In a patient with a malignant cerebral infarct confirmed ischemic on CT/MRI, when should aspirin be started, what dose is recommended, and what are the contraindications?

Aspirin in Malignant Cerebral Infarct

Start aspirin 160–325 mg within 24–48 hours of symptom onset after confirming the absence of intracranial hemorrhage on CT or MRI, but delay administration for at least 24 hours if the patient received IV thrombolysis. 1, 2

Timing of Aspirin Initiation

For Patients Who Did NOT Receive IV Thrombolysis

• Administer aspirin 160–325 mg within 24–48 hours of stroke onset once brain imaging excludes hemorrhagic transformation or intracranial hemorrhage. 1, 2
• The benefit is time-dependent; maximal efficacy occurs when aspirin is started within the first 24–48 hours, with evidence from 40,000 patients showing a reduction of 9 per 1,000 in the risk of further stroke or death. 3
• Do not delay aspirin beyond 48 hours when eligibility criteria are met, as the therapeutic window narrows significantly after this period. 4, 3

For Patients Who Received IV Thrombolysis (Alteplase)

• Delay aspirin for at least 24 hours after thrombolytic administration to minimize the risk of serious intracranial hemorrhage. 1, 5, 2
• Obtain a 24-hour post-thrombolysis CT scan to exclude hemorrhagic transformation before initiating any antiplatelet therapy. 5, 2
• Earlier administration may be considered only when there are compelling cardiac or other vascular indications, but this requires careful risk-benefit assessment. 4

For Patients Who Underwent Mechanical Thrombectomy Alone

• Start aspirin immediately after thrombectomy once brain imaging excludes hemorrhage, with a loading dose of at least 160 mg. 5
• The same 24-hour delay applies if the patient received both thrombectomy and IV thrombolysis. 5

Recommended Aspirin Dose

Loading Dose

• Administer 160–325 mg as the initial loading dose to achieve rapid and complete inhibition of thromboxane A2-dependent platelet aggregation. 1, 4, 2, 6
• The 2018 AHA/ASA guideline endorses this broader range (160–325 mg) because supporting clinical trials used doses within this spectrum. 4
• Use non-enteric coated aspirin formulations for the loading dose, as enteric-coated preparations have a slower onset of action. 4, 5

Maintenance Dose

• Continue with 75–100 mg daily starting on day 2 and maintained indefinitely for secondary stroke prevention. 1, 4, 2
• This maintenance dose provides equivalent efficacy to higher doses (up to 1,500 mg) while minimizing gastrointestinal bleeding risk. 4

Alternative Routes for Patients with Dysphagia

• Aspirin 325 mg rectal suppository daily is a reasonable alternative for patients unable to swallow. 4, 5
• Aspirin 81 mg via enteral feeding tube is another acceptable option. 4, 5

Contraindications to Aspirin in Malignant Infarct

Absolute Contraindications

• Intracranial hemorrhage not excluded on neuroimaging (CT or MRI must be performed first). 1, 4, 2
• Active major bleeding or severe thrombocytopenia. 4
• Known hypersensitivity to aspirin. 4
• Recent IV alteplase administration within the past 24 hours without confirmatory imaging excluding hemorrhagic transformation. 4, 5, 2

Relative Contraindications and High-Risk Features

• Hemorrhagic transformation of the infarct requires careful risk stratification:
  • For non-lobar hemorrhagic transformation with strong antiplatelet indications, restart aspirin at 3–7 days post-hemorrhage if the patient is clinically stable. 2
  • For lobar hemorrhagic transformation or weaker indications, delay aspirin for a minimum of 4–6 weeks. 2
• High-risk features for hemorrhagic complications include lobar location of any hemorrhagic transformation, older age, presence and number of microbleeds on gradient echo MRI, and Apolipoprotein E ε2 or ε4 alleles. 2

Critical Pitfalls to Avoid

• Do NOT use aspirin as a substitute for IV thrombolysis or mechanical thrombectomy in eligible patients, as this delays definitive treatment and worsens outcomes (Class III recommendation). 4, 2
• Do NOT combine aspirin with clopidogrel for treatment of acute malignant infarct unless the stroke is minor (NIHSS ≤3), as dual antiplatelet therapy is not indicated for moderate-to-severe strokes. 4, 2
• Do NOT use glycoprotein IIb/IIIa inhibitors (e.g., abciximab, eptifibatide, tirofiban) in acute ischemic stroke, as they are potentially harmful. 4
• Do NOT skip the 24-hour post-thrombolysis imaging if the patient received IV alteplase; hemorrhage must be excluded before starting any antiplatelet therapy. 5, 2

Evidence Supporting Early Aspirin Use

The recommendation for early aspirin in acute ischemic stroke is supported by Grade 1A evidence from two landmark trials:

• International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST) combined data from 40,000 patients demonstrated that aspirin 160–300 mg within 48 hours reduced death or dependency, preventing 13 events per 1,000 treated. 1, 4, 3
• There was a highly significant reduction of 7 per 1,000 in recurrent ischemic stroke (1.6% aspirin vs. 2.3% control, P<0.000001) and a reduction of 4 per 1,000 in death without further stroke (5.0% vs. 5.4%, P=0.05). 3
• Against these benefits, there was an increase of 2 per 1,000 in hemorrhagic stroke (1.0% vs. 0.8%, P=0.07), yielding a net decrease of 9 per 1,000 in the overall risk of further stroke or death. 3

Special Considerations for Malignant Infarct

• Malignant cerebral infarction refers to large hemispheric strokes with significant mass effect and risk of herniation, typically involving the middle cerebral artery territory. 2
• Brain imaging is mandatory to exclude intracranial hemorrhage or hemorrhagic transformation before initiating aspirin therapy. 2
• For patients with severe renal impairment (CrCl < 30 mL/min), use aspirin monotherapy only (loading 160–325 mg, then 75–100 mg daily); clopidogrel is contraindicated due to metabolite accumulation and heightened bleeding risk. 4

Long-Term Management

• Continue aspirin 75–100 mg daily indefinitely for secondary stroke prevention after the acute phase. 1, 4, 2
• If a cardioembolic source (e.g., atrial fibrillation) is identified, transition to oral anticoagulation rather than antiplatelet therapy. 1