In a patient with a massive ischemic stroke, when is it safe to start antiplatelet therapy, what loading and maintenance doses of aspirin (or alternatives if aspirin‑intolerant) should be used, and what monitoring is required?

Starting Antiplatelet Therapy in Massive Ischemic Stroke (ASPECT 1)

In a patient with massive ischemic stroke (ASPECT score 1), aspirin 160–325 mg should be initiated within 24–48 hours after CT/MRI excludes intracranial hemorrhage, with the timing delayed to at least 24 hours post-thrombolysis if IV alteplase was administered; dual antiplatelet therapy is contraindicated in this setting due to the large infarct volume and high hemorrhagic transformation risk. 1, 2

Initial Assessment and Imaging Requirements

• Obtain urgent non-contrast CT or MRI before any antiplatelet agent is given to exclude intracranial hemorrhage. 1, 2
• Confirm ASPECT score and stroke severity using NIHSS; massive stroke typically presents with NIHSS > 15 and ASPECT ≤ 3. 1
• Assess swallowing function with a dysphagia screen before oral medication administration. 2

Timing of Antiplatelet Initiation

For Patients Who Did NOT Receive IV Thrombolysis

• Start aspirin 160–325 mg within 24–48 hours of symptom onset immediately after hemorrhage is excluded on imaging. 1, 2
• Maximum benefit occurs when aspirin is initiated within the first 24–48 hours; do not delay beyond 48 hours. 1, 3

For Patients Who Received IV Alteplase

• Delay aspirin administration until at least 24 hours after thrombolysis to minimize hemorrhagic risk. 1, 2
• Obtain repeat neuroimaging at 24 hours post-thrombolysis to confirm absence of hemorrhagic transformation before starting aspirin. 1

Loading and Maintenance Dosing Protocol

Loading Dose (Day 1)

• Aspirin 160–325 mg as a single loading dose (non-enteric coated formulation preferred for rapid absorption). 1, 2, 4
• For patients unable to swallow: aspirin 325 mg rectal suppository OR aspirin 81 mg via nasogastric/enteral tube. 1, 2
• Avoid enteric-coated aspirin for the loading dose as it delays absorption when rapid platelet inhibition is needed. 1, 2

Maintenance Dose (Day 2 Onward)

• Aspirin 75–100 mg once daily starting on day 2 and continued indefinitely for secondary stroke prevention. 1, 2, 3

Why Dual Antiplatelet Therapy Is Contraindicated

• Dual antiplatelet therapy (aspirin + clopidogrel) is recommended ONLY for minor stroke (NIHSS ≤ 3) or high-risk TIA (ABCD² ≥ 4). 1, 5
• In massive stroke with ASPECT score 1, the large infarct volume creates prohibitive hemorrhagic transformation risk that outweighs any potential benefit from dual therapy. 1, 5
• The CHANCE and POINT trials that established dual therapy efficacy explicitly excluded moderate-to-severe strokes (NIHSS > 3–5). 1, 6

Absolute Contraindications to Aspirin

• Intracranial hemorrhage not excluded on neuroimaging 1, 2
• Active major bleeding (e.g., gastrointestinal hemorrhage) 1, 7
• Severe thrombocytopenia 1
• Known aspirin hypersensitivity or documented aspirin allergy 2, 7
• IV alteplase administered within the preceding 24 hours 1, 2

Monitoring Requirements

First 24–72 Hours

• Monitor neurological status with serial NIHSS assessments every 4–6 hours to detect early deterioration or hemorrhagic transformation. 1
• Obtain repeat CT/MRI at 24 hours if clinical deterioration occurs or routinely after thrombolysis before starting aspirin. 1
• Monitor for signs of bleeding: hematemesis, melena, hematuria, unexplained drop in hemoglobin, or new neurological deficits. 7

Ongoing Monitoring

• Check complete blood count if bleeding is suspected or at baseline if prolonged hospitalization. 7
• Monitor blood pressure closely; maintain systolic BP < 180 mmHg to reduce hemorrhagic transformation risk in large infarcts. 1
• No routine platelet function testing is required for aspirin monotherapy. 1

Special Populations and Considerations

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. 1, 7

Dysphagia or Impaired Swallowing

• Aspirin 325 mg rectal suppository daily OR aspirin 81 mg via nasogastric/enteral tube (non-enteric coated). 1, 2

Planned Decompressive Hemicraniectomy

• Discuss antiplatelet strategy with neurosurgery; aspirin may need to be held 5–7 days before surgery if hemorrhagic risk is deemed excessive. 7
• Balance surgical bleeding risk against thrombotic risk; in massive stroke with planned early surgery, aspirin may be deferred until post-operative period. 1

Critical Pitfalls to Avoid

• Never use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible patients; this delays definitive reperfusion and worsens outcomes. 1, 2
• Never initiate dual antiplatelet therapy in massive stroke (NIHSS > 5 or ASPECT ≤ 3); the hemorrhagic risk is prohibitive. 1, 5
• Never delay aspirin beyond 48 hours when eligibility criteria are met; time-dependent benefit is lost. 1, 3
• Never use glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) in acute ischemic stroke; they are potentially harmful. 1
• Never use ticagrelor instead of aspirin in acute stroke; no proven benefit and higher bleeding risk. 1

Evidence Supporting Early Aspirin in Massive Stroke

• The International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST) enrolled over 40,000 patients and demonstrated that aspirin 160–300 mg within 48 hours reduces death or dependency, preventing 13 events per 1,000 treated (NNT 79). 1, 4, 3
• These trials showed a reduction of 7 per 1,000 in recurrent ischemic stroke and a net decrease of 9 per 1,000 in overall stroke or death, despite a small increase (2 per 1,000) in hemorrhagic stroke. 1, 3
• Grade 1A evidence (highest quality) supports aspirin monotherapy in acute ischemic stroke of all severities when hemorrhage is excluded. 1, 3

Long-Term Secondary Prevention

• Continue aspirin 75–100 mg daily indefinitely after the acute phase. 1, 2, 3
• If a cardioembolic source (e.g., atrial fibrillation) is identified during workup, transition to oral anticoagulation rather than continuing antiplatelet therapy. 1
• Clopidogrel 75 mg daily is an acceptable alternative for patients with aspirin intolerance, diabetes, or peripheral arterial disease. 1