What is the role of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, such as clopidogrel, in patients with a history of ischemic stroke?

Dual Antiplatelet Therapy in Ischemic Stroke

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel should be used for a short duration (21-30 days) in patients with minor ischemic stroke or high-risk TIA, followed by indefinite single antiplatelet therapy for secondary stroke prevention.

Patient Selection for DAPT

DAPT with aspirin and clopidogrel is indicated for:

• Patients with minor ischemic stroke (NIHSS score ≤3-5) 1
• High-risk TIA patients (ABCD2 score ≥4) 1
• Treatment should be initiated within 24-72 hours of symptom onset 2, 3

DAPT is not recommended for:

• Patients with hemorrhagic stroke 1
• Patients with high bleeding risk 1
• Patients with cardioembolic stroke (e.g., atrial fibrillation) 4, 1

Efficacy and Safety of DAPT

Efficacy

• DAPT reduces the risk of recurrent stroke by 24% compared to aspirin alone 1, 5
• The number needed to treat is 92 patients to prevent one stroke 1
• Most benefit occurs within the first 21 days after the initial event 2
• In the POINT and CHANCE trials, DAPT reduced major ischemic events at 90 days (6.5% vs 9.1%) compared with aspirin alone 2

Safety Considerations

• DAPT increases bleeding risk compared to single antiplatelet therapy 5, 6
• Major bleeding occurs in 0.9% of DAPT patients vs 0.4% with aspirin alone 3
• Number needed to harm is 258 for intracranial bleeding and 113 for major bleeding 5
• Risk factors for bleeding include older age, more severe stroke, history of bleeding, and longer DAPT duration 1

Recommended Regimen

Initial Loading Dose

• Aspirin 160-325mg plus clopidogrel 300-600mg 1

Maintenance Dose

• Aspirin 81mg daily plus clopidogrel 75mg daily 1

Duration

• Short-term DAPT (21-30 days) is recommended 1, 2
• Extended DAPT beyond 90 days increases bleeding risk without additional stroke prevention benefit 1, 5
• After DAPT completion, transition to indefinite single antiplatelet therapy (aspirin 75-100mg daily or clopidogrel 75mg daily) 4, 1

Timing of Initiation

The maximum benefit occurs when DAPT is initiated within 24 hours of symptom onset 1, but recent evidence shows benefit when initiated within 72 hours 3. The INSPIRES trial demonstrated that DAPT initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days (7.3% vs 9.2%) compared to aspirin alone, though with a higher risk of moderate-to-severe bleeding (0.9% vs 0.4%) 3.

Monitoring and Management

• Monitor for bleeding complications during DAPT treatment 1, 7
• Consider gastric protection in patients at high risk of gastrointestinal bleeding 4, 1
• Educate patients about the planned duration of DAPT and the transition to monotherapy 1

Special Considerations

For patients with a history of noncardioembolic ischemic stroke or TIA, long-term treatment options include:

• Aspirin (75-100mg daily)
• Clopidogrel (75mg daily)
• Aspirin/extended-release dipyridamole (25mg/200mg twice daily)
• Cilostazol (100mg twice daily) 4

Of these options, clopidogrel or aspirin/extended-release dipyridamole are suggested over aspirin or cilostazol for long-term secondary prevention 4.

Common Pitfalls to Avoid

1. Extended DAPT duration: Continuing DAPT beyond 30 days increases bleeding risk without additional benefit 1, 5, 2
2. Delayed initiation: Maximum benefit occurs when DAPT is started within 24-72 hours of symptom onset 1, 3
3. Using DAPT in cardioembolic stroke: DAPT is not recommended for patients with atrial fibrillation or other cardioembolic sources 4, 1
4. Overlooking bleeding risk: Always assess bleeding risk before initiating DAPT 1
5. Abrupt discontinuation: Patients should not discontinue clopidogrel without discussing with their healthcare provider 7

By following these evidence-based recommendations, clinicians can optimize the use of dual antiplatelet therapy to reduce recurrent stroke risk while minimizing bleeding complications in appropriate patients.