Time to antithrombotic therapy after transient ischaemic attack and ischaemic stroke

Aspirin and other antithrombotics are proven to be effective in reducing ischaemic stroke recurrence

Reperfusion therapy (mechanical thrombectomy or thrombolytic therapy) is highly effective and improves outcomes for appropriately selected patients presenting with ischaemic stroke to a comprehensive stroke centre. Unfortunately, the majority of such patients are not eligible for reperfusion therapy; however, patients with ischaemic stroke benefit from other aspects of stroke unit care, and this includes early antiplatelet therapy such as aspirin.1^,2 Even though the number needed to treat (NNT) with aspirin to prevent recurrent ischaemic stroke is high, the drug cost is low and most patients are eligible.3 A meta‐analysis of trials evaluating early use of aspirin after transient ischaemic attack (TIA) or ischaemic stroke showed that the effect of aspirin on recurrence was significant by the second day of starting aspirin (hazard ratio [HR], 0.44; 95% CI, 0.25–0.76; P<0.0034), and the NNT to prevent stroke on day 2 was 637 (95% CI, 475–1488).4 Among patients given aspirin before randomisation, the effect was seen within 24 hours (HR, 0.31; 95% CI, 0.11–0.85; P = 0.020). The effect of aspirin was greatest for mild (odds ratio [OR], 0.51 [95% CI, 0.34–0.75]; NNT, 118 [95% CI, 88–233]), followed by moderate (OR, 0.65 [95% CI, 0.44–0.98]; NNT, 123 [95% CI, 82–2318]) and severe ischaemic stroke (OR, 1.10; 95% CI 0.77–1.58).4 The importance of early antiplatelet therapy was reaffirmed by subsequent trials that enrolled patients with high risk TIA and mild to moderate ischaemic stroke within 24 hours and used combinations of aspirin and clopidogrel5 or aspirin and ticagrelor.6 Used early, these combination strategies had a similar impact on stroke recurrence.

Despite this, antiplatelet therapy is not always administered early; we will explore the possible hospital barriers to these therapies and discuss potential areas of improvement as well as the findings from recent antiplatelet trials.

Hospital barriers

The focus on dysphagia screening is due to the concern that aspiration may lead to stroke‐associated pneumonia.7 This has resulted in dysphagia screening becoming a standard key performance indicator in patients, even in those with very low risk of pneumonia, such as patients with TIA and minor ischaemic stroke.8 This emphasis on dysphagia screening can adversely delay patient access to preventive antiplatelet treatment. In an audit at our institution,8 we showed that the median time from triage to antithrombotic administration was 15.1 hours (interquartile range, 5.5–27.2 hours). The proportion of patients receiving antithrombotics was 41.7% (n = 219) at 12 hours, 65.1% at 24 hours (n = 342) and 86.5% at 48 hours (n = 454). Patients who were given alteplase received delayed antiplatelet therapy at 24 hours but were similar to the group who did not receive alteplase by 48 hours.8 Other clues to the competing clinical care priorities of performing dysphagia screening and administering timely antiplatelet therapy come from rapid TIA programs, where the aim is to discharge patients directly from the emergency department. These programs achieve high frequency of early aspirin use (92.2%).9 By contrast, the percentage of patients with TIA who were admitted to hospital and received antithrombotic therapy within 24 hours was 80.9% (n = 34), with 90.5% (n = 38) receiving this therapy at 48 hours.10 Among these admitted patients with TIA, 38.1% (n = 16) were kept nil by mouth. It is not clear if a dysphagia screen is necessary in patients with TIA as by definition they have had resolution of their neurological deficits and would hence appear to have very low risk of aspiration (0 of 42 patients).8

Similar to the experiences with TIA, patients with minor ischaemic stroke (National Institute of Health Stroke Scale [NIHSS]<5) are also kept nil by mouth in 57.4% (27 of 47) of cases. Interestingly, the single patient (one in 47) who developed pneumonia in our study had passed a dysphagia screen on admission before developing pneumonia on day 3 after the stroke.10 The issue of dysphagia screening and antiplatelet administration may reflect different practices across the world. In a North American trial comparing oral aspirin and intravenous alteplase in patients with minor stroke,11 39% of the patients had facial palsy and 28% had dysarthria.11 These patients would have failed the Acute Screening of Swallow in Stroke/TIA (ASSIST) tool used in Victoria, Australia, as it includes facial palsy as one of the items to indicate if the patient requires further evaluation by a speech therapist. Due to limited resources, it is unlikely that speech therapists can be available around the clock to assess a patient who has failed a dysphagia screen. It is more likely that the speech therapy assessment will occur later in the morning and aspirin administration may then be delayed to the following day.

Lessons from the North American program

In North America, hospitals must meet a minimal threshold of 85% for antithrombotic administration within 48 hours in order to join the Get With the Guidelines (GWTG) stroke program. Using their performance improvement program, they have demonstrated an increase in antithrombotic administration within 48 hours from 91.5% to 97.0% over 5years.12 Among primary stroke centres in North Carolina, the frequency of dysphagia screening was 67.7% and the percentage of patients who had antithrombotics administered within 48 hours was 94.5%.13 A feature notable in North America is that the dysphagia screen is considered to have strength/class of recommendation IIa (moderate benefit to risk ratio) but level of evidence C‐LD (limited data).2 A meta‐analysis of randomised trials concluded that there’s insufficient evidence to conclude about the effect of dysphagia screening on reducing the risk of pneumonia and further trials are needed.14 By contrast, the Stroke Foundation living guidelines recommend that a dysphagia screen should be performed after stroke, with the practice statement listed as consensus‐based.1 Despite this, the dysphagia screen is now a standard part of early evaluation of patients with stroke in Australia. The positive relationship between post‐stroke pneumonia and stroke severity provides an opportunity for selected approach to dysphagia screen.8 Rather than considering that all patients with stroke and TIA are the same, resources should be diverted to patients who are at higher risk of pneumonia and thus reduce the requirement for dysphagia screen in all patients that can potentially delay oral antiplatelet administration.

Lessons from our recent experience

We have found that the time to antithrombotic treatment can be reduced when antithrombotics are prescribed as a “stat” (to be given immediately) order, in addition to prescribing on routine chart. An issue with prescribing on the routine chart alone is that the medications will not be given until the time that the drug is charted. In the case of aspirin, this is often charted as 8am and thus will not be given until the routine medication round the next day. Prescribing using a stat order will get around this issue, but the stat order approach alone is not sufficient, as we also found aspirin and other antithrombotics were not given in 13.9% of cases.8 Strategies to deal with these issues cannot be implemented without a hypervigilant stroke unit working together to check on timely administration of aspirin. By this we mean that the responsibility for stroke prevention lies within the entire team. It is likely that an implementation style approach is required, with both top‐down (policy and supported by hospital executives) and bottom‐up (dedicated workshop, vigilance at handover and ward round, or reminders in electronic medical record software) procedures.

An example to discuss in a workshop setting might be how to troubleshoot a situation in which the team prescribed aspirin at 9am but the hospital routine is to give oral medication at 8am. This could also guide the team members around antiplatelet options available for patients who are kept nil by mouth and initiate internal unit discussion. There are three inexpensive options available: chewable aspirin (sublingual absorption and costs $0.15 per tablet), rectal aspirin (uncomfortable for patients and costs $5.30) or intravenous aspirin (costs $20.00 per dose).

Lessons from recent trials

Stroke teams also need to consider alternative approaches to evaluating safety to take oral medications. The investigators from a recent antiplatelet trial (aspirin and ticagrelor) successfully performed the trial in patients with moderate ischaemic stroke.6 They had empowered clinicians (doctors and nurses) to use a simple bedside water swallowing test to evaluate safety to take oral medications.15 One advantage of this test over ASSIST for assessing medication safety is that it is not weighted by facial weakness. The water sip test can also be used for patients who have recurrent ischaemic stroke while receiving aspirin. For patients who have ischaemic stroke in the setting of atrial fibrillation and deemed to require oral anticoagulation (dabigatran, apixaban or rivaroxaban) the above approach to evaluating safety for oral medications can potentially be used.

Myths

The 48‐hour window for commencement of aspirin has been used in trials from the 1990s, possibly due to difficulty in obtaining computed tomography scans at the time. Imaging delay is no longer a valid reason for delays in patients receiving aspirin, and recent trials with dual antiplatelet therapy have shown that the time window should be shortened to 24 hours.

In this article we have drawn attention to this neglected area and illustrate several strategies available to improve stroke/TIA patient care, as well as lessons from recent antithrombotic trials, such as the use of a bedside water swallow test. We need to change our work practice to recognise that time to aspirin and other antithrombotics are an important component of stroke unit care as they are proven to be effective in reducing ischaemic stroke recurrence. This is possible to achieve while avoiding complications of oral intake of medicines. It is time that we focus our attention on time to aspirin and other antithrombotic therapies.