What is the initial management of antiplatelet therapy after an ischemic stroke?

Antiplatelet Initiation After Ischemic Stroke

For most patients with acute ischemic stroke, initiate aspirin 160-325 mg orally within 24-48 hours of symptom onset; however, for minor stroke (NIHSS ≤3) or high-risk TIA, start dual antiplatelet therapy with aspirin plus clopidogrel within 12-24 hours after excluding intracranial hemorrhage on neuroimaging. 1, 2

Initial Assessment and Timing

The first critical decision point is whether the patient received or is eligible for thrombolytic therapy (IV alteplase) or mechanical thrombectomy:

• If thrombolysis was administered: Do not give aspirin or any antiplatelet agent for 24 hours after IV alteplase due to increased hemorrhage risk (Class III, Level of Evidence A) 1, 3
• If no thrombolysis: Proceed immediately with antiplatelet selection based on stroke severity 1, 2

Antiplatelet Selection Algorithm

For Minor Stroke (NIHSS ≤3) or High-Risk TIA

Initiate dual antiplatelet therapy (DAPT) within 12-24 hours after excluding intracranial hemorrhage on CT or MRI: 1, 2

• Loading doses: Aspirin 160-325 mg + clopidogrel 300-600 mg 2, 4
• Maintenance: Aspirin 100 mg daily + clopidogrel 75 mg daily for 21-30 days only 1, 2, 4
• After 21-30 days: Transition to single antiplatelet therapy (clopidogrel 75 mg daily preferred) for long-term secondary prevention 2, 4

The evidence supporting this approach is robust. A 2023 Chinese trial (INSPIRES) demonstrated that clopidogrel plus aspirin initiated within 72 hours reduced new stroke risk by 21% (7.3% vs 9.2%, HR 0.79, P=0.008) compared to aspirin alone, though with a small increase in moderate-to-severe bleeding (0.9% vs 0.4%) 5. The benefit of DAPT is time-dependent, with greatest efficacy when started within 24 hours 1, 2.

For Moderate-to-Severe Stroke (NIHSS >3)

Initiate aspirin monotherapy 160-325 mg within 24-48 hours: 1, 2, 3

• Aspirin can be administered orally, via nasogastric tube, or rectally if swallowing is impaired 2
• This provides a modest but statistically significant reduction in mortality and recurrent stroke (approximately 10 fewer deaths and recurrent strokes per 1,000 patients treated) 1, 6
• The primary benefit is prevention of early recurrent ischemic stroke, not limitation of the initial stroke's neurological consequences 1

Critical Safety Considerations

Absolute contraindications to aspirin include: 2

• Active pathological bleeding (peptic ulcer, intracranial hemorrhage)
• Known aspirin allergy

For clopidogrel, avoid concomitant use with: 4, 7

• Omeprazole or esomeprazole (CYP2C19 inhibitors that reduce clopidogrel effectiveness)
• Consider alternative proton pump inhibitors if gastric protection is needed

Common pitfall: Do not delay aspirin beyond 48 hours in patients not receiving thrombolysis, as the window for maximum benefit closes rapidly 4, 6. The reduction in early recurrent stroke is most pronounced when treatment begins immediately.

Agents NOT Recommended

• Clopidogrel monotherapy: Not established for acute stroke treatment (Class IIb, Level of Evidence C) 1, 3
• Intravenous glycoprotein IIb/IIIa inhibitors (abciximab, tirofiban, eptifibatide): Not recommended outside clinical trials due to increased bleeding risk without proven benefit (Class III, Level of Evidence B) 1
• Ticagrelor: Not recommended over aspirin in acute minor stroke (Class III, Level of Evidence B) 1

Special Clinical Scenarios

For symptomatic intracranial stenosis: Use DAPT (aspirin + clopidogrel) combined with aggressive risk factor management including systolic blood pressure <140 mmHg and high-dose statin therapy 4

For atrial fibrillation: Use aspirin in the acute phase, then transition to oral anticoagulation for long-term secondary prevention (timing of anticoagulation initiation depends on stroke size and hemorrhagic transformation risk) 2

For cervical arterial dissection: Antiplatelet therapy is reasonable, as systematic reviews show no significant difference between antiplatelet therapy and anticoagulation 2

Duration of Dual Antiplatelet Therapy

Critical timing: DAPT should be limited to 21-30 days maximum, then transition to single antiplatelet therapy 1, 2, 4. A 2016 meta-analysis demonstrated that short-term DAPT (≤3 months) reduced ischemic stroke recurrence by 41% without increasing intracranial hemorrhage, while prolonged DAPT (≥1 year) increased major bleeding and intracranial hemorrhage risk despite only modest additional benefit 8.

Premature discontinuation of antiplatelet therapy increases cardiovascular event risk, so ensure patient understanding and adherence 4.