Should antiplatelet regimen be loaded before thrombolysis in ischemic stroke?

Do NOT Load Antiplatelet Therapy Before Thrombolysis in Acute Ischemic Stroke

Antiplatelet agents must be withheld until 24 hours after thrombolysis and after post-treatment imaging has excluded intracranial hemorrhage. This is a critical safety measure to minimize bleeding risk, particularly symptomatic intracerebral hemorrhage (SICH).

Timing Algorithm for Antiplatelet Therapy in Acute Ischemic Stroke

For Patients Receiving IV tPA (Thrombolysis):

Step 1: Withhold all antiplatelets before and during thrombolysis 1

Step 2: Perform 24-hour post-thrombolysis brain imaging 1

Step 3: If imaging excludes intracranial hemorrhage, initiate aspirin 160-325 mg 1

Step 4: Continue aspirin 81-325 mg daily or transition to alternative antiplatelet regimen 1

For Patients NOT Receiving Thrombolysis:

Immediate aspirin loading (160-325 mg) is recommended within 48 hours of symptom onset after brain imaging excludes hemorrhage 1

Evidence Supporting Delayed Antiplatelet Therapy After Thrombolysis

The Canadian Stroke Best Practice Recommendations explicitly state that in clinical trials for tPA, antithrombotic drugs (including aspirin) were avoided until after the 24-hour post-thrombolysis scan had excluded intracranial hemorrhage 1. This practice was established to minimize bleeding complications while preserving the benefits of thrombolysis.

The American College of Chest Physicians guidelines similarly recommend early aspirin therapy (160-325 mg within 48 hours) for acute ischemic stroke, but this recommendation applies to patients not receiving thrombolysis 1. The distinction is critical: aspirin should be given early in non-thrombolyzed patients but delayed in those receiving IV tPA.

Bleeding Risk with Pre-Thrombolysis Antiplatelet Use

Patients already on antiplatelet therapy at the time of stroke who then receive thrombolysis face increased bleeding risk 2. Analysis of 11,865 patients in the SITS-ISTR registry revealed:

• Aspirin monotherapy at baseline: 2.5% SICH rate (vs 1.1% in antiplatelet-naïve patients) 2
• Dual antiplatelet therapy (aspirin + clopidogrel) at baseline: 4.1% SICH rate per SITS-MOST criteria and 13.4% per ECASS II criteria 2
• The combination of aspirin and clopidogrel was associated with a 2.11-fold increased risk of SICH (95% CI: 1.29-3.45) 2

While pre-existing antiplatelet use is not an absolute contraindication to thrombolysis, it underscores why loading antiplatelets immediately before thrombolysis would be contraindicated 2.

Role of Dual Antiplatelet Therapy (DAPT) - But NOT Before Thrombolysis

DAPT with aspirin plus clopidogrel is highly effective for minor stroke and high-risk TIA, but timing is crucial 3:

• Loading dose: Aspirin 160-325 mg + clopidogrel 300-600 mg 3
• Maintenance: Aspirin 81 mg + clopidogrel 75 mg daily for 21 days 3
• Initiation window: Within 12-24 hours of symptom onset 3
• Critical prerequisite: Intracranial hemorrhage must be excluded on neuroimaging 3

However, this DAPT regimen is indicated for patients with minor stroke or high-risk TIA who are NOT receiving thrombolysis, or it should be initiated after the 24-hour post-thrombolysis safety window 3, 4.

Common Pitfalls to Avoid

Pitfall #1: Giving aspirin immediately before or with thrombolysis to "maximize benefit" - this increases bleeding risk without proven benefit 1, 2

Pitfall #2: Assuming that because early aspirin is beneficial in non-thrombolyzed patients, it should also be given to thrombolyzed patients - the bleeding risk profile is completely different 1

Pitfall #3: Loading dual antiplatelet therapy in patients eligible for thrombolysis - this substantially increases SICH risk and should be avoided 2

Clinical Decision Framework

Acute Ischemic Stroke Patient Presents
↓
Is patient eligible for IV tPA within 4.5 hours?
↓
YES → Administer tPA WITHOUT antiplatelets
      ↓
      Wait 24 hours + obtain post-tPA brain imaging
      ↓
      No hemorrhage? → Start aspirin 160-325 mg
      
NO → Immediate aspirin 160-325 mg after imaging excludes hemorrhage
     ↓
     Consider DAPT if minor stroke (NIHSS ≤3) or high-risk TIA

The evidence is unequivocal: antiplatelet loading before thrombolysis is not supported by guidelines and increases bleeding risk without demonstrated benefit 1, 2.