What is the recommended loading dose of aspirin (acetylsalicylic acid) and Plavix (clopidogrel) in a patient with acute cerebral vascular accident (CVA)?

Loading Doses of Aspirin and Clavix in Acute Ischemic Stroke

For acute ischemic stroke, administer aspirin 160-325 mg as a single loading dose immediately after excluding intracranial hemorrhage on neuroimaging, and reserve dual antiplatelet therapy (aspirin 160-325 mg plus clopidogrel 300-600 mg loading doses) specifically for minor stroke (NIHSS ≤3) or high-risk TIA patients only. 1, 2, 3

Aspirin Monotherapy for Standard Acute Ischemic Stroke

Loading Dose and Timing:

• Administer aspirin 160-325 mg as a single loading dose after brain imaging excludes intracranial hemorrhage 1, 2
• The loading dose must be given immediately to ensure rapid and complete inhibition of thromboxane A2-dependent platelet aggregation 2
• Critical timing consideration: If the patient received IV alteplase (tPA), delay aspirin until 24 hours post-thrombolysis to minimize hemorrhagic risk 1, 4

Alternative Routes for Dysphagia:

• Rectal aspirin 325 mg daily is an acceptable alternative if oral administration is not possible 1, 2
• Enteral tube administration of aspirin 81 mg daily can be used 1
• Avoid enteric-coated aspirin for loading doses as it has slower onset of action 2, 4

Maintenance Dosing:

• Continue aspirin 75-100 mg daily for long-term secondary prevention after the acute phase 1, 2

Dual Antiplatelet Therapy (DAPT) for Minor Stroke or High-Risk TIA

Patient Selection Criteria:

• Minor ischemic stroke (typically NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4) 2, 3
• Must present within 24 hours of symptom onset 2
• Noncardioembolic mechanism confirmed 2

Loading Dose Protocol:

• Aspirin: 160-325 mg loading dose 2, 3, 4
• Clopidogrel: 300-600 mg loading dose 2, 3, 4
• Administer both agents within 12-24 hours of symptom onset after excluding intracranial hemorrhage 2, 3, 4

Rationale for Clopidogrel Loading:

• Standard 75 mg daily dosing of clopidogrel takes approximately 5 days to achieve maximal platelet inhibition 2, 3, 4
• The loading dose (300-600 mg) rapidly inhibits platelet aggregation, providing immediate antiplatelet effect critical for acute stroke management 3, 4

Maintenance and Duration:

• Continue clopidogrel 75 mg daily plus aspirin 75-100 mg daily for exactly 21 days 2, 3
• After 21 days, transition to single antiplatelet therapy (either aspirin 75-100 mg daily or clopidogrel 75 mg daily) 2, 3
• Do not extend DAPT beyond 90 days as this significantly increases major hemorrhage risk (hazard ratio 2.22-2.32) without additional benefit 2

Evidence Supporting Different Approaches

Why Not DAPT for All Strokes:

• The American College of Chest Physicians guidelines note that dual antiplatelet therapy was not proven successful in stable patients at high risk for atherothrombotic events or in patients after recent ischemic stroke or TIA when compared to aspirin alone 1
• The POINT trial (2018) demonstrated that while DAPT reduced major ischemic events (5.0% vs 6.5%, HR 0.75), it also increased major hemorrhage (0.9% vs 0.4%, HR 2.32) 5
• Most benefit occurs in the first week after the initial event, justifying the limited 21-day duration 2

Aspirin Dose-Response Data:

• A 2016 study of 3,802 patients demonstrated that higher loading doses (160-325 mg) were significantly associated with favorable clinical outcomes (OR 1.49,95% CI 1.17-1.89) compared to lower doses, though with increased minor bleeding 6
• The COMMIT trial used aspirin 162 mg daily without a clopidogrel loading dose and showed safety in acute MI, but this approach has been superseded by loading dose strategies in stroke 1

Critical Safety Considerations

Mandatory Pre-Treatment Requirements:

• Always rule out intracranial hemorrhage on neuroimaging before administering any antiplatelet loading dose 2, 3, 4
• Perform dysphagia screening before oral administration 1

Bleeding Risk with DAPT:

• DAPT increases moderate-to-severe bleeding risk compared to aspirin monotherapy 4
• The absolute increase in major hemorrhage is 0.5% (23/2432 vs 10/2449 patients in POINT trial) 5
• Monitor closely for both minor and major bleeding complications 4

Contraindications:

• Do not use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible patients 2
• Do not use glycoprotein IIb/IIIa inhibitors as these are potentially harmful in acute ischemic stroke 2

Common Pitfalls to Avoid

• Do not delay aspirin beyond 48 hours as benefit is time-dependent with maximum efficacy when started early 2
• Do not use DAPT routinely for all strokes—reserve it specifically for minor stroke or high-risk TIA 2, 5
• Do not continue DAPT beyond 21-30 days for routine secondary prevention as this increases hemorrhage risk without benefit 2
• Do not use higher clopidogrel loading doses (600 mg) validated for PCI patients as the stroke/TIA population uses 300-600 mg range 3
• Never discontinue aspirin after the acute phase unless contraindicated or switching to anticoagulation for cardioembolic etiology 2