We previously analyzed five trials on ticagrelor/aspirin versus clopidogrel/aspirin in patients with minor stroke/ TIA in a network meta-analysis. We updated our search and identified 311 new citations with one study for inclusion: CHANCE2 enrolled patients with CYP2C19 loss-of-function alleles and randomized them to ticagrelor/aspirin or clopidogrel/aspirin. Pooling of CHANCE2 with the original studies could not be completed due to violation of NMA assumptions, due to significant inconsistency. This suggests patients with CYP2C19 loss-of-function alleles represent a subpopulation that is inherently different from the general stroke population in their antiplatelet response. Results from CHANCE-2 may not be generalizable without genotype testing.

Introduction: National guidelines (NICE, AHA) for management of Acute Cerebrovascular Syndrome (ACVS) in the Emergency Department (ED) recommend the use of ABCD2 score to risk stratify patients despite its poor specificity and low diagnostic accuracy. The SpecTRA project previously developed a clinical classifier for ACVS vs. Mimic derived from historical clinical data collected during a 5-year period at an outpatient stroke clinic (Victoria, BC). Here we present a prospective evaluation of the performance of our clinical classifier on prospectively collected ED patient data compared to the industry-standard ABCD2. Methods: The prospective cohort consisted of ED patients (N=555, Male=54%, Mean (SD) Age=68.7(15.5), ACVS=70%) enrolled between Jan 2014 and May 2015 at Victoria General Hospital (BC) and Foothills Medical Centre (Calgary, AB). ABCD2 and clinical classifier scores were calculated from clinical data from the ED. We compared the performance of the two classifiers using DeLong’s test of Dependent Receiver Operating Curves (ROC). In keeping with national guidelines, we used a score of 4 or more to assess sensitivity, specificity and accuracy (sens/spec and acc) of the ABCD2; for our clinical classifier, we used the cut point previously determined to maximize agreement between predictions and true class labels in the historical data. Results: Our new clinical classifier significantly outperformed the ABCD2 (z=2.44, p=0.015) with an AUC of 0.72, (95% CI: 0.68, 0.77) vs. 0.66 (0.61, 0.71). In terms of sens/spec and acc, our classifier achieved 0.78/0.55 with acc 71% compared to 0.75/0.46 with acc 66% for the ABCD2 (using the previously specified cut points). Conclusion: Our ACVS clinical classifier showed better performance than the ABCD2 score on a prospective sample of ED patients. The improved specificity of the clinical classifier relative to existing prognostic tools would reduce the number of non-ACVS patients referred for early treatment as well as conserve medical resources. Our ongoing multi-site study will evaluate the utility of the ACVS classifier embedded in a logic-enabled e-fillable form. This form will also provide risk-based thresholds guiding timely ordering of CTA as well as links to clinical treatment guidelines. Longer-term, the e-form and classifiers will be further enhanced to include plasma-based protein biomarker data.

Introduction: About 20% of TIAs are due to large vessel disease. Carotid stenosis >50% which is causing a TIA or stroke needs to be definitely managed quickly in order to benefit. Alternatively, dual antiplatelet therapy may be considered. The objective of this study was to determine high-risk diagnostic findings associated with symptomatic carotid disease in ED patients with TIA to indicate patients requiring urgent carotid imaging. Methods: We performed a prospective Canadian multicenter cohort study, at 13 academic sites, of ED patients with TIA or non-disabling stroke from 2006-2014. Study research nurses recorded imaging findings on standardized data collection forms from the final reports of all imaging tests ordered in the ED on prospectively enrolled patients by treating emergency physicians. Symptomatic carotid disease was defined as carotid stenosis 50-99% or carotid dissection and was adjudicated by stroke neurology to be the etiology of the index event. Patients were followed by medical review and telephone up to 90 days. Univariate analysis was conducted for investigation results with our primary outcome. Results: The cohort included 305 patients with and 5,277 without symptomatic carotid disease. Positive predictors of symptomatic carotid disease included platelet count over 400 x 109/L (15.3% vs 7.6%; p=0.0095), blood glucose >15 mmol/L (11.4% vs 4.4%; p<0.0001), CT evidence of acute infarction (9.8% vs 4.1%; p<0.0001), CT evidence of old infarction (35.7% vs 24.1%; p<0.0001), and CT evidence of any infarct (43.3% vs 26.7%; p<0.0001). There were no negative predictors of symptomatic carotid disease. Conclusion: High-risk investigation findings suggestive of symptomatic carotid disease in ED TIA patients include platelet count over 400 x 109/L, blood glucose >15 mmol/L, CT evidence of any infarction. Patients with any of these findings should be considered for rapid carotid imaging.

Introduction: TIAs precede about 30% of strokes, with 4-10% having a stroke within 90 days of their TIA. In patients with a TIA due to symptomatic carotid disease, diagnosis and treatment within 2 weeks has been shown to have much better outcomes, while delay beyond 12 weeks no longer reduces subsequent stroke risk. The objective of this study was to determine the clinical findings associated with symptomatic critical disease following an ED visit for TIA to indicate patients requiring prompt carotid imaging. Methods: We performed a prospective Canadian multicenter cohort study, at 13 academic sites, of ED patients with TIA or non-disabling stroke from 2006-2014. Treating ED physicians indicate clinical features on standardized data collection forms. Symptomatic carotid disease was carotid stenosis 50-99%, or carotid dissection, adjudicated by stroke neurology to be the etiology of the index event. Patients were followed by medical review and telephone up to 90 days. Univariate analysis was conducted for clinical features associated with patients who were eventually found to have symptomatic carotid disease as a cause for their TIA. Results: The cohort included 305 patients with and 5,277 without symptomatic carotid disease. Positive predictors of symptomatic carotid disease included older age (74.0 yrs vs 68.0 yrs p<0.0001), male sex (62.9% vs 47.9%; p<0.0001), history of weakness (63.3% vs 41.4%; p<0.0001), language disturbance (52.1% vs 40.0%; p<0.0001), weakness on physical exam (25.5% vs 17.1%; p=0.0002), history of hypertension (74.8% vs 59.5%; p<0.0001), and known history of carotid stenosis (18.9% vs 3.1%; p<0.0001). Negative predictors of symptomatic carotid disease included first ever TIA (56.8% vs 68.8%; p<0.0001), history of altered sensation (39.4% vs 45.8%; p=0.0322), lightheadedness (13.0% vs 22.4%; p=0.0002), and vertigo (3.6% vs 12.7%; p<0.0001). Conclusion: TIA patients with older age, male sex, weakness, language disturbance or history of carotid stenosis need to be promptly imaged to assess for symptomatic carotid disease.