Antiplatelet Initiation After IV Alteplase or Mechanical Thrombectomy in Stroke
Primary Recommendation
Aspirin should be initiated 24 hours after IV alteplase administration, not earlier, as early administration increases symptomatic intracranial hemorrhage without improving outcomes. 1 For patients who undergo mechanical thrombectomy without alteplase, aspirin can be started within 24-48 hours of stroke onset. 1
Standard Protocol After IV Alteplase
Timing of Aspirin Initiation
Delay aspirin for 24 hours after IV alteplase in the vast majority of patients, as this is the evidence-based standard supported by the 2018 AHA/ASA guidelines (Class I, Level A). 1
The recommended dose is 160-325 mg when initiated, based on the large clinical trials (IST and CAST) that established aspirin's benefit in acute stroke. 1
Aspirin should not be used as a substitute for alteplase or mechanical thrombectomy in otherwise eligible patients (Class III: No Benefit). 1
Evidence Against Early Administration
A 2012 randomized controlled trial (ARTIS trial) demonstrated that intravenous aspirin 300 mg given within 90 minutes of alteplase increased symptomatic intracranial hemorrhage from 1.6% to 4.3% (p=0.04) without improving 3-month outcomes. 2
A 2021 meta-analysis confirmed that early antiplatelet therapy after alteplase provides no efficacy benefit (95% CI 0.97-1.32) and has a neutral-to-harmful effect on hemorrhage risk. 3
The 2018 AHA/ASA guidelines explicitly state that the risk of antithrombotic therapy within 24 hours after alteplase (with or without mechanical thrombectomy) is uncertain (Class IIb, Level B-NR). 1
Exception: High-Risk Comorbid Conditions
Antiplatelet therapy within 24 hours might be considered only when there is a concomitant condition where withholding treatment poses substantial risk or where treatment provides substantial benefit independent of the stroke. 1
Examples include:
- Acute coronary syndrome requiring immediate antiplatelet therapy 1
- Recent coronary stent placement where dual antiplatelet interruption carries high thrombotic risk 1
- Mechanical thrombectomy requiring acute stent placement for intracranial atherosclerotic disease 4
Evidence for Selective Early Use
A 2020 case series of 6 patients who received antiplatelets within 4.9 hours (median) of tPA due to intracranial stent placement during mechanical thrombectomy showed no symptomatic intracranial hemorrhage, though this was highly selected and underpowered. 4
A retrospective Korean study found no increased hemorrhage risk with early antiplatelet initiation after alteplase or mechanical thrombectomy, but this was subject to selection bias and the 2018 AHA/ASA guidelines emphasize individualized risk-benefit assessment. 1
Protocol After Mechanical Thrombectomy Alone (No Alteplase)
Standard Approach
For patients who undergo mechanical thrombectomy without receiving IV alteplase, aspirin should be initiated within 24-48 hours of stroke onset following the same evidence base as non-thrombolyzed stroke patients (Class I, Level A). 1
The 2012 ACCP guidelines recommend early aspirin therapy (within 48 hours) at 160-325 mg for acute ischemic stroke patients not receiving thrombolysis (Grade 1A). 1
Special Consideration: Intraprocedural Stenting
When mechanical thrombectomy requires intracranial stent placement (for underlying atherosclerotic disease or dissection), immediate antiplatelet loading may be necessary despite theoretical hemorrhage risk. 4
This scenario requires balancing acute stent thrombosis risk against hemorrhagic transformation risk, with no high-quality evidence to guide timing. 4
Minor Stroke and Dual Antiplatelet Therapy
For patients with minor stroke (NIHSS ≤3) or high-risk TIA who did NOT receive alteplase, dual antiplatelet therapy (aspirin plus clopidogrel) initiated within 24 hours and continued for 21 days can be beneficial for early secondary stroke prevention (Class IIa, Level B-R). 1
This recommendation is based on the CHANCE and POINT trials showing reduced 90-day stroke recurrence with DAPT in minor stroke/TIA. 1
However, a 2021 meta-analysis confirmed that DAPT reduces recurrent stroke (RR 0.76,95% CI 0.68-0.83) but increases major bleeding (RR 2.22,95% CI 1.14-4.34). 5
This DAPT recommendation does NOT apply to patients who received alteplase, where the 24-hour delay for any antiplatelet remains standard. 1
Critical Pitfalls to Avoid
Never administer aspirin or other antiplatelets within 24 hours of IV alteplase in routine practice, as this increases symptomatic intracranial hemorrhage without benefit. 2, 3
Do not delay mechanical thrombectomy evaluation or transfer to observe aspirin response, as aspirin is not a substitute for reperfusion therapy and any delay worsens outcomes. 1, 6
Do not withhold aspirin beyond 24-48 hours post-stroke in patients who did not receive alteplase, as early aspirin (within 48 hours) reduces recurrent stroke and is strongly recommended (Grade 1A). 1
Do not use glycoprotein IIb/IIIa inhibitors (abciximab) in acute stroke, as they are potentially harmful (Class III: Harm). 1