Risk of Thrombolysis for Stroke After Pretreatment with Aspirin 300 mg
Prior aspirin use at 300 mg does not contraindicate IV thrombolysis for acute ischemic stroke, but administering aspirin concurrently with or immediately after thrombolysis significantly increases symptomatic intracranial hemorrhage risk and should be avoided for at least 24 hours post-thrombolysis. 1, 2
Key Guideline Recommendations
For IV Thrombolysis (Alteplase)
- Aspirin should be delayed until 24 hours after IV alteplase administration to minimize bleeding complications 1, 3
- The only exception is when concomitant conditions provide substantial benefit that outweighs the hemorrhage risk, though this requires careful individual assessment 1
- After the 24-hour delay, aspirin 160-300 mg should be initiated for secondary stroke prevention 1, 4
Evidence of Harm with Early Aspirin
The most definitive evidence comes from a 2012 randomized controlled trial that directly tested this question 2:
- Administering 300 mg IV aspirin within 90 minutes of alteplase increased symptomatic intracranial hemorrhage from 1.6% to 4.3% (absolute increase of 2.8%, p=0.04) 2
- This hemorrhage increase directly caused poor outcomes in 11 patients in the aspirin group versus only 1 in the standard treatment group (p=0.006) 2
- No benefit in functional outcomes was observed at 3 months (54.0% vs 57.2% favorable outcomes, p=0.42) 2
- The trial was terminated prematurely due to excess bleeding without evidence of benefit 2
For Mechanical Thrombectomy
The risk-benefit calculation differs for mechanical thrombectomy compared to IV thrombolysis:
- Aspirin 300 mg given as standard acute stroke treatment (within 24-48 hours of onset) is NOT a contraindication for mechanical thrombectomy 4, 3
- This reflects different pathophysiology and timing considerations than IV thrombolysis 3
- Most thrombectomy trials enrolled patients who received aspirin according to standard protocols 1
Clinical Algorithm for Aspirin Timing
If Patient Has NOT Received Thrombolysis:
- Start aspirin 160-300 mg within 24-48 hours of stroke onset 1, 4
- This provides small but significant reductions in mortality (9 fewer deaths per 1,000) and improved functional outcomes (7 more good outcomes per 1,000) 1
If Patient WILL Receive IV Thrombolysis:
- Hold all antiplatelet agents until 24 hours post-thrombolysis 1, 3
- Obtain follow-up brain imaging at 24 hours to exclude intracranial hemorrhage before starting aspirin 3
- Then initiate aspirin 160-300 mg for secondary prevention 1
If Patient Received Thrombolysis and Needs Urgent Antiplatelet Therapy:
- Recent data suggest low-dose aspirin (81 mg) at 18-21 hours post-thrombolysis may be safe, with only 1 bleeding event in 50 patients 5
- However, this remains off-guideline and should only be considered when compelling indications exist (e.g., acute coronary syndrome) 1
- The standard 24-hour delay remains the safest approach 1, 2
Historical Context and Older Guidelines
Earlier guidelines from 2003 noted that combining aspirin with thrombolytic agents (streptokinase) resulted in "unacceptably high incidence of early mortality and intracranial hemorrhage" 1. While this involved streptokinase rather than alteplase, the principle of avoiding concurrent antiplatelet therapy with thrombolysis has remained consistent 1.
The International Stroke Trial and Chinese Acute Stroke Trial established aspirin's benefit in acute stroke but specifically excluded patients receiving thrombolysis, demonstrating a 0.1% absolute increase in intracranial hemorrhage even without thrombolysis 1.
Common Pitfalls to Avoid
- Do not reflexively give aspirin in the emergency department before determining thrombolysis eligibility - this creates an unnecessary 24-hour delay in definitive treatment 1
- Do not use aspirin as a substitute for thrombolysis or thrombectomy in otherwise eligible patients (Class III recommendation) 1, 4
- Do not combine aspirin with clopidogrel acutely unless the stroke is minor (NIHSS ≤3), as dual antiplatelet therapy increases bleeding risk 6, 7