What are the guidelines for antiplatelet (antiplatelet) therapy in patients with a history of ischemic stroke?

Antiplatelet Guidelines for Ischemic Stroke Secondary Prevention

For patients with noncardioembolic ischemic stroke or TIA, initiate dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 12-24 hours of symptom onset for minor stroke or high-risk TIA, continue for 21-30 days, then transition to single antiplatelet therapy with clopidogrel 75 mg daily for long-term prevention. 1, 2

Acute Phase Management (First 48 Hours)

Minor Stroke or High-Risk TIA

• Start DAPT immediately (within 12-24 hours) after excluding intracranial hemorrhage on neuroimaging 1, 2
• Loading doses: Aspirin 160-325 mg plus clopidogrel 300-600 mg on day 1 1, 2
• Maintenance: Aspirin 81 mg daily plus clopidogrel 75 mg daily for 21-30 days 1, 2
• Alternative regimen: Aspirin 75-100 mg daily plus ticagrelor 90 mg twice daily (loading: aspirin 300-325 mg plus ticagrelor 180 mg) for 30 days 2

Moderate-to-Severe Stroke

• Aspirin monotherapy only (160-300 mg daily) initiated within 24-48 hours for patients not receiving thrombolysis or thrombectomy 1, 3
• Do not delay aspirin beyond 48 hours—early administration reduces early recurrent stroke and improves long-term outcomes 1, 3

Long-Term Secondary Prevention (After 21-30 Days)

First-Line Options for Noncardioembolic Stroke

Clopidogrel 75 mg daily is the preferred single antiplatelet agent for long-term secondary prevention 1, 2, 4

Alternative acceptable options include: 5, 2

• Aspirin 75-100 mg daily plus extended-release dipyridamole 200 mg twice daily
• Aspirin 75-100 mg daily alone
• Cilostazol 100 mg twice daily

Critical Safety Rule

Never continue DAPT (aspirin plus clopidogrel) beyond 21-30 days for routine secondary prevention—this increases bleeding risk without additional benefit (Class III recommendation) 5, 2, 4

Special Clinical Scenarios

Symptomatic Intracranial Stenosis (Moderate-to-Severe)

• DAPT with aspirin plus clopidogrel for 90 days, then transition to aspirin monotherapy 6
• Must combine with: systolic blood pressure target <140 mmHg, high-dose statin therapy, and at least moderate physical activity 1

Embolic Stroke of Undetermined Source (ESUS)

• Use antiplatelet therapy, NOT oral anticoagulants 1, 4
• Follow the same long-term antiplatelet regimen as noncardioembolic stroke 1

Cardioembolic Stroke with Atrial Fibrillation

• Oral anticoagulation is mandatory—antiplatelet therapy is inadequate 4, 6
• Direct oral anticoagulants (DOACs) preferred over warfarin 4
• Dabigatran 150 mg twice daily is preferred over warfarin (target INR 2.0-3.0) 4

Arterial Dissection

• Either antiplatelet therapy or anticoagulation for 3-6 months is reasonable 5
• Beyond 3-6 months, long-term antiplatelet therapy is reasonable 5

Patent Foramen Ovale (PFO)

• Antiplatelet therapy is reasonable for patients with ischemic stroke/TIA and PFO 5
• Warfarin is reasonable only for high-risk patients with underlying hypercoagulable state or evidence of venous thrombosis 5

Antiphospholipid Antibody Syndrome

• For cryptogenic stroke with positive antiphospholipid antibodies: antiplatelet therapy is reasonable 5
• For patients meeting full criteria for antiphospholipid antibody syndrome: oral anticoagulation with target INR 2.0-3.0 is reasonable 5

Critical Caveats and Pitfalls

Drug Interactions

Avoid concomitant use of clopidogrel with omeprazole or esomeprazole—these CYP2C19 inhibitors reduce clopidogrel's effectiveness 1

Dosing Considerations

• Do not use aspirin >325 mg daily long-term—side effects increase without additional benefit 2
• For patients <60 kg: consider lowering clopidogrel maintenance dose to 5 mg daily due to increased bleeding risk 7
• For patients ≥75 years: use antiplatelet therapy generally not recommended except in high-risk situations (diabetes or history of MI) 7

Contraindications to Specific Agents

Prasugrel is contraindicated in patients with prior TIA or stroke—it increases stroke risk (6.5% vs 1.2% with clopidogrel) including intracranial hemorrhage 7

Bleeding Risk Factors

Monitor closely for bleeding in patients with: 7

• Recent trauma or surgery
• Active peptic ulcer disease
• Severe hepatic impairment
• Moderate to severe renal impairment
• Concomitant use of NSAIDs, oral anticoagulants, or fibrinolytic agents

Adherence

Premature discontinuation of antiplatelet therapy increases the risk of subsequent cardiovascular events—ensure medication adherence at every visit 1, 4

Comparative Effectiveness

The 2021 AHA/ASA guidelines note that head-to-head comparisons are limited, but available evidence suggests: 5

• Clopidogrel provides superior efficacy compared to aspirin alone for reducing all strokes, cardiovascular events, and intracranial hemorrhage 8
• Cilostazol appears most effective (OR 0.51 for stroke reduction) but data are limited to Asian populations 8
• Aspirin plus extended-release dipyridamole is superior to aspirin alone (OR 0.65 vs 0.79) 8