Tableaux de données probantes et liste de référence
Patients who present with TIA or minor stroke are at increased risk of recurrent stroke, particularly within the first week following the initial event. A systematic review conducted by Giles & Rothwell (2007) pooled the results from 18 studies, consisting of 10,126 patients with TIA. The risk of stroke at days 2 and 7 was 3.1% 5.2%, respectively. More recently, Perry et al. (2014) examined stroke risk in 3,906 patients with TIAs admitted to 8 emergency departments over a 5-year period. In this cohort, 86 patients (2.2%) developed subsequent stroke within 7 days, and 132 (3.4%) at 90 days. Purroy et al. (2012) reported similar recurrent stroke in 2.6% of patients within 7 days and 3.9% within 90 days among 1,137 patients admitted to 30 centers in Spain, presenting with TIA. Following the first 30 days, the risk of recurrent stroke appears to decline. Mohan et al. (2011) included the results from 13 studies of patients recovering from first-ever stroke who were participants of hospital and community-based stroke registries. The cumulative risks of stroke recurrence: over time were 3.1% at 30 days; 11.1% at one year; 26.4% at 5 years; and 39.2% at 10 years. Callaly et al. (2016) followed 567 participants of the North Dublin Population Stroke Study. The reported cumulative incidence of stroke recurrence was 5.4% at 90 days, 8.5% at one year and 10.8% at 2 years with a 2-year case fatality of 38.6%. These findings highlight the value of assessing patients who present with suspected stroke or TIA according to time since onset of symptoms.
Several clinical scales, such as ABCD and ABCD2, have been developed for use by primary care and emergency department physicians to help guide triage decisions for patients presenting with possible TIA or minor stroke. While simple to apply, they may fail to identify patients with atrial fibrillation or significant carotid stenosis. The limitations of the ABCD2 score were recently highlighted in a meta-analysis including the results of 29 studies (Wardlaw et al. 2015). In a hypothetical cohort of 1,000 unselected clinic referrals, the poor specificity of the scale (35.4%) resulted in a large number of stroke mimics being identified as high risk (i.e., ABCD2 score ≥ 4). Rapid clinical assessment by stroke specialists and subsequent investigations to differentiate TIA and minor stroke from other potential causes are essential to ensure that secondary prevention strategies can be implemented as soon as possible. Urgent TIA clinics provide such a model of care. The TIAregistry.org project is a prospective registry designed to follow patients presenting with TIA or minor stroke over a 5-year period. Patients were included if the event had occurred within the previous 7 days. The preliminary one-year results, which included 4,583 patients recruited from 61 sites in 21 countries from 1997-2003, indicated that 78.4% of patients were seen by a stroke specialist within 24 hours of the event (Amarenco et al. 2016). Most patients received key urgent investigations before discharge and appropriate treatments were initiated. For example, 5.0% of patients received a new diagnosis of atrial fibrillation, of which 66.8% received anticoagulant therapy before discharge. Carotid stenosis of ≥50% was found in 15.5% of patients, of which 26.9% underwent carotid revascularization before discharge. The one-year estimate of risk of the primary outcome, a composite of death from cardiovascular causes, nonfatal stroke and nonfatal acute coronary syndrome, was 6.2% (95% CI 5.5-7.0 %). Estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. These estimates were much lower than those compared with historical cohorts and were attributed to the widespread establishment of TIA clinics. Rothwell et al. (2007) reported that patients who had immediate access to a TIA clinic (EXPRESS) had a significantly reduced risk of recurrent stroke (2.1% vs.10.3 %, p=0.0001), compared with an historical cohort who did not have immediate access to the same care. Patients with immediate access also received their prescriptions sooner (median of 1 vs. 20 days). Lavallée et al. (2007) reported the 90-day risk of stroke for all patients seen at their TIA-SOS clinic was lower than that predicted by their ABCD2 score (1.24% vs. 5.96%).
Detecting atrial fibrillation (AF) after a stroke or TIA is important since it is a major risk factor for subsequent stroke and, once identified, can be effectively treated. However, AF is under-diagnosed because it is frequently paroxysmal and asymptomatic, and patients do not routinely undergo prolonged screening. The low levels of monitoring were highlighted in a study authored by Edwards et al. (2016). The records of 17,398 consecutive patients presenting with first-ever stroke or TIA with motor or speech deficits, without a known history of AF in sinus rhythm, were reviewed and the utilization of ambulatory ECG monitoring within the first 90 days of the event was assessed. A total of 5,318 patients (30.6%) received at least 24-hour Holter monitoring within 30 days of the index event. The numbers associated with more prolonged Holter monitoring were lower; 2,253 patients (12.9%) and 25 patients (0.1%) underwent 48-hr and >60-hr monitoring, respectively within 90 days. Monitoring with event loop recording was conducted in 139 patients (0.8%) within 90 days. A meta-analysis conducted by Sposato et al. (2015) examined the use of outpatient cardiac monitoring following minor stroke or TIA in 4 distinct phases. The results from the studies that initiated investigations during the second ambulatory period (phase 4), using mobile cardiac outpatient telemetry (n=5), external loop recording (n=7) or implantable loop recording devices (n=7), reported an estimated 16.9% (95% CI 13.0% -21.2%) of patients were diagnosed with AF.
The results from four RCTs and numerous observational studies have demonstrated that prolonged post-stroke ECG monitoring using wearable or insertable devices is effective for improving the detection of paroxysmal AF (number needed to screen range from 8-14), with longer monitoring durations associated with an increased probability of AF detection. In the Event Monitor Belt for Recording Atrial Fibrillation after a Cerebral Ischemic Event (EMBRACE) trail (Gladstone et al. 2014), a 30-day ambulatory cardiac event monitor was found to be superior to repeat 24-hour Holter monitoring in identifying AF in 572 patients aged 52 to 96 years (mean=72.5 years) without known AF, who had sustained a cryptogenic ischemic stroke or TIA within the previous 6 months. Atrial fibrillation lasting ≥30 seconds was detected in 16.1% of patients, using the cardiac event monitor compared with 3.2% of patients in the Holter group (absolute difference, 12.9%; 95% CI 8.0 to 17.6; p<0.001; number needed to screen= 8). The cardiac event monitor was also more likely to identify cases of AF lasting longer than ≥2.5 minutes (9.9% vs. 2.5%, absolute difference, 7.4%, 95% CI, 3.4 to 11.3; p<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group (18.6% vs. 11.1%, p=0.01). Three-quarters of AF cases identified in the intervention group were detected within the first 2 weeks of monitoring. In a UK trial (Higgins et al. 2013) in which 100 patients with no history of AF and in sinus rhythm were randomized, a strategy of 7-day ECG monitoring in the acute phase post-stroke was found to be superior to standard care for the detection of paroxysmal AF (18% vs. 2%; p<0.05). Significantly more patients who received additional monitoring were started on anticoagulants.
The Finding Atrial Fibrillation in Stroke - Evaluation of Enhanced and Prolonged Holter Monitoring (FIND-AF) trial randomized 398 patients over age 60 years (average age 73 years) reported that a strategy of 10-day Holter monitoring started within the first week post stroke and repeated at 3 months and 6 months was superior to standard care, which consisted of an average of 73 hours of inpatient telemetry plus an average of 24 hours of Holter monitoring (Wachter et al. 2016). At 6 months, detection of AF was significantly higher in the prolonged monitoring group (13.5% vs. 4.5%; absolute difference 9%, 95% CI 3.5-14.6, p=0.002; NNS=11). Similar findings were reported in the Cryptogenic Stroke and Underlying AF (CRYSTAL-AF) trial (Sanna et al. 2014) when patients (mean age of 61.5 years) received long-term monitoring with an insertable cardiac monitor (ICM). At 6 months, the rate of detection of AF was significantly higher among patients assigned to the ICM group (8.9% vs. 1.4%, HR=6.4, 95% CI 1.9- 21.7, p<0.001), compared with those who received standard monitoring using ECG monitoring on a schedule at the discretion of their treating physician. Similar results were reported at 12 months (12.4% vs. 2.0%, HR=7.3, 95% CI 2.6- 20.8, p<0.001).
The clinical and cost-effectiveness of prolonged ECG monitoring are likely greater for patients with estimated good life expectancy and quality of life, and for those with excessive atrial ectopy, enlarged or poorly contracting left atrium, or elevated natriuretic peptide levels. While prolonged post-stroke ECG monitoring improves AF detection and may lead to a change in patient management from antiplatelet to anticoagulant therapy, there are notable limitations to the available evidence, as clinical trials have not been powered to determine the effect of prolonged ECG monitoring on the rate of recurrent stroke. Device-detected AF is often brief and subclinical and the minimum duration or burden of device-detected AF that warrants initiation of anticoagulant therapy remains uncertain; therefore, expert opinion varies widely.
Laboratory investigations and assessment of physiological variables as part of a patient’s initial evaluation provides important information for patient management. A small case control study found that maintenance of normal physiological variables within the first three days of stroke has a beneficial effect on outcomes post stroke (Langhorne et al. 2000). Blood biomarkers have been shown to correlate with cerebral lesion size and stroke severity (Kisialiou et al. 2012). Ferrari et al. (2010) found that hypertension, diabetes, possible etiology, acute infection and cardiac abnormalities were all independent predictors of deterioration following TIA or minor stroke, and recommended immediate diagnostic testing for their identification. Together, these findings suggest a complete evaluation of patients presenting with suspected stroke or TIA is beneficial for predicting risk of recurrent stroke and guiding patient management.