Loading Dose of Antiplatelets in Acute Ischemic Stroke: Indications and Recommended Dosages
A loading dose of antiplatelets is strongly indicated in acute ischemic stroke, with aspirin 160-325 mg recommended for all patients after intracranial hemorrhage is ruled out, and specific dual antiplatelet loading doses recommended for minor stroke or high-risk TIA patients. 1, 2
General Recommendations for Antiplatelet Loading Dose
- For patients with acute ischemic stroke or TIA who were not previously on antiplatelet therapy, a single loading dose of aspirin 160 mg should be administered after ruling out intracranial hemorrhage on neuroimaging 1
- In patients with swallowing difficulties, rectal aspirin 325 mg daily or aspirin 81 mg daily administered via enteral tube are reasonable alternatives to oral intake 1, 2
- The loading dose ensures rapid and complete inhibition of thromboxane A2-dependent platelet aggregation in the acute setting 2
Specific Loading Dose Recommendations for Minor Stroke or TIA
Aspirin + Clopidogrel Regimen
- For patients with minor ischemic stroke (NIHSS ≤ 3) or high-risk TIA (ABCD2 ≥ 4), a loading dose of:
- DAPT should be initiated as early as possible, ideally within 12-24 hours of symptom onset 1, 3
- Continue with clopidogrel 75 mg daily plus aspirin 81 mg daily for 21 days, followed by single antiplatelet therapy 1, 3
Aspirin + Ticagrelor Regimen
- For patients with mild-moderate ischemic stroke (NIHSS ≤ 5) or high-risk TIA (ABCD2 ≥ 4), a loading dose of:
- Continue with aspirin 75-100 mg daily and ticagrelor 90 mg twice daily for 30 days, followed by single antiplatelet therapy 1
Pharmacological Rationale for Loading Doses
- Standard 75 mg daily dosing of clopidogrel does not produce maximal platelet inhibition for approximately 5 days, which is problematic for achieving early treatment effect in acute stroke management 3
- A loading dose of clopidogrel (300-600 mg) rapidly inhibits platelet aggregation, providing immediate antiplatelet effect 3
- Dual antiplatelet therapy with loading doses has been shown to significantly reduce stroke recurrence compared to monotherapy (3.3% vs 5.0%) 4
Important Clinical Considerations
- Always rule out intracranial hemorrhage on neuroimaging before administering any antiplatelet loading dose 1, 3, 2
- Avoid enteric-coated aspirin for the loading dose as it has a slower onset of action 2
- The absolute benefits of antiplatelet therapy substantially outweigh the absolute risks of major bleeding in moderate to high-risk patients with ischemic stroke 2, 5
- For every 1000 patients treated with aspirin, 13 more patients were alive and independent at the end of follow-up, despite a small increase in symptomatic intracranial hemorrhages (2 per 1000) 5, 6
Special Patient Populations
- In patients with moderate to high-grade intracranial atherosclerotic stenosis (50-99%), dual antiplatelet therapy is recommended over stenting 1
- Monitoring of antiplatelet therapy efficacy may be beneficial, as studies have shown that up to 35% of patients on aspirin and 55% of patients on clopidogrel may have suboptimal response 7