Acute Aspirin Therapy

All acute stroke patients not already on an antiplatelet agent should be given at least 160 mg of acetylsalicylic acid (ASA) immediately as a one time loading dose after brain imaging has excluded intracranial hemorrhage [Evidence Level A].

In patients treated with recombinant tissue plasminogen activator (r-tPA), acetylsalicylic acid (ASA) should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage [Evidence Level B].
Acetylsalicylic acid (80 to 325 mg daily) should then be continued indefinitely or until an alternative antithrombotic regime is started [Evidence Level A].
Refer to recommendations 2.5 and 2.6 for additional information.
In dysphagic patients, acetylsalicylic acid may be given by enteral tube or by rectal suppository [Evidence Level A].
In paediatric patients, initial treatment with low molecular weight heparin should be considered and continued until cervical artery dissection and intracardiac thrombus is excluded. If neither is present, switch to acute aspirin therapy at dose of 1-5 mg/kg [Evidence Level B].
In patients already on acetylsalicylic acid prior to ischemic stroke or transient ischemic attack, clopidigrel may be considered as an alternative [Evidence Level B]. If rapid action is required then a loading dose of 300 mg of clopidigrel could be considered, followed by a maintenance dose of 75 mg once a day.

Rationale

Acute-phase aspirin therapy reduces the risk of early recurrent ischemic stroke. Long-term aspirin therapy reduces the risk of ischemic stroke, myocardial infarction, and vascular death. There are no data from randomized controlled trials to support the use of other antiplatelet regimes in acute stroke patients. In the National Institute of Neurological Disorders and Stroke r-tPA Stroke Study, antithrombotic drugs (including aspirin) were avoided until after the 24-hour post-thrombolysis scan had excluded intracranial hemorrhage. Aspirin therapy also reduces the risk of venous thromboembolism.

System Implications

Protocols and standing order sets should be developed and available to guide initial management of ischemic stroke and transient ischemic attack patients.

Performance Measures

Proportion of ischemic stroke patients who receive acute aspirin therapy within the first 48 hours following a stroke event (core).
Median time from stroke onset to administration of first dose of aspirin in hospital.

Measurement Notes

Time interval measurements should be taken from the time the patient is triaged or registered at the hospital (whichever time comes first) until the time the first dose is administered.
This indicator focuses on aspirin. Some centres may include other antiplatelet medications, such as clopidogrel, ticlopidine, or ASA combined with extended release dipyridamole. In cases where another agent is used instead of aspirin in the first 48 hours, this should be noted in the indicator definition.
Possible data sources include history and physical, physician’s admission notes, nurses’admission notes, medication record.

Summary of the Evidence

The 2008 update of the Cochrane systematic review of aspirin in acute stroke included twelve trials involving 43,041 patients.²⁴² Two trials testing aspirin 160 to 300 mg once daily started within 48 hours of onset contributed 94 percent of the data. The maximum follow-up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow up (odds ratio 0.95, 95% confidence interval 0.91 to 0.99). For every 1000 patients treated with aspirin, 13 patients will avoid death or dependency (number needed to treat to benefit: 79). Antiplatelet therapy was associated with a small but definite excess of symptomatic intracranial hemorrhages, but this was more than offset by the reduction of recurrent ischemic strokes and pulmonary embolus. The authors concluded antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in patients who cannot swallow), and started within 48 hours of onset of presumed ischemic stroke reduces the risk of early recurrent ischemic stroke without a major risk of early hemorrhagic complications and improves long-term outcome.

Several international stroke guidelines referenced in this document state that patients treated with tPA should not receive any antiplatelet or anticoagulant therapy for the first 24 hours after beginning treatment.

Long-term antiplatelet therapy reduces the risk of subsequent serious vascular events by about one quarter.²⁴³ In-hospital initiation of secondary prevention therapy before hospital discharge after an ischemic stroke or transient ischemic attack is associated with high treatment adherence rates three months after hospitalization.²⁴⁴

Due to the lack of high-quality, randomized controlled trials in the literature, controversy exists in the discussion of hyperacute management of paediatric stroke patients. The Royal College of Physicians and the American Heart Association paediatric stroke guidelines discussed using low molecular weight heparin if there is a known dissection or cardiac clot, and otherwise using ASA.^{41, 12} The American College of Chest Physicians guidelines discuss starting low molecular weight heparin initially, assuming dissection or cardiac clot may be present until proven otherwise.⁴⁴

Although the paediatric research is just emerging, it is clear that transient ischemic attack/ stroke recurrence rate in children with arterial ischemic stroke is nearly 50 percent without antithrombotic treatment, demonstrating that paediatric stroke must be promptly diagnosed and treated.¹³⁸ Data from the Warfarin-Aspirin Recurrent Stroke Study Trial in the adult sub-groups most similar to children with stroke (i.e. non-hypertensive, non-atherosclerotic) show benefit to anticoagulation over aspirin in preventing recurrent stroke.²¹⁹

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