Is dual antiplatelet therapy (using medications such as aspirin and a P2Y12 inhibitor like clopidogrel) or anticoagulation (using medications such as warfarin or a novel oral anticoagulant) indicated for a patient who has experienced a stroke due to vertebral artery occlusion?

Antiplatelet Therapy Over Anticoagulation for Vertebral Artery Occlusion Stroke

For patients with ischemic stroke due to vertebral artery occlusion, antiplatelet therapy is indicated over anticoagulation, with dual antiplatelet therapy (aspirin plus clopidogrel) recommended for 21-90 days if the stroke is minor (NIHSS ≤3) or the patient had a high-risk TIA, followed by single antiplatelet therapy indefinitely. 1

Primary Treatment Recommendation

Antiplatelet agents are recommended over oral anticoagulation for noncardioembolic ischemic stroke, including vertebral artery occlusion (Class I, Level A recommendation). 1 This represents the highest level of guideline evidence, with the 2021 AHA/ASA guidelines explicitly stating that antiplatelet therapy is indicated in preference to oral anticoagulation to reduce recurrent ischemic stroke risk while minimizing bleeding complications. 1

The WARSS trial specifically evaluated this question in patients with large-artery stenosis or occlusion, including extracranial vertebral disease, and found no benefit of warfarin over aspirin after 2 years of follow-up. 1

Acute Phase: Dual Antiplatelet Therapy Protocol

For patients presenting with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) due to vertebral artery occlusion:

• Initiate dual antiplatelet therapy within 12-24 hours after excluding intracranial hemorrhage on neuroimaging 1, 2
• Loading doses: Aspirin 160-325 mg PLUS clopidogrel 300-600 mg 2, 3
• Maintenance: Aspirin 81 mg daily PLUS clopidogrel 75 mg daily 1, 2
• Duration: Continue for 21-90 days (optimal duration is 21 days based on pooled analysis) 1, 2, 4

The POINT trial demonstrated that dual antiplatelet therapy reduces major ischemic events by 25% (5.0% vs 6.5%, HR 0.75) in minor stroke/high-risk TIA patients, with most benefit occurring in the first week. 3 While major hemorrhage risk increases (0.9% vs 0.4%, HR 2.32), the number needed to harm is 258, making the benefit-to-risk ratio favorable during this acute period. 4, 3

Long-Term Maintenance: Single Antiplatelet Therapy

After completing 21-90 days of dual antiplatelet therapy, transition to single antiplatelet therapy indefinitely with one of the following options:

• Aspirin 75-100 mg daily (first-line) 1, 2
• Clopidogrel 75 mg daily (equally effective alternative) 1, 2
• Aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily (acceptable alternative) 1

All three regimens have Class I, Level A evidence for secondary stroke prevention in noncardioembolic stroke. 1

Why Not Anticoagulation?

Multiple lines of evidence argue against anticoagulation for vertebral artery occlusion:

• No superiority over antiplatelet therapy: The WARSS trial found no benefit of warfarin over aspirin in large-artery stenosis/occlusion subgroups 1
• Increased bleeding risk: Anticoagulation carries higher hemorrhagic complications without proven efficacy benefit in this population 1
• Guideline consensus: The 2021 AHA/ASA guidelines give antiplatelet therapy a Class I recommendation while noting insufficient data to recommend anticoagulation over antiplatelet therapy for vertebrobasilar disease 1

For vertebrobasilar dolichoectasia specifically (a related condition), case series suggest antithrombotic therapy lowers recurrent ischemic events compared to natural history, but no prospective trials demonstrate clear benefit of anticoagulation over antiplatelet therapy. 1

Critical Pitfalls to Avoid

• Do NOT continue dual antiplatelet therapy beyond 90 days - bleeding risk outweighs benefit with prolonged use (HR for major hemorrhage 2.22-2.32) 1, 2, 4
• Do NOT use anticoagulation routinely unless there is a separate cardioembolic indication (e.g., atrial fibrillation) 1
• Do NOT delay dual antiplatelet therapy - maximum benefit occurs when initiated within 12-24 hours of symptom onset 1, 2
• Do NOT skip the loading doses in acute settings - standard 75 mg clopidogrel dosing takes approximately 5 days to achieve maximal platelet inhibition 2

Special Considerations

For patients with moderate stroke (NIHSS ≤5) or symptomatic vertebral artery stenosis ≥30%, ticagrelor 180 mg loading dose plus aspirin followed by ticagrelor 90 mg twice daily plus aspirin for 30 days may be considered, though this carries increased bleeding risk including intracranial hemorrhage. 1

The CADISS trial in cervical artery dissection (including vertebral dissection) found no difference between antiplatelet therapy and anticoagulation for preventing recurrent stroke, with only 2.5% recurrent stroke rate at 1 year regardless of treatment. 5 This supports the preference for antiplatelet therapy given its lower bleeding risk profile.