evidence, a conservative clinical decision would be to not discontinue Aspirin (ASA) 81 milligrams daily and initiate Clopidogrel without further evaluation and consideration of individual patient factors 2.

From the Research

Antiplatelet Therapy for Transient Ischemic Attack (TIA)

• The decision to discontinue Aspirin (ASA) 81 milligrams daily and initiate Clopidogrel in a patient with multiple episodes suspicious for Transient Ischemic Attack (TIA) should be based on the patient's individual risk factors and medical history 3, 4, 5, 6.
• Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA 3, 5.
• Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA 3, 5.
• A meta-analysis found that DAPT with clopidogrel and aspirin significantly reduced the risk of stroke compared to aspirin monotherapy in patients with mild-to-moderate stroke and TIA, with no significant difference in all bleeding events and moderate to severe bleeding events 6.

Considerations for Discontinuing Aspirin and Initiating Clopidogrel

• 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 3, 4, 7.
• Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen 3, 4, 5.
• Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis and to elucidate optimal strategies for balancing stroke prevention with bleeding risk mitigation in patients with TIA or ischemic stroke 3, 4, 5, 6.