What is the recommended timing and dosage for initiating antiplatelet therapy with aspirin (acetylsalicylic acid) in patients with ischemic stroke in the Intensive Care Unit (ICU)?

Antiplatelet Initiation After Stroke in ICU

Primary Recommendation

Initiate aspirin 160-325 mg within 24-48 hours of acute ischemic stroke onset in ICU patients, with administration delayed to 24 hours post-thrombolysis if IV alteplase was given. 1

Timing of Initiation

• Start aspirin within 24-48 hours of symptom onset for maximum benefit in reducing early recurrent stroke and mortality 1, 2
• For patients who received IV alteplase (tPA): delay aspirin administration until 24 hours after thrombolysis to minimize hemorrhagic risk, though earlier administration may be considered if compelling indications exist 1
• For patients NOT receiving thrombolysis: initiate aspirin immediately after intracranial hemorrhage is excluded on neuroimaging 3

Dosing Strategy

Loading Dose

• Administer 160-325 mg aspirin as a single loading dose to achieve rapid and complete inhibition of platelet aggregation 1, 3, 4
• The American Heart Association specifically supports doses between 160-300 mg based on large clinical trial data 1, 4
• Avoid enteric-coated formulations for loading as they have slower onset of action 3

Maintenance Dose

• Continue with 75-100 mg daily for long-term secondary prevention after the acute phase 1
• Lower maintenance doses (75-100 mg) are equally effective as higher doses (283 mg) with fewer adverse effects 5

Route of Administration

• Oral route is preferred if the patient can swallow safely 4
• Rectal suppository (325 mg) or nasogastric tube (81 mg) are reasonable alternatives for patients with impaired swallowing 1, 3

Special Consideration: Minor Stroke or High-Risk TIA

For patients with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), initiate dual antiplatelet therapy (DAPT) instead of aspirin alone:

• Loading dose: aspirin 160-325 mg PLUS clopidogrel 300-600 mg 6, 3
• Maintenance: aspirin 81 mg daily PLUS clopidogrel 75 mg daily 6, 3
• Duration: continue DAPT for exactly 21 days (up to maximum 30 days), then transition to single antiplatelet therapy 1, 6
• Timing: initiate ideally within 12-24 hours of symptom onset for maximum benefit 1, 3
• Critical warning: DAPT beyond 21-30 days significantly increases major bleeding risk (hazard ratio 2.22-2.32) without additional benefit 6

Contraindications to Early Aspirin

Do NOT use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible patients - this delays definitive treatment and worsens outcomes 1

Common Pitfalls to Avoid

• Do not delay aspirin beyond 48 hours - the benefit is time-dependent, with maximum efficacy when started early 1, 2
• Do not use DAPT in moderate-to-severe strokes (NIHSS >3) - use aspirin monotherapy instead as bleeding risk outweighs benefit 6
• Do not continue DAPT beyond 21-30 days - hemorrhagic complications increase substantially after this period 6
• Do not use glycoprotein IIb/IIIa inhibitors (abciximab) - these are potentially harmful in acute ischemic stroke 1
• Ensure neuroimaging excludes hemorrhage before any antiplatelet administration 3

Gastrointestinal Protection

• Consider proton pump inhibitors for patients with risk factors for GI bleeding (history of GI hemorrhage, anticoagulant use, coagulopathy) when initiating antiplatelet therapy 6

Evidence Quality

The recommendation for early aspirin (160-325 mg within 48 hours) is supported by Grade 1A evidence from two large randomized controlled trials involving over 40,000 patients, demonstrating 13 fewer deaths or dependencies per 1000 patients treated 1, 2. The 2018 AHA/ASA guidelines provide the most current Class I, Level A recommendation for this practice 1.