What medication changes are recommended for stroke prophylaxis in a patient who experienced an ischemic stroke while on Aspirin (acetylsalicylic acid) and Plavix (clopidogrel)?

From the Guidelines

For a patient who experienced an ischemic stroke while on dual antiplatelet therapy (Aspirin and Plavix/clopidogrel), I strongly recommend discontinuing the combination of clopidogrel and aspirin due to the increased risk of hemorrhage and lack of significant reduction in major CV events, as evidenced by the 2010 expert consensus document 1. The treatment failure on current therapy suggests the need for a different approach, focusing on minimizing morbidity, mortality, and improving quality of life.

Key Considerations

• The combination of clopidogrel and aspirin is not recommended for routine secondary prevention after ischemic stroke or TIA, as it increases the risk of hemorrhage without providing significant benefits 1.
• Options for alternative antiplatelet therapy include aspirin monotherapy, the combination of aspirin and extended-release dipyridamole, or clopidogrel monotherapy, with the selection individualized based on 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, and alternative strategies should be considered 1.

Recommendations

• Discontinue the combination of clopidogrel and aspirin and consider switching to a single antiplatelet agent, such as aspirin or clopidogrel, to minimize the risk of hemorrhage while maintaining some level of stroke prophylaxis.
• Intensify other stroke risk factor management, including optimizing blood pressure control, achieving tight glycemic control if diabetic, and ensuring LDL cholesterol is below 70 mg/dL with high-intensity statin therapy.
• Consider consulting with a neurologist or vascular specialist to reassess the antithrombotic regimen and determine the best course of action for the individual patient.

From the FDA Drug Label

In TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel), patients with a history of TIA or ischemic stroke (>3 months prior to enrollment) had a higher rate of stroke on prasugrel tablets (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage [ICH]) than on clopidogrel (1. 2%; all thrombotic). Patients who experience a stroke or TIA while on prasugrel tablets generally should have therapy discontinued [see Adverse Reactions (6.1) and Clinical Studies (14)].

The patient experienced an ischemic stroke while on Aspirin and Plavix (clopidogrel).

• Discontinue the current antiplatelet therapy (Aspirin and Plavix) is not explicitly recommended in the label for this scenario, but
• Prasugrel is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke, which applies to this patient.
• No alternative medication is recommended in the label for stroke prophylaxis in this scenario. 2 2

From the Research

Medication Changes for Stroke Prophylaxis

The following medication changes are recommended for stroke prophylaxis in a patient who experienced an ischemic stroke while on Aspirin (acetylsalicylic acid) and Plavix (clopidogrel):

• Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for a short duration (≤ 1 month) is recommended for patients with minor acute noncardioembolic ischemic stroke or high-risk TIA, as it is associated with a lower risk of recurrent stroke and a lower risk of bleeding compared to long-term DAPT 3, 4.
• The combination of ticagrelor and aspirin for 30 days may be considered as an alternative to clopidogrel and aspirin, as it has been shown to reduce the risk of stroke or death within 30 days in patients with mild-to-moderate acute noncardioembolic ischemic stroke or TIA 5.
• Single-antiplatelet therapy (SAPT) with aspirin, aspirin/extended-release dipyridamole, or clopidogrel is recommended for long-term secondary stroke prevention in patients with non-cardioembolic ischemic stroke or TIA 6, 4.
• Cilostazol or ticagrelor may be considered as alternative options for patients with intracranial stenosis, as they may be more effective than aspirin or clopidogrel in this population 4, 7.

Key Considerations

When selecting antiplatelet therapy, the following factors should be considered:

• Patient compliance and drug tolerance
• Risk of bleeding and intracranial hemorrhage
• Presence of intracranial stenosis or other high-risk features
• History of cardiovascular disease or other comorbidities
• Potential interactions with other medications 3, 4, 5, 7