What are the doses of antiplatelet and anticoagulant medications for a patient with acute stroke not eligible for thrombolysis (tissue plasminogen activator)?

Antiplatelet and Adjunctive Medication Dosing for Acute Ischemic Stroke (Not Eligible for Thrombolysis)

For patients with acute ischemic stroke who are not eligible for thrombolysis, initiate aspirin 160-325 mg as a single loading dose within 48 hours of symptom onset, followed by specific dosing regimens based on stroke severity. 1

Immediate Acute Phase Management (Within 48 Hours)

For Minor Stroke (NIHSS ≤ 3) or High-Risk TIA (ABCD2 ≥ 4):

Loading Doses:

• Aspirin: 160-325 mg as a single loading dose 1
• Clopidogrel: 300-600 mg as a single loading dose (300 mg per CHANCE trial, 600 mg per POINT trial) 1

Maintenance Dual Antiplatelet Therapy (DAPT) for 21 Days:

• Aspirin: 81 mg daily 1
• Clopidogrel: 75 mg daily 1

After 21 Days - Transition to Single Agent:

• Either aspirin 81 mg daily OR clopidogrel 75 mg daily 1

For Mild-Moderate Stroke (NIHSS ≤ 5) or High-Risk TIA (ABCD2 ≥ 4):

Alternative DAPT Regimen:

Loading Doses:

• Aspirin: 300-325 mg as a single loading dose 1
• Ticagrelor: 180 mg as a single loading dose 1

Maintenance DAPT for 30 Days:

• Aspirin: 75-100 mg daily 1
• Ticagrelor: 90 mg twice daily 1

After 30 Days - Transition to Single Agent:

• Either aspirin 81 mg daily OR clopidogrel 75 mg daily 1

For Moderate-Severe Stroke (NIHSS > 5) or Non-Cardioembolic Stroke:

Acute Phase:

• Aspirin: 160-325 mg as a single loading dose within 48 hours 1, 2

Long-Term Maintenance (Single Agent):

• Aspirin: 81-325 mg daily OR 1
• Clopidogrel: 75 mg daily (preferred over aspirin) OR 1
• Aspirin/Extended-Release Dipyridamole: 25 mg/200 mg twice daily (preferred over aspirin alone) 1

The 2023 World Stroke Organization guidelines prioritize clopidogrel or aspirin/dipyridamole combination over aspirin monotherapy for long-term secondary prevention based on superior efficacy. 1

Venous Thromboembolism Prophylaxis (For Patients with Restricted Mobility)

Pharmacologic Options (Preferred):

• Low-Molecular-Weight Heparin (LMWH) at prophylactic doses (preferred over unfractionated heparin) 1
• Unfractionated Heparin (UFH) at prophylactic doses subcutaneously 1

Mechanical Option:

• Intermittent pneumatic compression devices (if contraindications to anticoagulation exist) 1

Timing: Initiate VTE prophylaxis as early as possible, ideally within 24 hours of admission, after ruling out intracranial hemorrhage. 1

Additional Adjunctive Medications

Blood Pressure Management:

• Target systolic blood pressure < 140 mmHg for patients with intracranial atherosclerotic stenosis (50-99%) 1

Lipid-Lowering Therapy:

• High-dose statin therapy is recommended for patients with intracranial atherosclerotic stenosis (50-99%) 1

Critical Timing Considerations

The evidence strongly supports initiating antiplatelet therapy within 12-24 hours for minor stroke/high-risk TIA to maximize benefit. 1 The POINT trial demonstrated that most ischemic events occur during the first week after the initial event, making early initiation crucial. 3

Important Caveats

Hemorrhage Risk with DAPT: The POINT trial showed that while DAPT reduces major ischemic events (5.0% vs 6.5%), it increases major hemorrhage risk (0.9% vs 0.4%). 3 This is why DAPT is limited to 21-30 days and reserved for minor strokes or high-risk TIAs.

Swallowing Impairment: If the patient cannot swallow, use rectal aspirin 325 mg daily OR aspirin 81 mg daily via enteral tube OR clopidogrel 75 mg daily via enteral tube. 1

Cardioembolic Stroke: If atrial fibrillation is identified, transition to oral anticoagulation (not antiplatelet therapy) within 1-2 weeks after stroke onset. 1