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Section 3.5

Acute Aspirin Therapy *NEW!

4th Edition
2012-2013 UPDATE
May 23, 2013

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].

  1. In patients treated with tissue plasminogen activator (tPA), acetylsalicylic acid (ASA) should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage [Evidence Level B].
  2. 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.
  3. In dysphagic patients, acetylsalicylic acid may be given by enteral tube or by rectal suppository [Evidence Level A].
  4. In pediatric patients, initial treatment with anticoagulation (heparin) or aspirin at established pediatric dosing 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]. (Roach et al 2008)
  5. 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 [Evidence Level B].
    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 is a paucity of data from randomized controlled trials to support the use of other antiplatelet regimes in acute stroke patients. In clinical trials for tPA, antithrombotic drugs (including aspirin) were avoided until after the 24-hour post-thrombolysis scan had excluded intracranial hemorrhage.

    System Implications
    • Protocols and standing order sets should be developed and available to guide initial management of ischemic stroke and transient ischemic attack patients
    • Pediatric awareness campaigns and education to healthcare professionals to optimize recognition of stroke and management.
    Performance Measures
    1. Proportion of ischemic stroke or TIA patients who receive acute aspirin therapy within the first 48 hours following symptom onset (core).
    2. 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 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

    In an updated Cochrane review, Sandercock and colleagues identified 12 RCTs (n=43,041) comparing placebo/no treatment to antiplatelet therapy initiated within 14-days of the onset of ischemic stroke (Sandercock, Counsell, Gubitz, & Tseng, 2009). Two large trials investigating aspirin therapy (160-300 mg/day) initiated within 48-hours of stroke onset contributed 94% of the data. Treatment with aspirin was associated with a significant decrease in death or dependency at follow up (at least one-month post-stroke; OR=0.95, 95% CI 0.91 to 0.99). Moreover, the authors reported that for every 1000 patients treated with aspirin, 13 will avoid death or dependency (number needed to treat to benefit = 79). Although antiplatelet therapy was associated with a significant increase in the odds of intercerebral hemorrhage (OR=1.33, 95% CI 1.10 to 1.62), a net reduction was reported in terms of the odds of any stroke recurrence (i.e., ischemic or hemorrhagic; OR=0.88, 95% CI 0.80 to 0.97). Sandercock et al. concluded that aspirin therapy initiated within 48 hours of ischemic stroke improves long-term outcomes without producing a major risk of early hemorrhagic complication (Sandercock et al., 2009).

    Current evidence suggests that patients should not receive antiplatelet therapy within 24-hours of treatment with tPA due to increased risk of symptomatic intercrainial hemorrhage (Zinkstok & Roos, 2012). Evidence also suggests that long-term antiplatelet therapy reduces the risk of subsequent serious vascular events by about one quarter (Sandercock et al., 2009). In-hospital initiation of secondary prevention therapy after an ischemic stroke or transient ischemic attack is associated with greater adherence rates three-months following discharge (Ovbiagele et al., 2004).

    Due to a lack of high-quality, randomized controlled trials in the literature, controversy exists regarding the use of antiplatelets in the hyperacute management of paediatric stroke patients. The Royal College of Physicians and the American Heart Association paediatric stroke guidelines both recommend the use of aspirin unless there is a known dissection or cardiac clot, in which case low molecular weight heparin is recommend (Paediatric Stroke Working Group, 2004; Roach et al., 2008). Conversely, the American College of Chest Physicians guidelines recommend that low molecular weight heparin should be used until the absence of dissection or cardiac clot is established (Guyatt, Cook, Jaeschke, Pauker, & Schunemann, 2008). Although the current paediatric literature base is limited, it is clear that the rate of transient ischemic attack / stroke recurrence in children with arterial ischemic stroke is nearly 50% without antithrombotic treatment, demonstrating the need for prompt diagnosis and treatment within paediatric stroke patients (Antithrombotic Trialists' Collaboration, 2002). Results from the Warfarin-Aspirin Recurrent Stroke Study Trial, in a sub-group analysis of adults who are somewhat similar to children with stroke (i.e. non-hypertensive, non-atherosclerotic), reveal a benefit of anticoagulation over aspirin in preventing stroke recurrence (Fullerton, Wu, Sidney, & Johnston, 2007).

    Evidence Table 3.5 and References