What is the preferred initial treatment, aspirin or anticoagulation (anticoagulant), for a patient presenting with acute ischemic stroke?

Aspirin Over Anticoagulation for Acute Ischemic Stroke

For patients with acute ischemic stroke, aspirin 160-325 mg should be initiated within 48 hours rather than therapeutic anticoagulation, as aspirin reduces early recurrent stroke and death without the increased bleeding risk associated with anticoagulation. 1, 2

Primary Treatment Algorithm

First-Line Therapy: Aspirin

• Administer aspirin 160-325 mg within 24-48 hours of stroke onset after intracranial hemorrhage has been ruled out on neuroimaging 1, 2, 3
• This loading dose achieves rapid and complete inhibition of thromboxane A2-dependent platelet aggregation 2
• Aspirin prevents approximately 10 deaths and early recurrent strokes per 1,000 patients treated, with a number needed to treat of 100 1, 4

Why NOT Therapeutic Anticoagulation

• The American College of Chest Physicians explicitly recommends AGAINST therapeutic parenteral anticoagulation in acute ischemic stroke (Grade 1A evidence) 1
• Urgent anticoagulation with heparin, low-molecular-weight heparin, or heparinoids does NOT improve outcomes and significantly increases bleeding risk, including hemorrhagic transformation 1, 3, 5
• The evidence shows that therapeutic anticoagulation has "as many potential benefits as risks" with high-dose heparin being harmful 5

Timing Considerations

Delay Aspirin If Thrombolysis Given

• If IV alteplase (r-tPA) was administered, delay aspirin for 24 hours post-thrombolysis to minimize hemorrhagic risk 2, 3
• For patients presenting within 3 hours of symptom onset, IV r-tPA 0.9 mg/kg (maximum 90 mg) is the definitive first-line treatment, NOT aspirin 3

Aspirin Administration Window

• The benefit of aspirin is time-dependent with maximum efficacy when started early 2
• Do NOT delay aspirin beyond 48 hours once hemorrhage is excluded 1, 2

Special Circumstances Where Prophylactic Anticoagulation May Be Used

VTE Prophylaxis Only

• For patients with restricted mobility, prophylactic-dose subcutaneous heparin (UFH or LMWH) may be used starting between days 2-4 for venous thromboembolism prevention, NOT for stroke treatment 1
• This is prophylactic dosing (5,000 units subcutaneous twice daily), NOT therapeutic anticoagulation 1

High Thrombotic Risk Exceptions

• Low-dose heparin may be justified for patients with emboligenic heart disease, tight carotid stenosis, or high risk of pulmonary embolism, but this remains controversial 5
• Higher-dose heparin is only warranted for the rare patient with exceptionally high thrombotic risk 5

Transition to Long-Term Therapy

After Acute Phase (Beyond 48 Hours)

• Continue aspirin 75-100 mg daily for long-term secondary prevention 1, 2, 6
• Alternative single antiplatelet agents include clopidogrel 75 mg daily or aspirin/extended-release dipyridamole 25 mg/200 mg twice daily 1, 6

Consider Dual Antiplatelet Therapy for Minor Stroke

• For minor stroke (NIHSS ≤3-5) or high-risk TIA (ABCD2 score ≥4), initiate dual antiplatelet therapy with aspirin PLUS clopidogrel for exactly 21 days, then transition to single antiplatelet therapy 2, 7
• Loading doses: clopidogrel 300-600 mg + aspirin 160-325 mg within 24 hours 2
• Maintenance: clopidogrel 75 mg + aspirin 75-100 mg daily for 21 days 2

Critical Pitfalls to Avoid

• Never use aspirin as a substitute for thrombolysis in eligible patients presenting within the treatment window 2, 3
• Never administer aspirin within 24 hours of r-tPA due to increased bleeding risk 2, 3
• Never use therapeutic anticoagulation routinely in acute ischemic stroke—the evidence strongly opposes this practice 1, 3
• Do NOT use glycoprotein IIb/IIIa inhibitors (abciximab), as they are potentially harmful in acute ischemic stroke 2

Evidence Quality

The recommendation for aspirin over anticoagulation is supported by Grade 1A evidence from two large randomized controlled trials involving over 40,000 patients 1, 2, demonstrating 13 fewer deaths or dependencies per 1,000 patients treated with aspirin 2. The recommendation against therapeutic anticoagulation is equally strong (Grade 1A against) 1.