Should a patient experiencing a second Transient Ischemic Attack (TIA) while on Aspirin (acetylsalicylic acid) be switched to Plavix (clopidogrel)?

From the Guidelines

For a patient who has a second transient ischemic attack (TIA) while on aspirin, switching to clopidogrel (Plavix) is generally recommended. The typical dosage for clopidogrel is 75 mg once daily, taken long-term for secondary stroke prevention. This switch is appropriate because having a recurrent cerebrovascular event while on aspirin suggests that the current antiplatelet therapy is not providing adequate protection. Clopidogrel works through a different mechanism than aspirin, inhibiting platelet aggregation by blocking the P2Y12 receptor rather than affecting thromboxane production.

Key Considerations

• According to the guidelines for the prevention of stroke in patients with stroke or transient ischemic attack 1, clopidogrel may be slightly more effective than aspirin in the prevention of further vascular events.
• The selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, and other clinical characteristics 1.
• For patients who have an ischemic stroke while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit 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 1.

Management Approach

• In some cases, your doctor might consider dual antiplatelet therapy with both aspirin and clopidogrel for a short period (typically 21-90 days) following the recurrent TIA, before transitioning to clopidogrel monotherapy for long-term management.
• This approach provides more intensive antiplatelet coverage during the highest risk period for recurrence.
• It's essential to take clopidogrel at the same time each day and continue it indefinitely unless directed otherwise by your healthcare provider.

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 had a 2nd TIA while on aspirin. The CAPRIE trial compared clopidogrel to aspirin in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease. The results showed that clopidogrel was associated with a lower incidence of outcome events, primarily MI. However, the benefit of clopidogrel over aspirin was heterogeneous across subgroups, and the difference may be a chance occurrence.

• In patients with recent stroke, the benefit of clopidogrel over aspirin was less apparent.
• The study does not provide clear evidence to support switching to Plavix (clopidogrel) in a patient who had a 2nd TIA while on aspirin 2. Therefore, based on the available data, it is unclear whether to switch to Plavix (clopidogrel) in this scenario.

From the Research

Management of TIA on Aspirin

• The management of patients who experience a second transient ischemic attack (TIA) while on aspirin therapy is a complex issue, with various treatment options available 3, 4.
• According to the study by 3, alternative antiplatelet therapy for stroke prevention is indicated for patients who experience TIAs while on aspirin therapy.
• The combination of aspirin and extended-release dipyridamole reduces the risk of stroke following a TIA, and thieno-pyridines (e.g., clopidogrel and ticlopidine) are an alternative for patients at high risk for a cardioembolic event 4.

Dual Antiplatelet Therapy

• Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been shown to be effective in reducing the risk of recurrent stroke in patients with high-risk TIA or minor ischemic stroke, but it increases the risk of major bleeding events 5, 6.
• A meta-analysis of randomized controlled trials found that DAPT with aspirin and a P2Y12 inhibitor (e.g., clopidogrel) for up to 3 months reduces the risk of recurrent stroke, but increases the risk of major bleeding events 6.
• However, the use of DAPT in patients with TIA is not widespread, and a retrospective cohort study found that nearly three-fourths of high-risk TIA patients eligible for clopidogrel-aspirin treatment did not receive it 7.

Switching to Plavix (Clopidogrel)

• There is no clear evidence to support switching to Plavix (clopidogrel) in patients who experience a second TIA while on aspirin therapy 3, 4.
• However, clopidogrel may be considered as an alternative antiplatelet therapy for patients who are intolerant of aspirin or have a high risk of cardioembolic events 3, 4.
• The decision to switch to clopidogrel or add it to aspirin should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 5, 6.