When can aspirin (acetylsalicylic acid) and clopidogrel be continued after tenecteplase treatment for an acute ischemic stroke?

When to Continue Aspirin and Clopidogrel After Tenecteplase for Stroke

Delay all antiplatelet agents (both aspirin and clopidogrel) until 24 hours after tenecteplase administration, after a follow-up CT scan has excluded intracranial hemorrhage. 1

Timing Algorithm for Antiplatelet Initiation Post-Thrombolysis

Step 1: Mandatory 24-Hour Waiting Period

• Do not start any antiplatelet therapy until at least 24 hours after tenecteplase bolus 1
• Obtain a follow-up CT scan at 24 hours post-thrombolysis to rule out hemorrhagic transformation 1
• Only proceed with antiplatelet therapy if imaging confirms no intracranial hemorrhage 1

Step 2: Determine Stroke Severity and Eligibility for Dual Therapy

For Minor Stroke (NIHSS ≤3) or High-Risk TIA (ABCD² ≥4):

• After the 24-hour scan excludes hemorrhage, immediately initiate dual antiplatelet therapy (DAPT) with: 1, 2, 3
  • Clopidogrel 300-600 mg loading dose (300 mg acceptable, 600 mg used in POINT trial) 1, 2
  • Aspirin 160-325 mg loading dose 1, 2
• Continue maintenance dosing for exactly 21 days: 1, 3, 4
  • Clopidogrel 75 mg daily
  • Aspirin 75-100 mg daily
• After day 21, transition to single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) indefinitely 1, 3, 4

For Moderate-to-Severe Stroke (NIHSS >3):

• After the 24-hour scan excludes hemorrhage, start aspirin monotherapy only: 1
  • Aspirin 160-325 mg as single loading dose
  • Continue aspirin 81-325 mg daily indefinitely
• Do not use dual antiplatelet therapy in this population 1, 3

Critical Evidence Supporting the 24-Hour Delay

The Canadian Stroke Best Practice guidelines explicitly state that in patients treated with tissue plasminogen activator (which includes tenecteplase), antiplatelet agents should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 1. This recommendation carries Evidence Level B and is designed to minimize the risk of hemorrhagic transformation during the period of maximal thrombolytic effect 1.

Recent research suggests that low-dose aspirin (81 mg) administered at 18-21 hours post-thrombolysis may be safe, with only 1 hemorrhagic event in 130 patients and no statistical increase in bleeding compared to administration after 24 hours 5. However, current guideline consensus remains at the 24-hour threshold 1, and deviating earlier should only be considered in exceptional circumstances with documented absence of hemorrhage on earlier imaging.

Special Timing Considerations for DAPT

The benefit of dual antiplatelet therapy is highly time-dependent and confined to the first 21 days after stroke onset 6, 7. Pooled analysis of the CHANCE and POINT trials (10,051 patients) demonstrated that major ischemic events were reduced primarily within the first 21 days (HR 0.66,95% CI 0.56-0.77), but not from day 22 to day 90 6. This means the 24-hour delay for thrombolysis patients still leaves a therapeutic window of 20 days for DAPT benefit.

Common Pitfalls to Avoid

• Never start antiplatelet therapy before 24 hours post-tenecteplase without repeat imaging 1
• Never continue DAPT beyond 21-30 days as bleeding risk (HR 2.32 for major hemorrhage) outweighs benefit 1, 3, 8
• Never use DAPT in patients with NIHSS >3 as this population was not studied in CHANCE/POINT trials 1, 3
• Never substitute antiplatelet therapy for thrombolysis or thrombectomy in eligible patients 1, 2
• Never use enteric-coated aspirin for loading doses due to slower onset of action 2

Alternative Routes for Dysphagia

If the patient cannot swallow at 24 hours post-thrombolysis: 1

• Aspirin 80 mg daily via enteral tube, OR
• Aspirin 325 mg rectal suppository daily
• Clopidogrel 75 mg daily via enteral tube (after loading dose)