Should clopidogrel be initiated in a patient with a recent episode suspicious for Transient Ischemic Attack (TIA) while on Aspirin (Acetylsalicylic Acid, ASA) 81 milligrams daily?

From the Guidelines

Clopidogrel should not be initiated in a patient with a recent episode suspicious for Transient Ischemic Attack (TIA) while on Aspirin (Acetylsalicylic Acid, ASA) 81 milligrams daily, as the combination of clopidogrel and aspirin has been shown to significantly increase the risk of major hemorrhage without providing a significant benefit in reducing vascular events, as demonstrated in the MATCH trial 1.

The use of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin in patients with TIA or ischemic stroke has been evaluated in several studies. However, the most recent and highest quality study, the CHANCE trial, which was published in 2013 but mentioned in the 2016 European guidelines 1, showed that the combined treatment of clopidogrel and aspirin decreased the 90-day risk of stroke without increasing hemorrhage compared to aspirin alone in Chinese patients with minor stroke or TIA.

However, considering the overall evidence, including the MATCH trial 1 and the European guidelines 1, the risk of bleeding complications associated with DAPT should not be overlooked. The European guidelines 1 also mention that adding aspirin to clopidogrel in high-risk patients with recent ischemic stroke or TIA was associated with a non-significant difference in reducing major vascular events, but the risk of life-threatening or major bleeding was significantly increased.

Key points to consider in the management of patients with TIA include:

• Monitoring for bleeding complications during DAPT
• Ensuring the patient undergoes a complete workup to confirm the TIA diagnosis and identify underlying causes
• Providing comprehensive vascular risk factor management, including blood pressure control, lipid management, and lifestyle modifications
• Weighing the benefits and risks of DAPT in individual patients, considering factors such as the severity of the TIA, the presence of other vascular risk factors, and the patient's overall health status.

In clinical practice, the decision to initiate clopidogrel in a patient with a recent TIA while on aspirin should be made on a case-by-case basis, taking into account the individual patient's risk factors and the potential benefits and risks of DAPT, as well as the results of the most recent and highest quality studies, such as the CHANCE trial mentioned in 1.

From the FDA Drug Label

1.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease In patients with established peripheral arterial disease or with a history of recent myocardial infarction (MI) or recent stroke clopidogrel tablets are indicated to reduce the rate of MI and stroke.

Initiation of Clopidogrel in a Patient with Recent TIA on Aspirin:

• The FDA drug label indicates that clopidogrel is used to reduce the rate of myocardial infarction and stroke in patients with a history of recent stroke 2.
• Since a Transient Ischemic Attack (TIA) is often considered a precursor to a full stroke and shares similar pathophysiology, it can be reasoned that the benefits of clopidogrel in stroke prevention might extend to patients with a recent episode suspicious for TIA.
• The label specifies that clopidogrel should be administered in conjunction with aspirin for patients with acute coronary syndrome, and by extension, this dual antiplatelet therapy could be beneficial for patients with a recent TIA.
• Key Consideration: The patient is already on Aspirin (Acetylsalicylic Acid, ASA) 81 milligrams daily, which is a common regimen for patients at risk of cardiovascular events.
• Clinical Decision: Given the information from the drug label and considering the patient's current aspirin regimen, clopidogrel could be initiated in a patient with a recent episode suspicious for TIA, as it may provide additional protection against future ischemic events when used in conjunction with aspirin 2, 2.

From the Research

Dual Antiplatelet Therapy for TIA and Minor Stroke

• Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA) 3.
• The combination of clopidogrel and aspirin has been shown to be superior to aspirin alone in the prevention of recurrent stroke and death 3, 4.
• However, the optimal duration of DAPT is still unclear, with some studies suggesting that short-term DAPT (≤3 months) may be sufficient, while others recommend prolonged DAPT (≥1 year) 4, 5.

Comparison of Clopidogrel and Ticagrelor

• Ticagrelor has been shown to be superior to clopidogrel in inhibiting platelet reactivity in patients with minor stroke or TIA 6.
• However, there is no statistically significant difference between clopidogrel and ticagrelor in the prevention of recurrent stroke and death 3.

Clinical Practice and Guidelines

• National guidelines recommend treatment with aspirin plus clopidogrel, DAPT, within 24 hours of high-risk TIA or minor stroke symptoms to eligible patients 7.
• However, a survey of emergency medicine physicians found that the reported rate of DAPT treatment for eligible patients with high-risk TIA and minor stroke was low, with many physicians opting for aspirin alone or deferring medical management to consultants or another team 7.

Initiation of Clopidogrel in Patients with Recent TIA

• Based on the available evidence, it is reasonable to initiate clopidogrel in a patient with a recent episode suspicious for TIA while on aspirin (Acetylsalicylic Acid, ASA) 81 milligrams daily, as part of a DAPT regimen 3, 4, 5.
• However, the decision to initiate clopidogrel should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history.