When can antiplatelet therapy (e.g. aspirin or clopidogrel) be resumed in a patient with a cerebral infarct (stroke) who has been treated with alteplase (tissue plasminogen activator, tPA)?

Antiplatelet Resumption After Alteplase in Acute Ischemic Stroke

Antiplatelet therapy should be started 24 hours after alteplase administration, following a follow-up CT or MRI scan to exclude hemorrhagic transformation. 1

Standard Protocol for Antiplatelet Resumption

The American Heart Association/American Stroke Association guidelines establish a clear timeline:

• Obtain neuroimaging at 24 hours post-alteplase (CT or MRI scan) before initiating any antiplatelet or anticoagulant therapy 1
• Start antiplatelet therapy after 24 hours if imaging excludes intracranial hemorrhage 1
• Avoid antiplatelet therapy within the first 24 hours as standard practice to minimize bleeding risk 1

This 24-hour waiting period is based on the pharmacodynamics of alteplase and the peak risk window for symptomatic intracranial hemorrhage, which occurs within the first 24-36 hours post-thrombolysis. 1

Evidence Against Early Antiplatelet Administration

The risk of early antiplatelet therapy (<24 hours) outweighs potential benefits:

• A randomized controlled trial (ARTIS trial) demonstrated that intravenous aspirin 300 mg given within 90 minutes of alteplase significantly increased symptomatic intracranial hemorrhage (4.3% vs 1.6%, p=0.04) without improving functional outcomes at 3 months 2
• Symptomatic intracranial hemorrhage was more often the cause of poor outcomes in the early aspirin group compared to standard treatment (11 vs 1 patients, p=0.006) 2
• The trial was terminated prematurely due to excess bleeding with no evidence of benefit 2

Uncertain Clinical Scenarios

When concomitant high-risk conditions exist (e.g., acute coronary syndrome, recent coronary stent), the decision becomes more nuanced:

• The 2018 AHA/ASA guidelines state that early antithrombotic use (<24 hours) "might be considered" only when withholding treatment poses substantial risk from the concomitant condition (Class IIb, Level B-NR) 1
• A retrospective Korean study found no increased hemorrhage risk with early antiplatelet initiation, but this was subject to selection bias and requires individualized risk-benefit assessment 1
• More recent retrospective data (2022) in patients receiving alteplase alone showed no increased symptomatic intracranial hemorrhage with early antiplatelet therapy, but this requires prospective validation 3

These scenarios remain exceptions, not the rule—the default remains waiting 24 hours.

Monitoring Requirements During the 24-Hour Window

Critical monitoring parameters before antiplatelet initiation: 1

• Blood pressure control: Maintain BP <180/105 mm Hg for at least 24 hours post-alteplase 1
• Neurological assessments: Every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 1
• Emergency imaging: Obtain immediate CT if patient develops severe headache, acute hypertension, nausea, vomiting, or neurological worsening 1

Choice of Antiplatelet Agent After 24 Hours

For most patients with acute ischemic stroke:

• Aspirin monotherapy (81-325 mg daily) is the standard choice for long-term secondary prevention after the 24-hour window 1
• Dual antiplatelet therapy (aspirin + clopidogrel) is only indicated for minor stroke (NIHSS ≤3) or high-risk TIA, and must be initiated within 24-72 hours of symptom onset to provide benefit 4, 5
• DAPT is contraindicated in moderate-to-severe stroke (NIHSS >3) at any timepoint, including after alteplase 4

Common Pitfalls to Avoid

• Do not start antiplatelet therapy before 24 hours based on perceived urgency—the bleeding risk is real and documented 2
• Do not skip the 24-hour imaging—hemorrhagic transformation may be clinically silent 1
• Do not initiate DAPT after 2 weeks post-stroke—the therapeutic window for DAPT benefit closes within 21-30 days, and late initiation provides no benefit over monotherapy 4
• Do not use DAPT in large vessel strokes—these typically have NIHSS >3, making them ineligible regardless of timing 4